Neuromodulation of the central nervous system for facial pain.

Neuromodulation of the central nervous system for facial pain - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Neurotherapeutics . 2026 Apr 11;23(3):e00902. doi: 10.1016/j.neurot.2026.e00902 Search in PMC Search in PubMed View in NLM Catalog Add to search Neuromodulation of the central nervous system for facial pain Jason Yuen Jason Yuen a Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, M5T 2S8, Canada Find articles by Jason Yuen a, ⁎ , Aaron Loh Aaron Loh a Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, M5T 2S8, Canada Find articles by Aaron Loh a , Ghazaleh Darmani Ghazaleh Darmani a Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, M5T 2S8, Canada Find articles by Ghazaleh Darmani a , Can Sarica Can Sarica a Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, M5T 2S8, Canada Find articles by Can Sarica a , Nikunj Patel Nikunj Patel b Division of Neurosurgery, Southmead Hospital, Bristol, BS10 5NB, United Kingdom Find articles by Nikunj Patel b , Andres M Lozano Andres M Lozano a Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, M5T 2S8, Canada Find articles by Andres M Lozano a, 1 , Mojgan Hodaie Mojgan Hodaie a Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, M5T 2S8, Canada Find articles by Mojgan Hodaie a, 1 Author information Article notes Copyright and License information a Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, M5T 2S8, Canada b Division of Neurosurgery, Southmead Hospital, Bristol, BS10 5NB, United Kingdom ⁎ Corresponding author. [email protected] 1 Co-senior authors. Received 2025 Dec 30; Revised 2026 Mar 26; Accepted 2026 Mar 26; Collection date 2026 Apr. © 2026 The Author(s) This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). PMC Copyright notice PMCID: PMC13092053  PMID: 41967178 Abstract Chronic craniofacial pain can lead to significant morbidity and reduced quality-of-life. Refractory pain subsequently leads to maladaptive changes within the central nervous system (CNS). It is logical to consider modulation of implicated neural networks to mitigate or reverse these changes in order to alleviate suffering. In this report, we reviewed the current literature in neuromodulation of CNS in facial pain treatment. We conducted PRISMA-compliant systematic review using MEDLINE and EMBASE databases. We included studies applying stimulation to the CNS to treat facial pain. Demographic data, design, duration, participants, clinical details, outcomes, adverse effects were extracted. Out of 1005 unique publications, 57 were included for analysis. Main techniques included were transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), motor cortex stimulation (MCS), deep brain stimulation (DBS), and spinal cord stimulation (SCS). For tDCS, rTMS, and MCS, the main stimulation target was primary motor cortex; while several different DBS targets (e.g., thalamic nuclei, anterior cingulate cortex, periaqueductal grey matter) were studied. While most studies showed improvement in Numeric Rating Scale for pain, values range widely from 11.1% in one MCS study to 90% in one rTMS study, with majority within 20–60%. There is heterogeneity across research designs, including patient selection, outcome measures, and follow-up. Standardized reporting framework is required to allow direct comparison between different modalities within subgroups of facial pain patients. Keywords: Craniofacial pain, Trigeminal neuralgia, Neuropathic pain, Repetitive transcranial magnetic stimulation, Motor cortex stimulation, Deep brain stimulation Graphical abstract Open in a new tab Introduction Chronic orofacial pain is highly disabling and leads to significant morbidity, with both serious physical and psychological sequalae. According to one study, craniofacial pain leads to a four-fold increase in functional problems such as difficulty chewing foods and a nine-fold increase in depression, compared to the general population [ 1 ]. Furthermore, it poses substantial costs to the healthcare system. One UK study estimated a cost of around £3000 (USD$4000) per year per patient due to prescription charges, travel and absenteeism [ 2 ]. It is estimated chronic orofacial pain can affect up to 11% of the population [ 3 ]. According to the International Classification of Headache Disorders edition 3 (ICHD-3) diagnostic criteria, facial pain can be classified into different subtypes [ 4 ]. On one hand, certain types of trigeminal neuralgia (TN) (ICHD-3 13.1.1) may be amenable to standard treatments in the form of medications, stereotactic radiosurgery, percutaneous rhizotomy, and/or microvascular decompression [ 5 ]. On the other hand, there are circumstances where patients may have a more chronic pain pattern, which is often resistant to these interventions. This can lead to severe morbidity and impact on quality of life [ 6 ]. This kind of “atypical facial pain” can be further classified into other forms of TN or trigeminal neuropathic pain [ 4 ]. In addition, after treatments, patients could develop severe numbness associated with pain, known as anesthesia dolorosa. These forms of facial pain syndromes also tend to be highly resistant to conventional treatments [ 7 ]. Peripheral nerve stimulation and peripheral field stimulation provide some relief in certain pain conditions but their effectiveness is variable [ 8 ]. There is imaging and physiological evidence that chronic pain can lead to structural and functional changes in the central nervous system (CNS). Maladaptive neuroplasticity, known as central sensitization plays a critical role in the propagation of the chronic pain, rendering peripheral interventions less effective than expected [ 5 , 9 ]. Therefore, attempts have been made to target the key areas involving the CNS (intracranial and spinal cord) structures to provide pain relief, via both non-invasive and invasive means. Detailed review of the neurocircuitry involved in chronic facial pain can be found in Refs. [ [10] , [11] , [12] ]. In brief, facial sensation (and hence nociception) is mediated by the sensory component of the trigeminal nerve, which consists of three branches (V1/V2/V3). The cell bodies are mostly in the trigeminal ganglion and project to second-order neurons in the two main trigeminal sensory nuclei - trigeminal main sensory nucleus and spinal trigeminal nucleus (which is further divided into three subnuclei – oralis, interpolaris, and caudalis). These nuclei then project further to structures in the higher levels such as the thalamus and other brainstem regions (e.g., reticular formation). Thalamic nuclei, such as the ventral posterior medial nucleus (VPM) and centromedian-parafascicularis nucleus of thalamus (CM-Pf), in turn, projects to various cortical regions. VPM primarily projects to the primary sensory cortex; whereas CM-Pf projects to primary sensory cortex, insular cortex, motor cortex, anterior cingulate cortex (ACC) and prefrontal cortex (PFC). ACC, in turn, projects to other cortical areas such as the PFC, basal ganglia, hypothalamus, and amygdala. In particular, CM-Pf, ACC and insular cortex are critical mediator of the affective and motivational response to pain [ 11 ]. Interspersed with this pathway is the pain modulation circuit. The descending pain modulation circuit aims to induce antinociception and is partly mediated by the amygdala, periaqueductal grey matter (PAG), locus coeruleus (within reticular activating system), and trigeminal nucleus caudalis. Modulation of some of these key nodes within the pain circuitry has been explored to manage intractable facial pain. In the current article, we will review clinical studies that utilized different types of neuromodulation in the CNS to treat facial pain. Methods A literature review was performed using key words in the Medline and EMBASE databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework [ 13 ]. Review was registered with Open Science Framework [ 14 ]. Entries up to 24 September 2025 were included. To capture the breadth of facial pain conditions and interventions, key words employed included a combination of: “facial pain”, “trigeminal neuralgia”, “trigeminal neuropathy”, “Tic Douloureux”, “anesthesia dolorosa”, “post-herpetic neuralgia”, “post-stroke pain”, “post-stroke neuralgia”, “stimulation”, “modulation”, “neuromodulation”, “lesioning”, “motor cortex stimulation”, “electrical”, “direct current”, “magnetic”, “radiofrequency”, “deep brain stimulation”, “ultrasound”, “spinal cord stimulation”. After the search was performed, duplicates studies were removed using bibliographic software EndNote™ 21.5 (Clarivate, Philadelphia, PA). The remaining articles were screened by title and abstract for relevance. Then, articles progressing to full-text review were screened based on the pre-specified inclusion and exclusion criteria (see below). Each title and abstract were independently examined by two authors (J. Y. and A. Loh) to identify eligible studies, with any conflicts resolved by a blinded third reviewer (G.D.). Full texts were then reviewed. Data extracted included participant demographics (age, sex), indication for treatment, mean follow-up periods, pre- and post-treatment pain score (Numeric Rating Scale for pain (NRS) or Visual Analogue Scale (VAS)), percentage changes in pain score, percentage of “responders”, stimulation parameters, adverse effects from treatment. Inclusion criteria included: articles in English language, invasive and non-invasive modalities, human studies, participants with and without prior treatments, classical and atypical trigeminal pain, post-herpetic pain, post-stroke pain mainly involving the face. Exclusion criteria included: review articles, conference abstracts, studies of healthy individuals only, lesioning modalities. In addition, studies focusing on: primary headaches (e.g., migraine, cluster headache), predominant occipital neuralgia pain, burning mouth syndrome, myofascial pain syndrome, fibromyalgia, predominant neck pain, temporomandibular joint (TMJ) or dental disorders, post-stroke pain that is hemibody in distribution or does not involve the face, lesional causes that are amenable to surgical resection, peripheral stimulation only (e.g., stimulation of sphenopalatine or trigeminal ganglion, stimulation of trigeminal nerve or occipital nerve, transcutaneous electric nerve stimulation (TENS), vagal nerve stimulation (VNS)), peripheral injections (e.g., botulinum toxin), trigeminal tractotomy-nucleotomy and dorsal root entry zone lesioning were excluded. We have excluded single case reports ( i.e. , n < 2). For motor cortex stimulation (MCS) studies, we have further excluded studies with less than 15 cases and those that do not include facial or trigeminal pain cases. The main reason is that it is a well-studied treatment modality in treating facial pain and there is a large volume of studies in this field, therefore we restricted our search to higher quality evidence from centers with larger volume. Results The search yielded 1005 unique publications, and 57 articles were included in this review after titles, abstracts, and full text were screened ( Fig. 1 ). Interventions were categorized into Transcranial direct current stimulation (tDCS), Repetitive transcranial magnetic stimulation (rTMS), MCS, Deep brain stimulation (DBS), Spinal cord stimulation (SCS), and other modalities, which will be described in more detail below ( Table 1 ). The stimulation targets are summarized in Fig. 2 . Fig. 1. Open in a new tab Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart of literature search. Other sources include extra publications that were harvested through relevant review articles. Table 1. Summary of studies using central neuromodulatory techniques for facial pain treatment. ACC, anterior cingulate cortex; AN, anesthesia dolorosa/trigeminal deafferentation pain; BMP, burning mouth syndrome; BNI, Barrow Neurological Institute pain scale; CL, central lateral nucleus of thalamus; CM, centromedian nucleus of thalamus; CMJ, cervicomedullary junction; CP, central pain; CPSP, chronic post-surgical/-traumatic pain of the peripheral nervous system (including plexus avulsion); CRPS, chronic regional pain syndrome; DBS, deep brain stimulation; DE, dental extraction (orofacial pain); FC, functional connectivity; GK, gamma knife; IPG, implantable pulse generator; ITI, intertrain interval; LBP, low back pain; M1, primary motor cortex; MCS, motor cortex stimulation; MS, multiple sclerosis; MVD, microvascular decompression; NA, not available; nBR, nociceptive blink reflex; NRS, Numeric Rating Scale; ON, occipital pain/neuralgia; PAG, periaquectal grey; Pf, parafascicularis nucleus of thalamus; PHP, post-herpetic pain; PLP, phantom limb pain; PREP, pain-related evoked potentials; PSP, post-stroke pain/vascular insufficiency; PSPS, Persistent Spinal Pain Syndrome; PVG, peri-ventricular grey; radiofrequency, rhizotomy, rTMS, repetitive transcranial magnetic stimulation; SCI, spinal cord injury; SCS, spinal cord stimulation; SOL, space-occupying lesion (tumor/vascular lesions); SSC, somatosensory cortex; tDCS, transcranial direct current stimulation; TNP, trigeminal neuropathic pain; TUS, transcranial ultrasound; VAS, visual analogue scale; VPL, ventral posterior lateral nucleus of thalamus; VPM, ventral posterior medial nucleus of thalamus. Reference Modality Indications Age, y Gender ratio, M:F Mean follow-up, months Mean pre-operative NRS Mean post-operative NRS Mean changes in NRS, % Percentage of responders, % Stimulation parameters Side-effects and Complications Extra note Antal 2010 [ 16 ] tDCS Target: M1 (hand area) 8 Back pain 5 TN/TNP 3 Fibromyalgia 4 Arthrosis 1 PSP 1 PLP 1 Polyneuropathy [ 23 ] 57.0 ± 10.5 6:17 4 weeks Normalized VAS [ 1 ] to both Normalized VAS Stim.: 0.82 ± 0.07 Sham: 0.97 ± 0.06 Stim.: 18 Sham: 3 (double-blinded) 4 responders (reduction of 30% or more on VAS) in tDCS group; 1 in sham group at follow-up 20 min; 1 mA; anodal; 5 consecutive days Stim. vs Sham (randomized; cross-over in 13) 6 had tDCS only and 4 had sham only Main side-effect after stim. were fatigue (6 tDCS, 12 sham) and headache (7 tDCS, 6 sham) Bae 2014 [ 17 ] tDCS Target: M1 14 PSP Including 5 Hemibody (+face) 3 Hemibody (-face) 3 upper limb 1 lower limb 2 face Stim. 52.3 ± 2.8 Sham 51.1 ± 3.1 7:7 (similar between tDCS and sham) 3 weeks tDCS: 4.3 ± 1.1 Sham: 4.3 ± 0.8 tDCS: 3.1 ± 0.9 Sham: 4.1 ± 1.2 tDCS: 28 Sham: 5 NA 20 min; 2 mA; anodal; 3 days/week for 3 weeks Stim. (7/14) vs Sham (7/14) None reported Note: tDCS also improves threshold temperatures for sense of cold or heat and pain Hagenacker 2014 [ 18 ] tDCS Target: M1 10 TN (classic) 62 [49–82] 5:5 2 weeks tDCS: 6.7 ± 1.3 Sham: 7.2 ± 1.2 tDCS: 5.5 ± 2.3 Sham: 7.8 ± 1.8 tDCS 19 ± 29% Sham 11 ± 30.8% (double-blinded) NA Daily stim. for 20 min over 2 weeks Anodal (1 mA) Stim. vs Sham (randomized; double-blind cross-over) None reported Note: No change in attack frequency despite NRS improvement; improvement is also attributable to improvement among those with purely paroxysmal (6/10) but not those with concomitant persistent pain (4/10) PREP showed increased N2 latency and decreased peak-to-peak amplitude post-tDCS Fricova 2019 [ 19 ] % tDCS Target: dorsolateral prefrontal cortex 19 “secondary TN” 15 responded to questionnaires NA NA 6 mon but outcome reported at 2 weeks tDCS: 5.9 ± 0.3 Sham: 5.1 ± 0.4 tDCS: 4.6 ± 0.4 (22% improvement) Sham: 5.5 ± 0.5 (8% deterioration) tDCS: 22% improvement Sham: 8% deterioration NA 1 session per day for 5 consecutive days Stim. vs Sham (crossover) 1 mA, 20 min stimulation Cathode and anode placed on the affected temporal area None reported Note: At 2 weeks, 62.5% of patients reported that tDCS reduced pain perception by 53.7 ± 31.5% 12.5 % reported that the pain was unchanged 25% reported that the pain had worsened by 53.3 ± 3.33% 4/15 reported improved Beck depression inventory 9/15 also reported improved Beck anxiety inventory Babakhani 2022 [ 20 ] tDCS Targets: contralateral SSC (cathode); contralateral M1 (anode) 6 TN 3/6 inhibitory/cathodic and 3/6 excitatory/anodic stimulation NA NA 1 week post-treatment 8.4 (for both) Cathode 1.8 Anode 1.4 Cathode 79 Anode 83 NA 5 sessions per patient; 2 mA; 20 min duration with 30 s fade in/out; 1-day interval between sessions None reported Note: imaging study revealed anodic tDCS attenuating ipsilateral caudate, globus pallidus, SSC, and the contralateral globus pallidus; cathodic tDCS attenuated thalamus and globus pallidus bilaterally, and the SSC and ACC contralaterally, as well as changes in relevant sensory fibers Lefaucheur 2001 (23) rTMS Target: M1 (representation of painful area) 7 TN (with previous surgery) 7 PSP [ 14 ] 57.2 [32–80] 6:8 12 days TN group rTMS 5.8 ± 0.7 Sham 6.0 ± 0.5 TN group rTMS 6.9 ± 1.3 Sham 7.9 ± 0.5 TN group rTMS 17% increase Sham 32% increase 4 patients in each of TN and PSP (pain relief ≥30%) 20-min session 20 trains of 5 s in duration (ITI 55); 10 Hz; 80% motor threshold; using a ‘real’ or a ‘sham’ coil; at least 3 weeks apart None reported Note: Significant reduction in NRS in rTMS group compared to sham observed from days 1 to 8 but not beyond Lefaucheur 2004 [ 27 ] rTMS Target: M1 (hand area) 12 thalamic stroke 12 brainstem stroke (2 with facial pain) 12 SCI 12 CSPS 12 TN (failure of surgery) [ 60 ] 54.6 [27–79] 28:32 Same session 6.8 ± 0.2 (same for both rTMS and sham) rTMS 5.4 ± 0.3 Sham 6.2 ± 0.3 rTMS 22.9 Sham 7.8 (facial pain group: 36.9 ± 10.2) 26.7 20 trains of 5 s in duration (ITI 55); 10 Hz; 80% motor threshold; using a ‘real’ or a ‘sham’ coil; at least 3 weeks apart None reported Note: better results were obtained for facial pain, although stimulation was targeted on the hand area Khedr 2005 [ 28 ] rTMS Target: M1 (hand area) 24 TN 24 PSP [ 48 ] TN 51.5 ± 10.7 PSP 52.3 ± 10.3 TN 8:16 PSP 14:10 15 days after last session TN rTMS: 8.5 ± 0.4 Sham: 8.0 ± 0.2 TN rTMS: 4.8 ± 0.6 Sham: 6.5 ± 0.7 TN rTMS: 44 Sham: 19 TN rTMS: 57.1 Sham: 20 Defined as ≥40% improvement 14 from each group received 10 min rTMS over the hand area of motor cortex (20 Hz, 10610s trains, intensity 80% of motor threshold) every day for five consecutive days. The remaining patients received sham stimulation None reported Lefaucheur 2006 [ 24 ] rTMS Target: M1 (representation of painful area vs hand area) 7 TN with previous surgery 4 PSP 4 post-dental surgery 3 post-facial surgery [ 18 ] 56.8 [36–79] 3:15 1 week after each treatment 7.9 ± 1.2 Hand stim. 52.7 ± 5.9 Face stim. 71.2 ± 5.3 27% improvement after hand area rTMS and 11% after face rTMS (patient-blinded) 8/18 after hand stim and 3/18 after face stim (defined as ≥30% pain relief) 10 Hz Facial pain group: 2 different sessions of rTMS, targeting the face or hand motor cortical area (separated by ≥ 4 weeks) 20 trains of 10 s duration (ITI 50 s); 10 Hz; 90% motor threshold None reported Note: rTMS was more effective when the stimulation was applied to an area adjacent to the cortical representation of the painful zone rather than to the motor cortical area corresponding to the painful zone itself Saitoh 2006 [ 126 ] rTMS Target: M1 12 PSP 2 Spinal cord lesions 1 root avulsion 3 TNP 2 peripheral nerve injuries [ 20 ] [28–72] 14:6 Same session NA NA NA 50%) showed significant (≥30% improvement) reductions in pain on the VAS with M1 stimulation Figure-of-8 coil 10 trains of 5 Hz rTMS for 10 s (50 s resting interval) applied to M1, S1, preM and SMA areas at random A total of 500 stimuli were applied once in 2 days and the stimulation was done twice for each target None reported 5 went on to receive MCS (see below) Fricova 2013 [ 127 ] rTMS Target: M1 17 secondary TN 6 typical orofacial pain (no clear organic cause) [ 23 ] 50.7 [33–65] 16:7 2 weeks after treatments rTMS 5.5 ± 0.4 Sham 5.7 ± 0.5 rTMS 4.1 ± 0.7 Sham 5.9 ± 0.8 rTMS 26 Sham 4 (increase) (double-blinded) NA 20 Hz; 1 session/day over 5 consecutive days 720 pulses/session 2–36x trains ITI 1.9s 95% of motor threshold None reported Note: Authors also compared to a cohort receiving 10 Hz (n = 36), which had less improvement compared to the 20 Hz group (not significant at 2 weeks) Hodaj 2015 [ 30 ] rTMS Target: M1 21 TNP 19 cluster headache 15 atypical TN [ 55 ] Cluster headache 45.6 ± 13.4 Others 66.1 ± 11.8 30:25 180 days Permanent pain 5.2 ± 1.6 Paroxysmal pain 8.6 ± 1.5 Permanent pain 2.0 ± 1.5 Paroxysmal pain 0.9 ± 1.6 Permanent pain 62 Paroxysmal pain 90 40% at Day 180 (pain score decrease ≥30%) “Induction phase” of 1 daily rTMS session for 5 days per week during 2 consecutive weeks, followed by a “maintenance phase” of 2 sessions for 1 week, then 1 session in weeks 4 and 6, and a monthly session for the next 5 mon 10 Hz; 80% resting motor threshold; 40 trains of 5s with ITI 25s (2000 pulses in 20 min) (22 pt); duration shortened to 10 min: 20 trains of 10s, ITI 20s (18 pt); 40 trains of 5s with ITI 10s (15 pt) None reported Note: number of daily painful attacks reduced from 5.6 ± 3.1 to 0.3 ± 0.5 Ayache 2016 [ 128 ] rTMS Target: M1 22 CSPS 17 PSP 16 TNP (iatrogenic) 11 SCI [ 66 ] 51.2 ± 11.5 [18–76] 32:34 1 week after each stim. session No statistically significant improvement in facial pain across all modalities but improved upper and lower limb pain patients with rTMS Sham vs non-navigated rTMS of hand M1 vs navigated rTMS of specific pain region 3 sessions performed 3 weeks apart 10 Hz None reported Note: Pain relief last for 1 week after navigated rTMS Lawson McLean 2018 [ 29 ] rTMS Target: M1 33 Atypical facial pain 5 PSP 4 neuropathic lower limb pain 3 PLP 5 Others [ 50 ] 2 atypical facial pain patients dropped out 56.3 [32–78] 23:27 6 weeks Responder 6.36 [2–10] Non-responder 6.60 [2–9] Responder 2.86 [1–7] Non-responder 6.45 [2–9] Responder 55.0 Non-responder 2.3 28/48 patients (22/31 facial pain) (anyone with pain reduction was defined as a “responder”) Over 9 consecutive days with 2 days between 4th and 5th treatment, so total duration of 11 days 10 Hz; 80% of motor threshold 10 trains, each lasting 10s, with an ITI of 50s None reported Note: Diagnosis, anatomical localization ( e.g. , facial pain) and duration ( e.g. , < 5 years) of pain symptoms were found to predict response to rTMS Hodaj 2020 [ 25 ] rTMS Target: M1 (representation of painful region) 26 Orofacial pain - SOL of trigeminal nerve or nucleus [ 8 ] - Sec to rhizotomy [ 2 ] - Sec to MVD [ 2 ], - Sec to neurinoma surgery [ 1 ] - PHP [ 2 ] - MS [ 1 ] - Unknown/idiopathic causes [ 12 ] 18 Pudendal neuralgia 13 neuropathic limb pain [ 57 ] 62.2 ± 15.0 21:36 After maintenance phase (day 180) Overall Permanent 6.0 + 1.9 Paroxysmal 8.4 ± 1.4 Responder Permanent 2.9 ± 2.3 Paroxysmal 3.8 ± 2.8 N/A 47 (27 pt; from baseline to end of maintenance phase) (pain intensity dropped by ≤ 30%) ‘‘Induction phase” of 12 daily rTMS sessions for 3 weeks, followed by ‘‘maintenance phase” of bi-monthly sessions for the next 5 months 10 Hz; 80% of the motor threshold Each session consisted of 40 trains of 5s with ITI 25s for a total of 2000 pulses in 20 min None reported Note: Anxiety, depressive symptoms and quality of life also improved. 10 patients dropped out due to recurrence of significant pain; 2 patients were lost to follow-up Poydasheva 2021 [ 129 ] rTMS Target: M1 17 TN Med 56 [38–65] 3:14 Immediately after treatments NA NA NA “Half” of patients (peak pain dropped by ≤ 30%) 10 sessions (1 per weekday over 2 weeks) 10 Hz; 90% of motor threshold Train duration 4s, ITI 26s; 1600 pulses/session Target abductor pollicis brevis None reported Note: Radiological findings were also studied, e.g. , positive correlation between reduction in pain intensity and grey matter (GM) volume in caudate nuclei, cerebellar hemispheres and postcentral gyrus contralateral to pain side Säisänen 2022 [ 26 ] rTMS Target: M1 (lower facial representation) 14 post-traumatic TNP 4 idiopathic TN 2 secondary TN [ 20 ] 57.7 ± 15.7 [35–82] 7:13 2 weeks after each treatment 20 Hz 7.3 ± 1.7 10 Hz 6.9 ± 1.3 20 Hz 5.6 ± 2.8 10 Hz 5.8 ± 2.3 20 Hz 22 10 Hz 16 Straight after treatment: 4/10 of each group were responders (but there was some deviation from the protocol) (max pain relief ≥30%) Randomized to 2 distinct 5-day rTMS sessions then crossed over (separated by 6 weeks) A) 10 Hz (2400 pulses, trains of 6 s, ITI 24 s, total duration 20 min); 12000 pulses weekly or B) 20 Hz (3600 pulses, trains of 4 s, ITI 46 s, total duration 37 min); 18000 pulses weekly Tiredness [ 3 ], headache [ 1 ], dizziness [ 2 ], pain in the head (eye, ear, cheek bone, lower jaw, temporal, parietal regions) [ 6 ], nausea [ 1 ], poor sleep [ 1 ], ophthalmic branch tickling [ 1 ], twitching of hand [ 1 ], tingling in hand [ 1 ], and tightness in the chest/crushing chest pain [ 1 ] Note: no significant difference in effect was found between the two protocols Thomas 2025 [ 33 ] rTMS Target: M1 Central 84 PSP 15 SCI (6 syrinx) 8 MS 6 CSPS 5 Oncology 5 “Infarct” 10 others 13 unknown Peripheral 19 CSPS 8 TN 6 Neuropathy 4 Oncology 3 PHP 6 Others (193) Bilateral pain in 12 participants 56.2 ± 13.6 102:91 2.2 ± 2.5 years (max 10 years 4 mon) but outcome reported was after 4 treatments 6.3 + 2.1 NA After 4 sessions, average improvement was 27.2 ± 28.0% 42% (pain relief ≥30%) 20 Hz, 80% motor threshold, 20 trains of 80 pulses per train, 84s ITI and 1600 pulses/session At least 4 consecutive sessions at the beginning None reported Note: success was higher with central neuropathic pain compared to peripheral cause (OR = 2.03[1.04;4.00]) Good rTMS response was found to have good correlation with epidural MCS success Nuti 2005 [ 130 ] MCS (epidural – 29; subdural – 2) 22 CP 4 SCI 4 CPSP 1 HI [ 31 ] 52.7 ± 12.2 18:13 49 8.5 5.7 (averaged over time) 32.4 52 Voltage N/A; 60–330 micro-s; 30–80 Hz 8 focal seizures; 1 infection; 2 surgical wound healing issues Pirotte 2005 [ 131 , 132 ] MCS (epidural) 6 PSP 4 TN 2 SS 2 CPSP 2 AMP 1 MS 1 PRP [ 18 ] 55.6 [33–73] 8:10 29.8 7.5 ± 0.6 3.7 ± 3.1 50.6 ± 41.3 61.1 1–5 V; 100 micro-s; 40 Hz 1 seizure and 2 infections Note: Performed with intraoperative cortical mapping and fMRI Rasche 2006 [ 133 ] a MCS (epidural) 10 TN 7 CP [ 17 ] 65.1 ± 8.4 4:13 43.2 8.5 ± 0.8 6.4 ± 2.5 24.8 ± 26.7 47.1 3.5–6 V; 210–360 micro-s; 50–85 Hz 7 intra-operative seizures; 1 infection; 1 speech arrest for 3 months Saitoh 2006 [ 126 ] MCS (18 subdural; 11 intra-sulcus) 16 PSP 6 CPSP 3 PLP 2 SCI 1 TNP 1 Pons injury [ 29 ] [28–76] 25:4 NA NA NA NA 64% of intra-sulcal MCS showed “good or excellent results” NA NA Lefaucheur 2009 [ 134 ] MCS (epidural) 6 CPSP 3 TN 3 NF1 1 SOL 1 PLP 1 PHP 1 DE [ 16 ] 49.4 ± 17.9 6:10 12 7.4 ± 1.3 3.5 ± 2.7 48 60 Randomized study 1.5–5 V; 60 micro-s; 40–50 Hz 1 patient fell post-op with rib fracture and pneumothorax – stimulation not turned on Nguyen 2009 [ 135 ] MCS (epidural) 35 CP 33 TN 23 CPSP 9 SCI [ 100 ] 55 [21–84] 57:43 89 [29–170] CP 8.3 TN 8.4 Others N/A CP 3.9 TN 3.6 Others N/A CP 53.1 TN 57.0 69 1–3.5 V; 60–150 micro-s; 25–60 Hz 3 infections; 1 skin ulceration; 1 stroke; 2 removal due to poor response; 1 focal seizure Fagundes-Pereyra 2010 [ 136 ] MCS (epidural) 13 CPSP 5 PSP 3 PLP 2 TBI 1 TN 1 SOL 1 MS 1 SCI [ 27 ] 46.8 ± 12.6 22:6 29.1 ± 24.6 7.8 ± 1.5 N/A 51.9 ± 24.7 55.6 2–5.3 V; 60–210 micro-s; 45–130 Hz 2 infection (IPG site); 2 focal seizure; 1 scar dehiscence; Maarawi 2013 [ 137 ] MCS (epidural) 10 PSP 4 CPSP 1 SCI [ 15 ] 52.6 ± 11.3 11:4 7 7 ± 0.73 (continuous pain); 8.8 ± 0.69 (paroxysmal pain) N/A 39.3 ± 23.7 40 0.5–5 V, 180 micro-s, 35–45 Hz No adverse events mentioned Follow-up is 57.1 ± 49.7 months André-Obadia 2014 [ 138 ] MCS (epidural) 11 PSP 4 TN 3 CPSP 2 SCI [ 20 ] 54.3 ± 9.7 11:9 73.2 ± 31.2 8.4 (s d. unclear) 6.0 (s d. unclear) 28.9 N/A 1.5–4.5 V; 60 micro-s; 25–50 Hz No adverse events mentioned Delavallée 2014 [ 139 ] MCS (subdural) 7 TN 3 PSP 6 CPSP 1 PLP 1 CRPS [ 18 ] 63 [11–91] 12:6 106 [40–160] 8.8 ± 0.7 2.8 ± 2.8 66.8 ± 33.6 81.3 1–6 V; 90–210 micro-s; 45–80 Hz 4 partial seizures during trial; 4 infections (removed and reimplanted later – 1 had to be done epidurally due to scarring) Isagulyan 2015 [ 140 ] MCS (epidural) 2 PLP 6 CPSP 4 PSP 3 SCI 3 TNP/MS 1 MS alone [ 19 ] 52 ± 12 [26–74] 10:9 49.3 [3–96] 7 ± 0.4 4.5 ± 0.4 33 [25–66] 73.7 1.0–5.5 V; 60–210 micro-s; 20–50 Hz 2 infections but no neurological deficits Slotty 2015 [ 141 ] MCS (epidural) 11 PSP 4 CPSP 4 SCI 2 TNP 2 CRPS [ 23 ] 53.0 ± 16.5 11:12 39.1 ± 19.9 7.8 ± 1.3 6.9 ± 2.0 11.1 ± 23.2 13.0 Stim. parameters N/A 3 focal motor seizure during trial stim.; 9 patients had explanation due to loss of treatment effect 2 patients underwent CM/Pf DBS afterwards Kolodziej [ 142 ] MCS (epidural) 8 PSP 6 SOL 2 CPSP 2 PHP 1 MS 1 TN [ 20 ] 59.8 [31–79] 9:11 [6m-6yrs] NA 11 patients attained almost complete/complete relief NA NA 1.3–7 V; 60–180 micro-s; 25–55 Hz 1 (5%) epidural hematoma that did not require surgery; 2 required re-operation after 1 yr due to loss of improvement; 1 cable breakage after trauma; 1 wound infection requiring explantation and re-implantation Rasche 2016 [ 143 ] MCS (epidural) TNP 11 SOL 11 DE 12 CPSP 2 N/A [ 36 ] 52.5 [25–82] 13:23 67.2 8.1 ± 1.7 5.0 ± 1.3 (only among responders) 45.8 ± 12.7 72 (30% rather than 40% reduction was used as threshold) 0.5–5 V; 200–450 micro-s; 20–50 Hz 4 wound infections; 2 lead breakages (all requiring revision surgeries); 1 focal seizure (despite MCS inactivation – explanted) Zhang 2017 [ 144 ] MCS (9 subdural; 7 epidural) 16 PSP (at least 5 with facial involvement) 59.9 ± 7.8 8:8 28.2 ± 10.7 8.0 ± 0.7 5.3 ± 2.4 33.7 ± 28.6 50 3.5–7 V; 210–300 micro-s; 30–50 Hz 2 intra-operative seizures; 1 subdural effusion (treated with trepanation and drainage); 1 electrode shift (adjusted) Henssen 2018 [ 145 ] MCS (epidural) 7 PSP 6 TN 2 CPSP 2 BMS 1 PLP [ 18 ] 59.0 ± 7.3 8:10 36 8.9 ± 1.1 5.3 ± 2.5 37.7 ± 26.8 38.9 1.5–5 V; 60–120 micro-s; 40–60 Hz 3 infections (removal of implants); 1 temporary seizures; 1 IPG malfunction Hamani 2021 [ 146 ] MCS (epidural) 6 CPSP 4 PSP 3 TN 3 PLP 2 CRPS [ 18 ] 49.6 ± 12.5 14:4 16 8.4 ± 1.2 6 (open label phase) 31.8 (open label phase) 39 b Voltage titrated to 80% of MEP (with pre-op rTMS); 90 micro-s; 50 Hz 1 infection requiring removal of system; 1 pseudo-seizure; 1 seizure; 6 discomfort neck; 1 tethered extension; 3 incision hyperemia Yuen 2024 [ 32 ] MCS (subdural) 29 TN 9 CPSP 3 PLP 2 PHP 3 others [ 46 ] 56.2 ± 12.5 13:33 57.2 ± 41.9 8.2 ± 1.8 3.5 ± 2.9 57.3 67 1.5 V–8 V (and 1 with 0.1 V); 60–578 ms; 2–130 Hz 5 infections with 4 requiring system removal; 22 seizures but most self-limiting; 3 epidural/subdural hematomas; 1 CSF leak Hosobuchi 1973 [ 113 ] DBS Target: VPM 5 AD (post-rhizotomy) 54.4 ± 13.8 2:3 [3–24]m and one electrode was externalized at the time of publication NA NA NA 4 pain-free; 1 continued to experience pain despite paresthesia (implant removed) 0.75–1.5 mA 0.5–4.5 V 0.4 ms 100–125 Hz None noted Note: all patients had induced paresthesia Siegfried 1982 [ 147 ] DBS Target: VPM 10 PHP (9 V1 and 1 in neck) 70.7 ± 5.5 [59–78] 3:7 11.8 ± 3.6 [8–17] NA NA NA 5 “excellent” (medication-free),3 “good” (on anti-depressant but no pain medications), 2 “poor” 33–195 Hz Duration per stim. 2–15 min, 1–8 times/day 1 had “psycho-organic syndrome” Levy 1987 [ 114 ] DBS Target: VPL/VPM (deafferentation); PAG/PVG (nociceptive) 1) Deafferentation pain: 25 thalamic pain 16 peripheral neuropathy 12 AD 11 paraplegic pain 5 post-cordotomy 5 PLP 4 thoracic neuralgia 6 Others [ 84 ] 2) Nociceptive pain: 6 cancer pain 51 LBP [ 57 ] (overall 141) 51.2 1) 52.0 2) 49.9 NA 6.8 [2–14] yrs NA NA NA 30% (deafferentation) and 32% (nociceptive) with long-term success Success defined as regular use of stimulator AD and paraplegic pain did not respond as well PAG/PVG 1–5 V, 10 ± 5 Hz, VPM/VPL 3–8 V, 20–100 Hz Wound infection (12.1%), erosion of hardware (7.1%), foreign body reaction (5.0%), intracranial hemorrhage (3.5%), psychosis (2.1%), death (0.7%) 8 patients had persistent headache 8.5% had hemi- or monoparesis, 7.8% had confusion Also other less common complications (see paper) Kumar 1997 [ 148 ] DBS Target: PVG (49)/sensory thalamus or posterior limb of internal capsule [ 14 ]/PVG + sensory thalamus [ 3 ] 43 PSPS 6 with peripheral neuropathy or radiculopathy 5 thalamic pain 4 TNP 3 SCI 3 PHP 2 CRPS 1 PLP 1 with carcinoma pain (68–53 had IPG implantation) 51.3 [30–80] 54:14 78 [6–170] NA NA NA “Effective pain control” (>50% pain relief) in 42/68 of initially referred patients (62%) Note: Patients with PSPS, TNP (4/4 had success), and peripheral neuropathy fared better; whereas those with thalamic pain, spinal cord injury, and PHP did worse Bipolar configuration for all patients PVG: 25–50 Hz, 1–5 V, 0.1–0.5 ms Sensory thalamus: 50–100 Hz, 2–8 V, 0.2–0.8 ms 4 infections; 2 fracture electrodes; 2 hardware malfunction; 2 seizures; 1 electrical leak; 2 blurred vision with stimulation; 1 intracerebral hematoma; 15 headache-like pain 6 patients received dual functioning system due to development of tolerance Note: posterior limb of internal capsule was used for those with thalamic pain secondary to a large infarct in VPL Owen 2007 [ 92 ] – likely overlaps with [ 149 ] DBS Target: PVG/PAG [ 18 ], VPL [ 4 ], PVG + thalamus [ 9 ], hypothalamus [ 1 ] 18 PSP 12 PLP 3 AD 3 SCI 1 MS 1 malignancy 1 PHP 8 Others (47–38 had IPG implantation with 6 lost to follow-up so only 32 included in analysis) 9 failed trial (6 PSP, 2 SCI, 1 other) 50 [24–76] 30:17 44.5 [1–76] 8.13 ± 1.23 3.93 ± 2.15 52 ± 27 [14–100] 50% (≥50% pain relief) PVG: 2.4 [0.8–4.5] V; 257 [120–450]ms, 22 [5–30] Hz VPL: 2.4 [0.7–4.4] V, 182 [60–400] ms; 26 [10–50] Hz Most effective for PLP, head pain and AD 2 infections; 1 lead fracture Note: PVG stimulation alone was optimal in 17 patients (53%), whilst a PVG + thalamic stimulation produced the greatest analgesia in 11 patients (34%) Thalamic stimulation alone was optimal in 4 patients (13%). DBS PVG alone was associated with the highest degree of pain alleviation (mean improvement of 59%) ≥50% improvement in 66% Franzini 2010 [ 39 ] – overlaps with [ [150] , [151] , [152] ] DBS Target: Posterior Hypothalamus 1) 5 TN from MS 2) 3 TNP [ 8 ] 1) 56 [49–65] 2) 51.3 [47–55] 1) 3:2 2) 2:1 1) 41 [11–51] 2) 4 1) BNI V in all 5 patients 2) NA 1) 4 BNI IIIa and 1 BNI I 2) NA 1) NA 2) NA 1) 100 2) 0 1) 41 2) 180 Hz, 60 ms, and 1.3 V (mean) In 1), 3 had recurrent pain and underwent RF rhizotomy Amplitudes beyond 3 V induced dizziness and oculomotor symptoms 1 small intraventricular hemorrhage was noted in the overall case series (including non-facial pain patients) Sims-Williams 2016 [ 153 ] DBS Target: PAG + CM-Pf 3 AN 44.3 ± 6.7 [31–52] 1:2 Patients had 18.7 ± 8.0 of DBS time but assessment was done at the same setting PAG 5.5 ± 1.3 Cm-Pf 6.7 ± 0.7 Dual 6.2 ± 0.2 PAG 2.4 ± 0.9 Cm-Pf 2.2 ± 0.7 Dual 1.7 ± 0.7 PAG 56 Cm-Pf 67 Dual 73 NA 3 paradigms PAG only CM-Pf only Dual Transient dizziness (CM-Pf) Note: only short periods are allowed for NRS assessment between settings Boccard 2017 [ 120 , 154 ] DBS Target: ACC 9 PSP – 1 affecting face specifically 6 PSPS 5 CSPS 2 SCI 2 Others (24–22 had IPG implantation) 9 patients previously had PVG or VPL DBS 49.1 [21–72] 19:5 12/22 had follow-up of av. 38.9 mon [24–65] These were included in NRS analysis 8 [5–10] At 6 months, 4.3 [0–10] At 1 year, 4.9 [0–9.5] At 36 months, 7.1 [3–9.5] At 6 months, 60.3% [0 to −100] At 1 year, 43.4% [0 to −100] 45.5% reported “substantial pain relief” 4–6.5 V, 130 Hz, and 450 micro-s Deepest contact used as cathode and most superficial anode 5 infections 4 seizures 2 lead damage Ben-Haim 2018 [ 40 ] DBS Target: PAG/PVG, VPM 4 TNP/“atypical facial pain” 2 PSP (facial pain) 1 Post-trauma [ 7 ] 55.1 [34–71] 4:3 [13–50] 9.0 ± 1.3 2.6 ± 1.5 At 12 m, 70% 6/7 had ≥50% improvement PAG/PVG 1–5 V; 30–60 Hz; 90–200 micro-s VPM 1–5 V; 30–70 Hz; 90–180 micro-s 1 transient diplopia Kashanian 2020 [ 41 ] DBS Target: VPM [ 3 ], VPM + PVG [ 4 ] 2 post-traumatic facial pain 2 PSP (facial pain) 2 PHP (facial pain) 1 atypical facial pain) [ 7 ] (Initially 9 but 8 had IPG implantation and only 7 had sufficient follow-up and were included for analysis) 57.0 ± 15.5 [39–81] 5:4 40.3 9.4 (n = 7) 6.1 (n = 7) 55% for post-traumatic facial pain; 45% for PSP; 15% for PHP; 0% for atypical facial pain 2 of 7 (29%) met criteria for responders (≥50% decrease in pain scores) PVG 0.0–4.8 V; 25–105 Hz; 150–330 micro-s VPM 2.4–4 V; 90–160 Hz; 60–330 micro-s 3/8 had implant-related complications requiring removal (2 infections and 1 surgical pain-related) Abdallat 2021 [ 91 ] DBS Target: CM-Pf + VPL (or VPM) 11 Post-stroke/central 8 CRPS 6 Facial pain 4 CPSP 4 PHP 4 SCI 2 PSPS 1 PLP (33/40 had IPG implantation) 18 had follow-up > 4 yrs (10 CM-Pf, 1 CM-Pf + VPL, 7 VPL/VPM) 53.5 ± 14.3 20:20 62.8 [3–180] 7.1 ± 1.6 at baseline 3.3 ± 2.1 for those available for final follow-up 53.8% 8/18 had ≥50% max VAS score improvement (11/18 had ≥30% improvement) 10/18 had ≥50% av. VAS score improvement (16/18 had ≥30% improvement) At final follow-up, CM–Pf: 2.5 ± 0.8 V, 131 ± 4.2 Hz, 210 ± 0 micro-s; VPL/VPM: 2.1 ± 1.0 V, 129 ± 5.5 Hz, 207 ± 45 micro-s 11/33 hardware complications, including 5 explantations due to infection Note: no difference in CM-Pf vs VPM/VPM stimulation Best results achieved in facial pain, poststroke/central pain (except thalamic pain), or brachial plexus injury; while patients with thalamic lesions had the least benefit Mandat 2023 [ 42 ] DBS Target: PAG/PVG 5 PSP (facial pain) 2 craniofacial injury [ 7 ] 2 had MCS before; 3 had thalamic DBS before 43.7 ± 12.1 [28–62] 4:3 24 8.6 ± 0.8 At 24 mon, 4.7 ± 1.8 At 24 mon, 45 ± 22% 5/7 had 50% improvement Start with (monopolar) 50 Hz, 1 V, 60 micro-s and gradually increased to 5 V depending on response Transient adverse effect related to stimulation: diplopia, paresthesia Simpson 2003 [ 46 ] SCS 15 CRPS 5 Amputation 4 PSPS 3 Raynaud's 3 AN 1 Other facial pain 1 CPSP 1 SCI 1 Others [ 41 ] Med 48 [26–76] Median 4 yrs 7 mon [5mon-11yr] NA NA NA “Significant” pain relief in 51% but not in facial pain cohort Epidural paddle lead; location varies from C1 to C7/T1 level 80 Hz; pulse width 200 or 210 micro-sec; amplitude slightly above the perception threshold 37 re-operations, mainly for receiver exploration/replacement [ 16 ] and electrode replacement for improving topography [ 6 ] 6 lead fractures, 3 electrode dislodgement; 5 stimulation too postural; 2 infections; 1 awaiting diagnosis Tomycz 2011 [ 155 ] SCS 7 AN 4 TNP 2 PHP 1 PSP (facial) 2 ON [ 16 ] (only 16/25 patients with implantation had follow-up) Med 51.6 [17–78] 7:9 53.4 [2–120] 9.6 2/16 bilateral pain 4.8 50% 12 had “significantly improved” quality of life 50% reported reduced oral medication use Paddle lead in epidural CCJ (after successful trial) with SSEP guidance (parameters NA) 25% (4/16) removed due to loss of effectiveness [ 3 ] and infection [ 1 ] 1 reported uncomfortable paresthesia secondary to connecting wire insulation breakdown Chivukula 2014 b [ 156 ] SCS 10 AN 7 ON 4 TNP 4 PHP [ 25 ] Also include other 75 cervical SCS patients in paper 46.4 ± 12.0 in all patients 35:65 in all patients 3.9 yrs [1–12 yrs] AN: 8.1 ± 0.7 ON: 8.1 ± 0.7 TNP: 8.0 ± 0.8 PHP: 8.8 ± 0.8 AN: 3.6 ± 0.8 ON: 4.0 ± 0.8 TNP: 3.3 ± 0.5 PHP: 3.8 ± 1.3 AN: 55.1 ON: 51 TNP: 59 PHP: 61 Average of >50% pain relief in all patient groups Paddle lead in epidural CMJ (after successful trial) (parameters NA) 5 lead migration and 4 other revisions 2 infections Velásquez 2018 [ 44 ] SCS 12 TNP 53.8 [42–68] 5:7 4.4 yrs [0.3–21.1 yrs] Median 7 All unilateral pain Median 3 57.1% reduction in median NRS Average coverage in pain zone 72% Long term failure rate 25% Paddle lead in epidural CMJ (after successful trial) Tonic stimulation (parameters NA) 1 infection 7 underwent further procedures with 19 system revisions Basha 2023 [ 157 ] SCS 3 TNP 56,46,35 0:3 24.9 NA NA NA 1 with partial satisfactory relief at 13.9 mon Upper cervical SCS (most superior electrode above C1 lamina) (parameters NA) 2 with therapeutic failure after 4.7 mon and 34.2 mon Edelbach 2023 [ 158 ] SCS 2 TN 76,29 0:2 4 weeks and 6 months 10/10 for both cases 6/10 and 4/10 See left 300 Hz; 170 ms; 0.5–0.8 mA in one patient, 1.8–2.2 mA in the other Percutaneous upper cervical SCS (1 case C1–C2; 1 case C2–C4) None reported Malik 2024 [ 159 ] SCS 2 Facial CRPS 73,64 2:0 6 1 improved from 5/10 to 2/10; the other improved from 7/10 to 2/10 Cervical SCS (advanced to superior aspect of C2 vertebral body) Burst stimulation (intraburst 500 Hz, overall 40 Hz, 1 ms pulse width) None reported Jiang 2025 [ 47 ] SCS 62 pregabalin + SCS 59 pregabalin alone (121 PHP facial pain patients) 32:30 33:26 65.9 ± 8.1 vs 65.±8.7 12 weeks 7.9 ± 1.7 vs 7.6 ± 2.0 2.5 ± 1.5 vs 4.5 ± 2.5 68% vs 41% 95% vs 83% NA 1 infection; 2 dizziness; 1 hematoma Hameroff 2013 [ 31 ] TUS Target: posterior frontal cortex contralateral to side of pain 31 patients (2 with facial pain) Unclear etiologies 52.8 [29–83] 12:19 Assessed in the same session After 40 min, there is some improvement in pain score NRS of placebo was 6.9 ± 0.6 vs TUS group of 6.2 ± 0.8. Not statistically significant ( p = 0.07) Global Affect score was better (placebo, 56.8 ± 6.1; TUS, 58.6 ± 5.5; p = 0.04) (double-blinded) NA 8 MHz subthermal TUS (single session) vs placebo 1 had transient headache Open in a new tab % Likely Overlaps with study [ 160 ]. These papers have the same first/senior authors and may have overlap of data: [ [23] , [24] , [25] , 27 , 30 , 128 ]. a There is some overlap of this study with Rasche 2016 [ 143 ]. b Overlaps with study by Tomycz et al., 2011. Fig. 2. Open in a new tab Targets and modalities for neuromodulation to treat facial pain in the central nervous system. Created with Biorender.com . ACC, anterior cingulate cortex; CM, centromedian nucleus of thalamus; DBS, deep brain stimulation; LIFU, low-intensity focused ultrasound; M1, primary motor cortex; MCS, motor cortex stimulation; PAG, periaqueductal grey; Pf, parafascicularis nucleus of thalamus; rTMS, repetitive transcranial magnetic stimulation; tDCS, transcranial direct current stimulation; VPM, ventral posterior medial nucleus; VPL, ventral posterior lateral nucleus. Non-invasive (incisionless) techniques Transcranial direct current stimulation (tDCS) tDCS is a non-invasive neuromodulation technique where two electrodes are typically placed on the scalp. During stimulation, current flows between the electrodes, leading to an enhancing or inhibitory effect on the excitability of the underlying cortex [ 15 ]. In the five articles included that utilized tDCS, most targeted the primary motor cortex (M1), except one study targeting the dorsolateral prefrontal cortex (dlPFC). Treatment duration ranged from five consecutive days to three weeks). All published studies reported an improvement in pain score (NRS or VAS). In those with outcome reported between two to four weeks, sham-controlled, M1-targeting studies demonstrated improvements of 18%, 19%, 28%; whereas the single study targeting dlPFC reported a 22% improvement [ [16] , [17] , [18] , [19] ]. One uncontrolled, unblinded study with one week follow-up reported 79% and 83% improvement after treatments targeting the somatosensory cortex and M1, respectively [ 20 ]. Only one study reported adverse effects (fatigue and headache) but these occurred in the sham group as well. Repetitive transcranial magnetic stimulation (rTMS) rTMS is another non-invasive technique that modulates the cortical activity by applying magnetic pulses through the skull using a coil [ 21 ]. It has been shown to be effective in improving motor and cognitive function in a number of different conditions, such as depression and neuropathic pain [ 21 , 22 ]. Among the 13 studies included, all targeted the M1 region. While some targeted the cortical representation of the painful area according to the motor homunculus [ [23] , [24] , [25] , [26] ], some simply targeted the hand area [ 24 , 27 , 28 ]. One study demonstrated that it was actually more effective to target the hand area than the face area to treat the facial pain [ 24 ]. Follow-up varied from immediately after treatment to 180 days post-treatment. Apart from two negative studies that showed no improvement for facial pain [ 4 , 23 ], in studies with follow-up within one month, improvement in pain score ranges from 11 to 44% [ 27 , 28 ]. One study with follow-up at 6 weeks showed 55.0% improvement in VAS in “responders” (28 out of 48) but 2.3% in “non-responders” [ 29 ]. Another study with follow-up at 180 days demonstrated 90% improvement in paroxysmal pain and 62% improvement in permanent pain [ 30 ]. Most studies used either 10 or 20 Hz, with one comparative study showing a 20 Hz frequency being superior to 10 Hz [ 26 ]. In addition to tDCS and rTMS, we included a single study ( Table 1 ) using transcranial (subthermal) low intensity focused ultrasound (LIFU) where a single session therapy was applied and was supposed to modulate the brain area without permanent lesioning the brain structure [ 31 ]. Invasive techniques Motor cortex stimulation (MCS) As with most tDCS and rTMS studies, MCS targets the M1 cortex. In most cases, a paddle electrode is implanted over the region of the motor cortex and this is connected to a pulse generator. Electrode applies direct, focal electrical stimulation over the region at a level below the threshold that would stimulate motor responses. While some use a trial stimulation with the connection of the grid externalized [ 32 ], some found success in using rTMS as a trial to select candidates for permanent MCS implantation [ 33 ]. The latter can be performed either in a subdural or an epidural fashion, with different complication profiles as listed in Table 1 . Among the 18 articles included, follow-up ranged from seven months up to 170 months post-treatment. Pain scores improved from 11.1 to 66.8%. While all studies reported a heterogeneous mixture of patients, one study with mostly facial pain patients (29 out of 46) reported a 57.3% improvement in pain score [ 32 ]. Reflecting the invasive nature of MCS, there is a significant risk of infection and seizure associated with the treatment. Deep brain stimulation (DBS) DBS involves the implantation of electrodes deep into key parts of the brain to modulate the function of the dysfunctional neural network. While its main clinical use is in movement disorders such as Parkinson's disease and essential tremor, its use extends to other more novel neuropsychiatric diseases such as depression, obsessive-compulsive disorder, drug addiction, Tourette's syndrome [ [34] , [35] , [36] , [37] , [38] ]. Unlike tDCS, rTMS, and MCS, DBS is capable of delivering direct, focal stimulation to deep nuclei of the brain with high precision that other techniques could not achieve. Among the 12 DBS studies, a range of different targets have been employed ( Fig. 2 ). The commonest target used was the main sensory nuclei of thalamus, i.e. , ventral posterior lateral nucleus (VPL) and VPM of thalamus. Other targets also included the periaquectal grey/periventricular grey (PAG/PVG), CM-Pf, ACC, posterior hypothalamus, and internal capsule. Most studies had at least 18 months of follow-up. Among studies that only include facial pain pathologies, posterior hypothalamus DBS improved the pain in all five patients with TN secondary to multiple sclerosis but not those with trigeminal neuropathic pain [ 39 ]. PAG and/or CM-Pf DBS alleviates anesthesia dolorosa pain up to 73% (better in combination). Another study showed that PAG/PVG and VPM DBS can improve pain up to 70% at 12 months [ 40 ]. Longer term studies with over 40 month follow-up demonstrated over 40% improvement in post-traumatic and post-stroke facial pain but it appears to be less effective (up to 15% improvement) in post-herpetic and atypical neuropathic facial pain [ 41 , 42 ]. The commonest reported serious adverse effect is infection ( Table 1 ) [ 43 ]. Spinal cord stimulation (SCS) Nucleus caudalis (NC), located in the dorsolateral part of the cervicomedullary junction, is one of the three sub-nuclei in the spinal trigeminal nucleus and plays an important part in facial nociception [ 44 ]. NC dorsal root entry zone nucleotomy/tractotomy has been shown to be successful in treating craniofacial pain. External stimulation using SCS has been recommended by professional bodies for treatment of facial pain as well [ 45 ]. The 8 studies included mostly utilized upper cervical stimulation and most reported positive outcome, with follow-up ranging from four weeks to more than four years, and 40–68% improvement in pain score. However, cervical SCS insertion does come with significant complication rate, where one earlier study (including other indications as well as facial pain) reported 37 re-operations among 41 patients [ 46 ]. Yet, a latter study cited only 4 complications (one infection; two dizziness; one hematoma) among 62 patients [ 47 ]. Discussion This article reviewed the key literature using modulation of the CNS as treatment of refractory facial pain. While there is an armamentarium of different techniques, there are limitations in each of them. For example, non-invasive techniques such as tDCS and rTMS may only offer response of limited nature by targeting superficial targets, while eliminating the need for an open surgery or permanent implant. On the other hand, DBS offers a window to stimulate deep structures within the maladaptive neural network with accompanying surgical risks. Interestingly, in an industry-sponsored analysis of two large DBS for pain trials of 246 patients (not focusing on facial pain) published in 2001, DBS was not found to be effective in long-term pain relief [ 48 ]. The targets included PAG/PVG, internal capsule and VPM/VPL. The majority of patients in this study had lumbar spinal-related pain and it was not clear how many had facial pain as the main issue. However, due to the heterogeneity of the patient characteristics and targets, it was difficult to conclude DBS is not effective for chronic pain treatments. Indeed, several trials since have suggested otherwise as indicated in this review. Targeted neurostimulation While facial pain is initially modulated via the somatosensory pathway, chronic neuroplastic changes involving the interactions of neurotransmitters such as glutamate, substance P and GABA play a critical role in the persistence of the disease. This leads to both peripheral and central sensitization [ 10 ]. The aim of some of the treatments described here is to reverse the maladaptive changes in the CNS [ 9 ]. Furthermore, structures such as the ACC, PAG, dorsolateral prefrontal cortex, are both DBS targets associated with facial pain improvement and areas associated with the central sensitization of pain [ 49 ]. Indeed, they were shown to have decreased grey matter volume in TN patients [ 5 ]. This demonstrates the critical importance of CNS structures and functions in the pathophysiology of chronic pain, consolidating its potential as a treatment target. According to one review, cortical pain regions can be divided into three levels in a matrix [ 49 ]. Primary cortical pain matrix (primary somatosensory and secondary somatosensory cortex, parietal operculum, and posterior insula) is involved in pain perception and localization; whereas secondary cortical pain matrix (ACC, anterior insula, amygdala, hippocampus) is involved in affective and emotional experience. Third cortical pain matrix (frontal cortex e.g., prefrontal cortex, medial and posterior cingulate) is involved in cognitive and behavioral response [ 49 , 50 ]. This classification may be helpful in targeting different components of the chronic pain syndrome. As DBS involves precise, targeted stimulation, studies have offered a unique window to scrutinize the different neurocircuits. As discussed in Introduction section, the studied targets are all important nodes in the relevant pain circuitry. While each structure has multiple functions and embeds in a complex interwoven network, we can simplify their main functions in simple terms ( Table 2 ). Further studies would help to delineate the different components of pain improved by DBS at each of these targets, beyond the unidimensional pain scale. In addition to DBS, MCS also provides targeted stimulation of key structures involved in pain modulation. Table 2. DBS targets and simplified role in the pain circuit [ 11 , 39 , 161 ]. ACC, anterior cingulate cortex; CM, centromedian nucleus of thalamus; DBS, deep brain stimulation; MS, multiple sclerosis; PAG, periaquectal grey; Pf, parafascicularis nucleus of thalamus; TN, trigeminal neuralgia; VPM, ventral posterior medial nucleus; VPL, ventral posterior medial nucleus. DBS target Main function in pain mediation VPM/VPL Sensory discrimination PAG Key in descending pain modulation and regulating affective response CM-Pf Mediates sensorimotor aspect of pain and orchestrates affective and motivational aspect of pain Also regulates arousal ACC Processing of affective and motivational aspects of pain Posterior hypothalamus Control of responses from autonomic nervous system Open in a new tab Motor cortex neuromodulation The mechanism of action of tDCS and rTMS targeting M1 and MCS is currently still under investigation. It appears targeting both the cortical representation of the painful area (according to the motor homunculus) or simply the hand area [ [23] , [24] , [25] , [26] , [27] , [28] ] may both yield analgesic effect. There are a number of plausible explanations. Some suggested MCS triggers rapid, phasic activation of lateral thalamus, which leads to a cascade of events of longer time-course in medial thalamus, ACC, orbitofrontal cortices, and PAG [ 51 ]. This modulates the emotional appraisal of pain and causes descending inhibition towards spinal cord. Another possibility may be the recruitment of GABAergic interneurons from motor cortex, which project to a range of targets such as somatosensory cortex and striatum [ 52 , 53 ]. Stimulation of the motor cortical region may also help to restore altered thalamocortical rhythm which underpins the pathophysiology of chronic neuropathic pain [ 54 ]. Furthermore, recent fMRI studies revealed there are non-motor regions within the motor cortex that account for the analgesic effect of rTMS and MCS [ 55 ]. Identifying these regions would potentially allow targeted individualized rTMS and MCS using navigation system [ 56 ]. Radiological advances Not only are advanced imaging techniques increasingly helpful in explaining underlying mechanism of action of the interventions, but new imaging findings would also potentially help to identify new treatment targets for neuromodulation. While our literature search confirms neuromodulation of several targets within the trigeminal nociceptive system and pain modulatory pathways shows promise in the alleviation of facial pain [ [57] , [58] , [59] ], it will be helpful to find new targets or refine our targeting to improve treatment efficacy. Radiological changes associated with facial pain, particularly for TN, have been widely studied [ [60] , [61] , [62] , [63] , [64] , [65] ]. In addition to neurovascular conflicts and changes to the microstructure of the trigeminal nerve [ 59 ], different areas of the CNS exhibit changes. For example, these include hippocampus [ 64 , 66 , 67 ], thalamic nuclei [ 68 ], basal ganglia [ 62 , 65 , 68 , 69 ], amygdala [ 70 ], cortical regions including the insula, primary motor/sensory cortex, ACC, and cerebellum [ 62 , 65 , [71] , [72] , [73] ]. More recently, resting-state fMRI (rs-fMRI) has been increasingly used for this purpose, revealing perturbations in the default mode network, salience network, and sensorimotor network [ [74] , [75] , [76] , [77] ]. Interestingly, compared to healthy controls, the changes also appeared to lateralize to either the right or left side, depending on the area of interest [ 73 , 78 ]. The use of diffusion tensor imaging (DTI) also identified structural changes of both the trigeminal nerve itself and the subregions of thalamus associated with TN [ 57 , 59 ]. Ongoing preclinical and clinical trials While it is challenging to conduct animal studies of chronic facial pain, several relevant basic science studies cast light onto the etiology and potential treatments, despite the differences in anatomy and physiology to humans. One rodent study found MCS led to transient inhibition of responses of spinal cord dorsal horn neurons to higher intensity mechanical stimuli without affecting their response to innocuous stimulus, supporting the selective therapeutic effect [ 79 ]. Likewise, optogenetic stimulation of motor cortex and tDCS alleviated pain behaviors and biochemical abnormalities in a rodent model of trigeminal neuropathic pain with infraorbital nerve constriction [ 80 , 81 ]. Furthermore, focused ultrasound stimulation of deep thalamic nuclei of adult macaque monkeys was found to suppress nociceptive heat stimulation-induced responses [ 82 ]. A number of ongoing clinical trials are also exploring the efficacy of chronic pain treatment using the different treatment modalities described here. Including those with active or unknown status (some of these may have been completed but not updated), there is one tDCS studies and four rTMS studies in the treatment of facial pain on the ClinicalTrials.gov registry [ [83] , [84] , [85] , [86] , [87] ]. Despite the long history in the use of MCS, there is one industry-sponsored trial studying MCS for chronic neuropathic pain [ 88 ]. There are two DBS trials [ 89 , 90 ], with one using thalamic stimulation and the other one without a specified target. Adverse effects Depending on the invasiveness of the intervention, the long-term effect of adverse events also varies. For tDCS and rTMS, most studies reported no side-effects and those that were listed are mostly transient or minor side-effects, such as fatigue and headache. However, most of the studies have follow-up less than 2 months, so the overall side-effect profile and therapeutic effect is less clear. Conversely, more invasive procedures such as MCS and DBS have longer follow-up periods but more serious adverse effects such as seizures, hematoma, stroke, and infections were reported, which can lead to serious morbidity and may necessitate explanation of device. Interestingly, the rate of reported complications is highly variable. One study reported one third of 33 hardware experienced complications after DBS [ 91 ]; while another study of 38 patients only had three complications [ 92 ]. Both studies had similar follow-up times (average 45 vs 63 months) This may be due to different surgical techniques or under-reporting in some cases. With SCS, an earlier study in 2003 reported 37 re-operations among 41 patients [ 46 ] but latter studies had much lower rates of adverse effects [ 47 ], which may be due to better surgical technique and hardware development. Given the different adverse effects, it is important for clinicians to counsel patients appropriately regarding the risk and benefit profile of each treatment modality. Limitations There are several limitations associated with this review. First, there are overlapping features between facial pain and headache syndromes. In the current review, we excluded studies that focus on the latter so there is potentially relevant information that was missed. However, given headache treatments and classification are rather distinct from facial pain [ 93 ], we attempted to keep our review more focused on facial pain itself. Likewise, we have not included studies focusing on neuropathic pain in other areas of the body outside the face. Hence, this may not capture all of the pain literature involved. For similar reasons, we excluded studies with a predominant focus on post-stroke pain, unless it is specifically involving the facial distribution. In the current review, we have excluded studies that performed lesioning with techniques such as open radio frequency ablation, stereotactic radiosurgery (SRS) and MRI-guided focused ultrasound (MRgFUS) [ [94] , [95] , [96] , [97] , [98] , [99] , [100] , [101] , [102] , [103] , [104] , [105] ]. This may have excluded discussion of potential neuromodulatory targets. This is also important since lesioning techniques and neuromodulatory techniques are not mutually exclusive [ 106 ]. However, lesioning often has a more limited therapeutic window compared to the techniques described here due to the inherent irreversible nature of the treatment and they often have other technical challenges [ 107 , 108 ]. Furthermore, the number of studies involving incisionless modalities are currently limited and restricted to more specialized centers. This may make their results less generalizable to a general neurosurgical center. The authors have also excluded single case reports due to the relative lack of validity. The intention is to keep the review based on higher level of evidence and restricted to those performed by more experienced centers. Likewise, we did not include smaller studies for MCS that predominantly consist of facial pain patients such as [ 109 , 110 ] but we believe given the long history and widespread use of MCS in facial pain and other forms of neuropathic pain, it helps to focus down to higher quality studies by restricting to studies with larger sample size and those with more experience in the treatment modality. Yet, almost all studies included here are positive studies, which raises high suspicion of publication bias. In addition, the heterogeneity of the research studies also precludes the feasibility of a formal meta-analysis and limits the overall conclusions. For example, the variable follow-up periods across studies (even within the same treatment modality) led to difficulty in comparison. Also, short follow-up periods among tDCS studies also limits the conclusion for its efficacy. Moreover, the definition of “responders” varies widely. For example, some used the threshold of 30% improvement in NRS pain score while some used 50%; others may use the Barrow Neurological Institute pain scale instead. This added further challenges in the comparison of studies. Often the reported cases contain a mixed cohort of non-facial pain and facial pain cases. Treatment outcome was often not reported for individual patients and therefore, we could only analyze the collective results of those with facial pain and those with other distributions of pain. Therefore, it is difficult for us to draw firm conclusions about the efficacy in the treatment of facial pain alone. Methods of measuring outcomes also vary between studies. While most report pain score (NRS/VAS), not all of them do that. For example, some reported temperature sensation threshold [ 17 ] instead. Some but not all studies also reported other quality-of-life measures, such as depression or anxiety scores [ 19 ]. While these measures may not be a direct measurement of the pain sensation, they may be important for individual patients, depending on the underlying diagnosis and comorbidity. Specifically within DBS studies, targeting areas such as the CM-Pf or VP nuclei of the thalami require indirect targeting with the coordinates based on atlases [ 42 , 91 ]. Therefore, there may be error due to individual anatomical differences and the wide range of surgeons’ techniques [ 40 , 91 , [111] , [112] , [113] , [114] ]. Future directions A reporting framework for further studies standardizing the stimulation parameters and outcome measures (pain scale, psychiatric inventory, quality of life inventory, follow-up period) would be helpful to facilitate analysis of future research. For example, with the advances in transcranial ultrasound, a new consensus guideline for reporting was recently proposed [ 115 ]. Definition of facial pain such as TN, trigeminal neuropathic pain and atypical facial pain should also follow internationally agreed nomenclature [ 93 ]. Novel techniques such as LIFU appeared to have the ability to penetrate into deep areas of the brain in an incisionless fashion without inducing radiation [ [116] , [117] , [118] ]. One recent study appeared to succeed in doing so with twenty patients who suffered from chronic pain from a mixture of diagnoses by targeting the rostral ACC with focused ultrasound [ 119 ]. Interestingly, previous studies focused on a more posterior ACC target than this study [ 120 ]. It is possible LIFU may serve as a non-invasive way of providing “test” stimulation prior to permanent implantation of DBS. There are also healthy subject studies that received sonication of the anterior thalamus [ 121 ], which was found to raise the pain threshold. Future studies should aim to elucidate a decision-making algorithm for different subtypes of patients in terms of modality and CNS target selection. Advances of technologies in biomarker measurements also provide potential for closed-loop neuromodulation. Electrophysiological changes, such as local field potential of ACC and thalamus [ [122] , [123] , [124] ], advanced imaging findings [ 59 ], and neurochemical measurements [ 125 ] may potentially be used as biomarkers. This can facilitate selection of patients, stimulation parameters, and treatment modalities. Conclusion The use of both non-invasive and invasive neuromodulation of the CNS to treat facial pain was reviewed in this article. In particular, the techniques of tDCS, rTMS, MCS, DBS, SCS, and focused ultrasound all showed promising results, despite different adverse effect profiles. The use of incisionless techniques provides the advantage of minimizing procedural risks while modulating critical brain structures. However, the heterogeneity of study designs poses challenges in direct comparison of the techniques and confirming the optimal stimulation parameters. Further studies with standardized framework would help to provide evidenced-based guidelines for clinical use. Author contribution Jason Yuen : Conceptualization, Data curation, Methodology, Formal analysis, Writing - original draft, Writing - review & editing. Aaron Loh : Data curation, Writing - review & editing. Ghazal Darmani : Methodology, Data curation, Writing - review & editing. Can Sarica : Writing - review & editing. Nikunj Patel : Methodology, Writing - review & editing. Andres Lozano : Resources, Supervision, Writing - review & editing. Mojgan Hodaie : Conceptualization, Methodology, Resources, Supervision, Writing - review & editing. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgments None. References 1. Murray H., Locker D., Mock D., Tenenbaum H.C. Pain and the quality of life in patients referred to a craniofacial pain unit. J Orofac Pain. 1996;10(4):316–323. [ PubMed ] [ Google Scholar ] 2. Breckons M., Shen J., Bunga J., Vale L., Durham J. DEEP study: indirect and out-of-pocket costs of persistent orofacial pain. J Dent Res. 2018;97(11):1200–1206. doi: 10.1177/0022034518773310. [ DOI ] [ PubMed ] [ Google Scholar ] 3. Porporatti A.L., Schroder A.G.D., Lebel A., Moreau N., Guillouet C., Stechman-Neto J., et al. Prevalence of orofacial and head pain: an umbrella review of systematic reviews. J Oral Facial Pain Headache. 2024;38(3):1–14. doi: 10.22514/jofph.2024.022. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 4. Headache Classification Committee of the International Headache Society (IHS) The international classification of headache disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211. doi: 10.1177/0333102417738202. [ DOI ] [ PubMed ] [ Google Scholar ] 5. Ashina S., Robertson C.E., Srikiatkhachorn A., Di Stefano G., Donnet A., Hodaie M., et al. Trigeminal neuralgia. Nat Rev Dis Primers. 2024;10(1):39. doi: 10.1038/s41572-024-00523-z. [ DOI ] [ PubMed ] [ Google Scholar ] 6. Weiss A.L., Ehrhardt K.P., Tolba R. Atypical facial pain: a comprehensive, evidence-based review. Curr Pain Headache Rep. 2017;21(2):8. doi: 10.1007/s11916-017-0609-9. [ DOI ] [ PubMed ] [ Google Scholar ] 7. Petersen E., Suen J.Y. Springer International Publishing : Imprint: Springer; Cham: 2018. Diagnosis and management of head and face pain : a practical approach. [ Google Scholar ] 8. Sarica C., Iorio-Morin C., Aguirre-Padilla D.H., Paff M., Villeneuve S.A., Vetkas A., et al. Clinical outcomes and complications of peripheral nerve field stimulation in the management of refractory trigeminal pain: a systematic review and meta-analysis. J Neurosurg. 2022;137(5):1387–1395. doi: 10.3171/2021.12.JNS212869. [ DOI ] [ PubMed ] [ Google Scholar ] 9. Jayathilake N.J., Phan T.T., Kim J., Lee K.P., Park J.M. Modulating neuroplasticity for chronic pain relief: noninvasive neuromodulation as a promising approach. Exp Mol Med. 2025;57(3):501–514. doi: 10.1038/s12276-025-01409-0. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 10. Chichorro J.G., Porreca F., Sessle B. Mechanisms of craniofacial pain. Cephalalgia. 2017;37(7):613–626. doi: 10.1177/0333102417704187. [ DOI ] [ PubMed ] [ Google Scholar ] 11. Chung M., Huh R. Neuromodulation for trigeminal neuralgia. J Korean Neurosurg Soc. 2022;65(5):640–651. doi: 10.3340/jkns.2022.0004. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 12. Colloca L., Ludman T., Bouhassira D., Baron R., Dickenson A.H., Yarnitsky D., et al. Neuropathic pain. Nat Rev Dis Primers. 2017;3 doi: 10.1038/nrdp.2017.2. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 13. Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Rev Esp Cardiol. 2021;74(9):790–799. doi: 10.1016/j.rec.2021.07.010. [ DOI ] [ PubMed ] [ Google Scholar ] 14. Yuen J.W.H. 2025. OSF registration - “central neuromodulation for facial pain”. [ Google Scholar ] 15. Thair H., Holloway A.L., Newport R., Smith A.D. Transcranial direct current stimulation (tDCS): a beginner's guide for design and implementation. Front Neurosci. 2017;11:641. doi: 10.3389/fnins.2017.00641. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 16. Antal A., Terney D., Kuhnl S., Paulus W. Anodal transcranial direct current stimulation of the motor cortex ameliorates chronic pain and reduces. Short Intracortical Inhibition. 2010;(5):890–903. doi: 10.1016/j.jpainsymman.2009.09.023. [ DOI ] [ PubMed ] [ Google Scholar ] 17. Bae S.H., Kim G.D., Kim K.Y. Analgesic effect of transcranial direct current stimulation on central post-stroke pain. Tohoku J Exp Med. 2014;234(3):189–195. doi: 10.1620/tjem.234.189. [ DOI ] [ PubMed ] [ Google Scholar ] 18. Hagenacker T., Bude V., Naegel S., Holle D., Katsarava Z., Diener H.C., et al. Patient-conducted anodal transcranial direct current stimulation of the motor cortex alleviates pain in trigeminal neuralgia. J Headache Pain. 2014;15(1):78. doi: 10.1186/1129-2377-15-78. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 19. Fricová J., Englerová K., Nedvídek J., Rokyta R. The treatment of orofacial pain by using transcranial direct current stimulation. Physiol Res. 2019;68(Suppl 3):S367. doi: 10.33549/physiolres.934361. s72. [ DOI ] [ PubMed ] [ Google Scholar ] 20. Babakhani B., Tabatabaei N.H., Elisevich K., Sadeghbeigi N., Barzegar M., Mobarakeh N.M., et al. A preliminary study of the efficacy of transcranial direct current stimulation in trigeminal neuralgia. Front Hum Neurosci. 2022;16 doi: 10.3389/fnhum.2022.848347. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 21. Yang S., Chang M.C. Effect of repetitive transcranial magnetic stimulation on pain management: a systematic narrative review. Front Neurol. 2020;11:114. doi: 10.3389/fneur.2020.00114. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 22. Somani A., Kar S.K. Efficacy of repetitive transcranial magnetic stimulation in treatment-resistant depression: the evidence thus far. Gen Psychiatry. 2019;32(4) doi: 10.1136/gpsych-2019-100074. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 23. Lefaucheur J.P., Drouot X., Nguyen J.P. Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex. Neurophysiol Clin. 2001;31(4):247–252. doi: 10.1016/s0987-7053(01)00260-x. [ DOI ] [ PubMed ] [ Google Scholar ] 24. Lefaucheur J.P., Hatem S., Nineb A., Ménard-Lefaucheur I., Wendling S., Keravel Y., et al. Somatotopic organization of the analgesic effects of motor cortex rTMS in neuropathic pain. Neurology. 2006;67(11):1998–2004. doi: 10.1212/01.wnl.0000247138.85330.88. [ DOI ] [ PubMed ] [ Google Scholar ] 25. Hodaj H., Payen J.F., Hodaj E., Dumolard A., Maindet C., Cracowski J.L., et al. Long-term treatment of chronic orofacial, pudendal, and central neuropathic limb pain with repetitive transcranial magnetic stimulation of the motor cortex. Clin Neurophysiol. 2020;131(7):1423–1432. doi: 10.1016/j.clinph.2020.03.022. [ DOI ] [ PubMed ] [ Google Scholar ] 26. Säisänen L., Huttunen J., Hyppönen J., Nissen M., Kotiranta U., Mervaala E., et al. Efficacy and tolerability in patients with chronic facial pain of two consecutive treatment periods of rTMS applied over the facial motor cortex, using protocols differing in stimulation frequency, duration, and train pattern. Neurophysiol Clin. 2022;52(2):95–108. doi: 10.1016/j.neucli.2022.03.001. [ DOI ] [ PubMed ] [ Google Scholar ] 27. Lefaucheur J.P., Drouot X., Menard-Lefaucheur I., Zerah F., Bendib B., Cesaro P., et al. Neurogenic pain relief by repetitive transcranial magnetic cortical stimulation depends on the origin and the site of pain. J Neurol Neurosurg Psychiatry. 2004;75(4):612–616. doi: 10.1136/jnnp.2003.022236. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 28. Khedr E.M., Kotb H., Kamel N.F., Ahmed M.A., Sadek R., Rothwell J.C. Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. J Neurol Neurosurg Psychiatry. 2005;76(6):833–838. doi: 10.1136/jnnp.2004.055806. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 29. Lawson McLean A., Frank S., Zafar N., Waschke A., Kalff R., Reichart R. Time course of the response to navigated repetitive transcranial magnetic stimulation at 10 Hz in chronic neuropathic pain. Neurol Res. 2018;40(7):564–572. doi: 10.1080/01616412.2018.1453636. [ DOI ] [ PubMed ] [ Google Scholar ] 30. Hodaj H., Alibeu J.P., Payen J.F., Lefaucheur J.P. Treatment of chronic facial pain including cluster headache by repetitive transcranial magnetic stimulation of the motor cortex with maintenance sessions: a naturalistic study. Brain Stimul. 2015;8(4):801–807. doi: 10.1016/j.brs.2015.01.416. [ DOI ] [ PubMed ] [ Google Scholar ] 31. Hameroff S., Trakas M., Duffield C., Annabi E., Gerace M.B., Boyle P., et al. Transcranial ultrasound (TUS) effects on mental states: a pilot study. Brain Stimul. 2013;6(3):409–415. doi: 10.1016/j.brs.2012.05.002. [ DOI ] [ PubMed ] [ Google Scholar ] 32. Yuen J., Klassen B.T., Sandroni P., Huston J., Grewal S.S., Wharen R.E., Jr., et al. Implantable subdural cortical stimulation for chronic intractable pain treatment-the Mayo experience and review of literature. Neuromodulation. 2024;27(1):200–208. doi: 10.1016/j.neurom.2023.01.013. [ DOI ] [ PubMed ] [ Google Scholar ] 33. Thomas J., Fauchon C., Oriol N., Vassal F., Créac'h C., Quesada C., et al. Effects of multiple transcranial magnetic stimulation sessions on pain relief in patients with chronic neuropathic pain: a French cohort study in real-world clinical practice. Eur J Pain. 2025;29(1) doi: 10.1002/ejp.4763. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 34. Yuen J., Kouzani A.Z., Berk M., Tye S.J., Rusheen A.E., Blaha C.D., et al. Deep brain stimulation for addictive disorders-where are we now? Neurotherapeutics. 2022;19(4):1193–1215. doi: 10.1007/s13311-022-01229-4. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 35. Rusheen A.E., Rojas-Cabrera J., Goyal A., Shin H., Yuen J., Jang D.P., et al. Deep brain stimulation alleviates tics in Tourette syndrome via striatal dopamine transmission. Brain. 2023;146(10):4174–4190. doi: 10.1093/brain/awad142. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 36. Harmsen I.E., Wolff Fernandes F., Krauss J.K., Lozano A.M. Where are we with deep brain stimulation? A review of scientific publications and ongoing research. Stereotact Funct Neurosurg. 2022;100(3):184–197. doi: 10.1159/000521372. [ DOI ] [ PubMed ] [ Google Scholar ] 37. Holtzheimer P.E., Husain M.M., Lisanby S.H., Taylor S.F., Whitworth L.A., McClintock S., et al. Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. Lancet Psychiatry. 2017;4(11):839–849. doi: 10.1016/S2215-0366(17)30371-1. [ DOI ] [ PubMed ] [ Google Scholar ] 38. Wu H., Hariz M., Visser-Vandewalle V., Zrinzo L., Coenen V.A., Sheth S.A., et al. Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy? Mol Psychiatr. 2021;26(1):60–65. doi: 10.1038/s41380-020-00933-x. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 39. Franzini A., Messina G., Cordella R., Marras C., Broggi G. Deep brain stimulation of the posteromedial hypothalamus: indications, long-term results, and neurophysiological considerations. Neurosurg Focus. 2010;29(2):E13. doi: 10.3171/2010.5.FOCUS1094. [ DOI ] [ PubMed ] [ Google Scholar ] 40. Ben-Haim S., Mirzadeh Z., Rosenberg W.S. Deep brain stimulation for intractable neuropathic facial pain. Neurosurg Focus. 2018;45(2) doi: 10.3171/2018.5.FOCUS18160. [ DOI ] [ PubMed ] [ Google Scholar ] 41. Kashanian A., DiCesare J.A.T., Rohatgi P., Albano L., Krahl S.E., Bari A., et al. Case series: deep brain stimulation for facial pain. Oper Neurosurg. 2020;19(5):510–517. doi: 10.1093/ons/opaa170. [ DOI ] [ PubMed ] [ Google Scholar ] 42. Mandat V., Zdunek P.R., Krolicki B., Szalecki K., Koziara H.M., Ciecierski K., et al. Periaqueductal/periventricular gray deep brain stimulation for the treatment of neuropathic facial pain. Front Neurol. 2023;14 doi: 10.3389/fneur.2023.1239092. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 43. Tabaja H., Yuen J., Tai D.B.G., Campioli C.C., Chesdachai S., DeSimone D.C., et al. Deep brain stimulator device infection: the Mayo clinic Rochester experience. Open Forum Infect Dis. 2023;10(1):ofac631. doi: 10.1093/ofid/ofac631. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 44. Velásquez C., Tambirajoo K., Franceschini P., Eldridge P.R., Farah J.O. Upper cervical spinal cord stimulation as an alternative treatment in trigeminal neuropathy. World Neurosurg. 2018;114:e641–e646. doi: 10.1016/j.wneu.2018.03.044. [ DOI ] [ PubMed ] [ Google Scholar ] 45. Deer T.R., Mekhail N., Petersen E., Krames E., Staats P., Pope J., et al. The appropriate use of neurostimulation: stimulation of the intracranial and extracranial space and head for chronic pain. Neuromodulation appropriateness consensus committee. Neuromodulation. 2014;17(6):551–570. doi: 10.1111/ner.12215. discussion 70. [ DOI ] [ PubMed ] [ Google Scholar ] 46. Simpson B.A., Bassett G., Davies K., Herbert C., Pierri M. Cervical spinal cord stimulation for pain: a report on 41 patients. Neuromodulation. 2003;6(1):20–26. doi: 10.1046/j.1525-1403.2003.03003.x. [ DOI ] [ PubMed ] [ Google Scholar ] 47. Jiang C., Xu X., Guan S., Chen L., Chen R., Cai X. Analysis of the effects of combined electrical spinal cord stimulation and pregabalin therapy in patients with herpes zoster trigeminal neuralgia. J Clin Neurosci. 2025;136 doi: 10.1016/j.jocn.2025.111224. [ DOI ] [ PubMed ] [ Google Scholar ] 48. Coffey R.J. Deep brain stimulation for chronic pain: results of two multicenter trials and a structured review. Pain Med. 2001;2(3):183–192. doi: 10.1046/j.1526-4637.2001.01029.x. [ DOI ] [ PubMed ] [ Google Scholar ] 49. Karcz M., Abd-Elsayed A., Chakravarthy K., Aman M.M., Strand N., Malinowski M.N., et al. Pathophysiology of pain and mechanisms of neuromodulation: a narrative review (A neuron project) J Pain Res. 2024;17:3757–3790. doi: 10.2147/JPR.S475351. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 50. Kucyi A., Davis K.D. The dynamic pain connectome. Trends Neurosci. 2015;38(2):86–95. doi: 10.1016/j.tins.2014.11.006. [ DOI ] [ PubMed ] [ Google Scholar ] 51. Garcia-Larrea L., Peyron R. Motor cortex stimulation for neuropathic pain: from phenomenology to mechanisms. Neuroimage. 2007;37(Suppl 1):S71–S79. doi: 10.1016/j.neuroimage.2007.05.062. [ DOI ] [ PubMed ] [ Google Scholar ] 52. Tremblay R., Lee S., Rudy B. GABAergic interneurons in the neocortex: from cellular properties to circuits. Neuron. 2016;91(2):260–292. doi: 10.1016/j.neuron.2016.06.033. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 53. Melzer S., Gil M., Koser D.E., Michael M., Huang K.W., Monyer H. Distinct corticostriatal GABAergic neurons modulate striatal output neurons and motor activity. Cell Rep. 2017;19(5):1045–1055. doi: 10.1016/j.celrep.2017.04.024. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 54. Henderson L.A., Peck C.C., Petersen E.T., Rae C.D., Youssef A.M., Reeves J.M., et al. Chronic pain: lost inhibition? J Neurosci. 2013;33(17):7574–7582. doi: 10.1523/JNEUROSCI.0174-13.2013. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 55. Gordon E.M., Chauvin R.J., Van A.N., Rajesh A., Nielsen A., Newbold D.J., et al. A somato-cognitive action network alternates with effector regions in motor cortex. Nature. 2023;617(7960):351–359. doi: 10.1038/s41586-023-05964-2. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 56. Lefaucheur J.P., Mussigmann T., Bapst B., Bardel B. Tracking non-motor regions of the motor cortex with navigated TMS for the treatment of chronic pain. Brain Stimul. 2025;18(6):1777–1778. doi: 10.1016/j.brs.2025.09.015. [ DOI ] [ PubMed ] [ Google Scholar ] 57. Li X., Zhao H., Wang M., Li L., Wang X., Ma Z., et al. Thalamic segmentation based on diffusion tensor imaging in patients with trigeminal neuralgia. Brain Res. 2024;1830 doi: 10.1016/j.brainres.2024.148832. [ DOI ] [ PubMed ] [ Google Scholar ] 58. Moisset X., Villain N., Ducreux D., Serrie A., Cunin G., Valade D., et al. Functional brain imaging of trigeminal neuralgia. Eur J Pain. 2011;15(2):124–131. doi: 10.1016/j.ejpain.2010.06.006. [ DOI ] [ PubMed ] [ Google Scholar ] 59. Watanabe M., Shrivastava R.K., Balchandani P. Advanced neuroimaging of the trigeminal nerve and the whole brain in trigeminal neuralgia: a systematic review. Pain. 2025;166(2):282–310. doi: 10.1097/j.pain.0000000000003365. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 60. DeSouza D.D., Hodaie M., Davis K.D. Abnormal trigeminal nerve microstructure and brain white matter in idiopathic trigeminal neuralgia. Pain. 2014;155(1):37–44. doi: 10.1016/j.pain.2013.08.029. [ DOI ] [ PubMed ] [ Google Scholar ] 61. Bendtsen L., Zakrzewska J.M., Heinskou T.B., Hodaie M., Leal P.R.L., Nurmikko T., et al. Advances in diagnosis, classification, pathophysiology, and management of trigeminal neuralgia. Lancet Neurol. 2020;19(9):784–796. doi: 10.1016/S1474-4422(20)30233-7. [ DOI ] [ PubMed ] [ Google Scholar ] 62. Hayes D.J., Chen D.Q., Zhong J., Lin A., Behan B., Walker M., et al. Affective circuitry alterations in patients with trigeminal neuralgia. Front Neuroanat. 2017;11:73. doi: 10.3389/fnana.2017.00073. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 63. Tohyama S., Walker M.R., Zhang J.Y., Cheng J.C., Hodaie M. Brainstem trigeminal fiber microstructural abnormalities are associated with treatment response across subtypes of trigeminal neuralgia. Pain. 2021;162(6):1790–1799. doi: 10.1097/j.pain.0000000000002164. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 64. Hanycz S.A., Noorani A., Hung P.S., Walker M.R., Zhang A.B., Latypov T.H., et al. Hippocampus diffusivity abnormalities in classical trigeminal neuralgia. Pain Rep. 2024;9(3) doi: 10.1097/PR9.0000000000001159. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 65. DeSouza D.D., Davis K.D., Hodaie M. Reversal of insular and microstructural nerve abnormalities following effective surgical treatment for trigeminal neuralgia. Pain. 2015;156(6):1112–1123. doi: 10.1097/j.pain.0000000000000156. [ DOI ] [ PubMed ] [ Google Scholar ] 66. Noorani A., Hung P.S., Zhang J.Y., Sohng K., Laperriere N., Moayedi M., et al. Pain relief reverses hippocampal abnormalities in trigeminal neuralgia. J Pain. 2022;23(1):141–155. doi: 10.1016/j.jpain.2021.07.004. [ DOI ] [ PubMed ] [ Google Scholar ] 67. Vaculik M.F., Noorani A., Hung P.S., Hodaie M. Selective hippocampal subfield volume reductions in classic trigeminal neuralgia. Neuroimage Clin. 2019;23 doi: 10.1016/j.nicl.2019.101911. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 68. Desouza D.D., Moayedi M., Chen D.Q., Davis K.D., Hodaie M. Sensorimotor and pain modulation brain abnormalities in trigeminal neuralgia: a paroxysmal, sensory-triggered neuropathic pain. PLoS One. 2013;8(6) doi: 10.1371/journal.pone.0066340. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 69. Li M., Yan J., Li S., Wang T., Zhan W., Wen H., et al. Reduced volume of gray matter in patients with trigeminal neuralgia. Brain Imaging Behav. 2017;11(2):486–492. doi: 10.1007/s11682-016-9529-2. [ DOI ] [ PubMed ] [ Google Scholar ] 70. Danyluk H., Andrews J., Kesarwani R., Seres P., Broad R., Wheatley B.M., et al. The thalamus in trigeminal neuralgia: structural and metabolic abnormalities, and influence on surgical response. BMC Neurol. 2021;21(1):290. doi: 10.1186/s12883-021-02323-4. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 71. Obermann M., Rodriguez-Raecke R., Naegel S., Holle D., Mueller D., Yoon M.S., et al. Gray matter volume reduction reflects chronic pain in trigeminal neuralgia. Neuroimage. 2013;74:352–358. doi: 10.1016/j.neuroimage.2013.02.029. [ DOI ] [ PubMed ] [ Google Scholar ] 72. Chen T.Y., Ko C.C., Wu T.C., Lin L.C., Shih Y.J., Hung Y.C., et al. Longitudinal alterations of the cisternal segment of trigeminal nerve and brain pain-matrix regions in patients with trigeminal neuralgia before and after treatment. BMC Neurosci. 2021;22(1):77. doi: 10.1186/s12868-021-00681-w. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 73. Zhang Y., Wang X., Wang X., Huang G. The alteration of the sensorimotor network in trigeminal neuralgia after microvascular decompression surgery: a follow-up study using independent component analysis. Front Physiol. 2025;16 doi: 10.3389/fphys.2025.1633028. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 74. Zhang Y., Mao Z., Pan L., Ling Z., Liu X., Zhang J., et al. Dysregulation of Pain- and emotion-related networks in trigeminal neuralgia. Front Hum Neurosci. 2018;12:107. doi: 10.3389/fnhum.2018.00107. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 75. Liu H., Zheng R., Zhang Y., Zhang B., Hou H., Cheng J., et al. Alterations of degree centrality and functional connectivity in classic trigeminal neuralgia. Front Neurosci. 2022;16 doi: 10.3389/fnins.2022.1090462. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 76. Tsai Y.H., Liang X., Yang J.T., Hsu L.M. Modular organization of brain resting state networks in patients with classical trigeminal neuralgia. Neuroimage Clin. 2019;24 doi: 10.1016/j.nicl.2019.102027. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 77. Zhang Y., Mao Z., Pan L., Ling Z., Liu X., Zhang J., et al. Frequency-specific alterations in cortical rhythms and functional connectivity in trigeminal neuralgia. Brain Imaging Behav. 2019;13(6):1497–1509. doi: 10.1007/s11682-019-00105-8. [ DOI ] [ PubMed ] [ Google Scholar ] 78. Li L., Du H., Li X.Y., Yu C.M., Huang B.B., Ma Z.T., et al. A study of brain function changes in patients with trigeminal neuralgia of different laterality based on rs-fMRI. J Oral Facial Pain Headache. 2025;39(1):148–156. doi: 10.22514/jofph.2025.015. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 79. Senapati A.K., Huntington P.J., Peng Y.B. Spinal dorsal horn neuron response to mechanical stimuli is decreased by electrical stimulation of the primary motor cortex. Brain Res. 2005;1036(1-2):173–179. doi: 10.1016/j.brainres.2004.12.043. [ DOI ] [ PubMed ] [ Google Scholar ] 80. Islam J., Kc E., Oh B.H., Kim S., Hyun S.H., Park Y.S. Optogenetic stimulation of the motor cortex alleviates neuropathic pain in rats of infraorbital nerve injury with/without CGRP knock-down. J Headache Pain. 2020;21(1):106. doi: 10.1186/s10194-020-01174-7. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 81. Callai E.M.M., Scarabelot V.L., Fernandes Medeiros L., de Oliveira C., de Souza A., Macedo I.C., et al. Transcranial direct current stimulation (tDCS) and trigeminal pain: a preclinical study. Oral Dis. 2019;25(3):888–897. doi: 10.1111/odi.13038. [ DOI ] [ PubMed ] [ Google Scholar ] 82. Mishra A., Yang P.F., Manuel T.J., Newton A.T., Phipps M.A., Luo H., et al. Disrupting nociceptive information processing flow through transcranial focused ultrasound neuromodulation of thalamic nuclei. Brain Stimul. 2023;16(5):1430–1444. doi: 10.1016/j.brs.2023.09.013. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 83. A pilot trial of longitudinal repetitive transcranial magnetic stimulation (rTMS) for chronic neuropathic pain. 2022. https://clinicaltrials.gov/study/NCT05593237 [Internet] Available from: [ Google Scholar ] 84. Effect of noninvasive neuromodulation on chronic pain and anxiety levels in individuals with temporomandibular disorders. 2017. https://clinicaltrials.gov/study/NCT03285685 [Internet] Available from: [ Google Scholar ] 85. Bilateral vs. 2018. Unilateral transcranial magnetic stimulation of the primary motor cortex to treat chronic orofacial pain: a pilot study with a randomized controlled design. https://clinicaltrials.gov/study/NCT03710967 [Internet] Available from: [ Google Scholar ] 86. An investigation of transcranial magnetic stimulation (TMS) for trigeminal neuralgia (TGN) 2019. https://clinicaltrials.gov/study/NCT04120129 [Internet] Available from: [ Google Scholar ] 87. Transcranial magnetic stimulation and/or neurofunctional electrical acupuncture in the rehabilitation of patients with myofascial chronic pain. 2014. https://clinicaltrials.gov/study/NCT02381171 [ Google Scholar ] 88. A clinical evaluation for the management of patients with chronic neuropathic pain with cortical stimulation. 2012. https://clinicaltrials.gov/study/NCT01554332 [Internet] Available from: [ Google Scholar ] 89. Burst-deep brain stimulation of the thalamus for neuropathic facial pain and central poststroke pain: a prospective, randomized cross-over feasibility trial. 2022. https://clinicaltrials.gov/study/NCT05204472 [Internet] Available from: [ Google Scholar ] 90. Deep brain stimulation for refractory trigeminal neuralgia with a pontine lesion: a pilot study. 2022. https://clinicaltrials.gov/study/NCT05451251 [Internet] Available from: [ Google Scholar ] 91. Abdallat M., Saryyeva A., Blahak C., Wolf M.E., Weigel R., Loher T.J., et al. Centromedian-parafascicular and somatosensory thalamic deep brain stimulation for treatment of chronic neuropathic pain: a contemporary series of 40 patients. Biomedicines. 2021;9(7) doi: 10.3390/biomedicines9070731. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 92. Owen S.L., Green A.L., Nandi D.D., Bittar R.G., Wang S., Aziz T.Z. Deep brain stimulation for neuropathic pain. Acta Neurochir Suppl. 2007;97(Pt 2):111–116. doi: 10.1007/978-3-211-33081-4_13. [ DOI ] [ PubMed ] [ Google Scholar ] 93. International classification of orofacial pain, 1st edition (ICOP) Cephalalgia. 2020;40(2):129–221. doi: 10.1177/0333102419893823. [ DOI ] [ PubMed ] [ Google Scholar ] 94. Hurt R.W., Ballantine H.T., Jr. Stereotactic anterior cingulate lesions for persistent pain: a report on 68 cases. Clin Neurosurg. 1974;21:334–351. doi: 10.1093/neurosurgery/21.cn_suppl_1.334. [ DOI ] [ PubMed ] [ Google Scholar ] 95. Foltz E.L., White L.E. The role of rostral cingulumotomy in "pain" relief. Int J Neurol. 1968;6(3-4):353–373. [ PubMed ] [ Google Scholar ] 96. Wilkinson H.A., Davidson K.M., Davidson R.I. Bilateral anterior cingulotomy for chronic noncancer pain. Neurosurgery. 1999;45(5):1129–1134. doi: 10.1097/00006123-199911000-00023. discussion 34-6. [ DOI ] [ PubMed ] [ Google Scholar ] 97. Sharim J., Pouratian N. Anterior cingulotomy for the treatment of chronic intractable pain: a systematic review. Pain Physician. 2016;19(8):537–550. [ PubMed ] [ Google Scholar ] 98. Urgosik D., Liscak R. Medial gamma knife thalamotomy for intractable pain. J Neurosurg. 2018;129(Suppl1):72–76. doi: 10.3171/2018.7.GKS181583. [ DOI ] [ PubMed ] [ Google Scholar ] 99. Leal-Isaza J.P., Molina-Romero O.I., Diez-Palma J.C., Fonnegra-Caballero A., Hernandez A.S., Ramirez-Melo L.D., et al. Effectiveness of thalamotomy with gamma knife radiosurgery as a multitarget strategy in patients with complex trigeminal neuralgia. Surg Neurol Int. 2024;15:403. doi: 10.25259/SNI_562_2024. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 100. Ishaque M., Moosa S., Urban L., Kundu B., Qureshi Z., Spears T., et al. Bilateral focused ultrasound medial thalamotomies for trigeminal neuropathic pain: a randomized controlled study. J Neurosurg. 2024;140(6):1799–1809. doi: 10.3171/2023.10.JNS23661. [ DOI ] [ PubMed ] [ Google Scholar ] 101. Gallay M.N., Magara A.E., Moser D., Kowalski M., Kaeser M., Jeanmonod D. Magnetic resonance-guided focused ultrasound central lateral thalamotomy against chronic and therapy-resistant neuropathic pain: retrospective long-term follow-up analysis of 63 interventions. J Neurosurg. 2023;139(3):615–624. doi: 10.3171/2023.1.JNS222879. [ DOI ] [ PubMed ] [ Google Scholar ] 102. Yamgoue Y., Pralong E., Levivier M., Bloch J. Deep brain stimulation of the ventroposteromedial (VPM) thalamus 10 years after VPM thalamotomy to treat a recurrent facial pain. Stereotact Funct Neurosurg. 2016;94(2):118–122. doi: 10.1159/000444762. [ DOI ] [ PubMed ] [ Google Scholar ] 103. Sozer A., Yaman M.E., Emmez H., Kale A., Guner E., Ozguven H.D., et al. Staged cingulotomy and capsulotomy for trigeminal neuropathic pain: a case report. Exp Ther Med. 2025;29(6):120. doi: 10.3892/etm.2025.12870. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 104. Villalba-Martinez G., Jimenez A.G. Are we underestimating the neuromodulation of the affective component of pain? Neuromodulation. 2025 doi: 10.1016/j.neurom.2025.07.007. [ DOI ] [ PubMed ] [ Google Scholar ] 105. Gallay M.N., Moser D., Jeanmonod D., MR-Guided Focused Ultrasound Central Lateral Thalamotomy for Trigeminal Neuralgia Single center experience. Front Neurol. 2020;11:271. doi: 10.3389/fneur.2020.00271. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 106. Yuen J., Khayat H., Fakhroo F.A., Buongermini R., Germann J., Boutet A., et al. Is it safe to have deep brain stimulation after MRI-guided focused ultrasound ablation? A report of three cases and review of literature. Stereotact Funct Neurosurg. 2026:1–17. doi: 10.1159/000551355. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 107. Yuen J., Goyal A., Kaufmann T.J., Jackson L.M., Miller K.J., Klassen B.T., et al. Comparison of the impact of skull density ratio with alternative skull metrics on magnetic resonance-guided focused ultrasound thalamotomy for tremor. J Neurosurg. 2023;138(1):50–57. doi: 10.3171/2022.5.JNS22350. [ DOI ] [ PubMed ] [ Google Scholar ] 108. Yuen J., Miller K.J., Klassen B.T., Lehman V.T., Lee K.H., Kaufmann T.J. Hyperostosis in combination with low skull density ratio: a potential contraindication for magnetic resonance imaging-guided focused ultrasound thalamotomy. Mayo Clin Proc Innov Qual Outc. 2022;6(1):10–15. doi: 10.1016/j.mayocpiqo.2021.11.007. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 109. Buchanan R.J., Darrow D., Monsivais D., Nadasdy Z., Gjini K. Motor cortex stimulation for neuropathic pain syndromes: a case series experience. Neuroreport. 2014;25(9):715–717. doi: 10.1097/WNR.0000000000000174. [ DOI ] [ PubMed ] [ Google Scholar ] 110. Raslan A.M., Nasseri M., Bahgat D., Abdu E., Burchiel K.J. Motor cortex stimulation for trigeminal neuropathic or deafferentation pain: an institutional case series experience. Stereotact Funct Neurosurg. 2011;89(2):83–88. doi: 10.1159/000323338. [ DOI ] [ PubMed ] [ Google Scholar ] 111. Bazarra Castro G.J., González-Escamilla G., Macho C.M., Pohlen A.M., Segura A.M., Álvarez-Sala A., et al. Targeting the centromedian nucleus of the thalamus for epilepsy. Brain Network Disorders. 2025;1(2):65–70. [ Google Scholar ] 112. Singh H., Stamm M., Warren A.E.L., Kulsomphob A., Jha R., Bhatia N., et al. Optimizing indirect targeting of the centromedian nucleus for deep brain stimulation by incorporating third ventricular anatomy. J Neurosurg. 2025;142(2):299–310. doi: 10.3171/2024.4.JNS24286. [ DOI ] [ PubMed ] [ Google Scholar ] 113. Hosobuchi Y., Adams J.E., Rutkin B. Chronic thalamic stimulation for the control of facial anesthesia dolorosa. Arch Neurol. 1973;29(3):158–161. doi: 10.1001/archneur.1973.00490270040005. [ DOI ] [ PubMed ] [ Google Scholar ] 114. Levy R.M., Lamb S., Adams J.E. Treatment of chronic pain by deep brain stimulation: long term follow-up and review of the literature. Neurosurgery. 1987;21(6):885–893. doi: 10.1227/00006123-198712000-00017. [ DOI ] [ PubMed ] [ Google Scholar ] 115. Martin E., Aubry J.F., Schafer M., Verhagen L., Treeby B., Pauly K.B. ITRUSST consensus on standardised reporting for transcranial ultrasound stimulation. Brain Stimul. 2024;17(3):607–615. doi: 10.1016/j.brs.2024.04.013. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 116. Darmani G., Bergmann T.O., Butts Pauly K., Caskey C.F., de Lecea L., Fomenko A., et al. Non-invasive transcranial ultrasound stimulation for neuromodulation. Clin Neurophysiol. 2022;135:51–73. doi: 10.1016/j.clinph.2021.12.010. [ DOI ] [ PubMed ] [ Google Scholar ] 117. Sarica C., Nankoo J.F., Fomenko A., Grippe T.C., Yamamoto K., Samuel N., et al. Human studies of transcranial ultrasound neuromodulation: a systematic review of effectiveness and safety. Brain Stimul. 2022;15(3):737–746. doi: 10.1016/j.brs.2022.05.002. [ DOI ] [ PubMed ] [ Google Scholar ] 118. Martin E., Roberts M., Grigoras I.F., Wright O., Nandi T., Rieger S.W., et al. Ultrasound system for precise neuromodulation of human deep brain circuits. Nat Commun. 2025;16(1):8024. doi: 10.1038/s41467-025-63020-1. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 119. Riis T.S., Feldman D.A., Losser A.J., Okifuji A., Kubanek J. Noninvasive targeted modulation of pain circuits with focused ultrasonic waves. Pain. 2024;165(12):2829–2839. doi: 10.1097/j.pain.0000000000003322. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 120. Boccard S.G.J., Prangnell S.J., Pycroft L., Cheeran B., Moir L., Pereira E.A.C., et al. Long-term results of deep brain stimulation of the anterior cingulate cortex for neuropathic pain. World Neurosurg. 2017;106:625–637. doi: 10.1016/j.wneu.2017.06.173. [ DOI ] [ PubMed ] [ Google Scholar ] 121. Badran B.W., Caulfield K.A., Stomberg-Firestein S., Summers P.M., Dowdle L.T., Savoca M., et al. Sonication of the anterior thalamus with MRI-guided transcranial focused ultrasound (tFUS) alters pain thresholds in healthy adults: a double-blind, sham-controlled study. Focus. 2022;20(1):90–99. doi: 10.1176/appi.focus.20109. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 122. Goyal A., Goetz S., Stanslaski S., Oh Y., Rusheen A.E., Klassen B., et al. The development of an implantable deep brain stimulation device with simultaneous chronic electrophysiological recording and stimulation in humans. Biosens Bioelectron. 2021;176 doi: 10.1016/j.bios.2020.112888. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 123. Zhang Q., Xiao Z., Huang C., Hu S., Kulkarni P., Martinez E., et al. Local field potential decoding of the onset and intensity of acute pain in rats. Sci Rep. 2018;8(1):8299. doi: 10.1038/s41598-018-26527-w. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 124. Lenz F.A., Dougherty P.M., Meeker T.J., Saffer M.I., Oishi K. Neuroscience of the human thalamus related to acute pain and chronic "thalamic" pain. J Neurophysiol. 2024;132(6):1756–1778. doi: 10.1152/jn.00065.2024. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 125. Shin H., Scheitler K.M., Rojas Cabrera J.M., Goyal A., Boesche J.B., Rusheen A.E., et al. A multimodal platform for real-time neurochemical and electrophysiologic monitoring for intraoperative neurosurgical applications. Biosens Bioelectron. 2025 doi: 10.1016/j.bios.2025.118151. [ DOI ] [ PubMed ] [ Google Scholar ] 126. Saitoh Y., Hirayama A., Kishima H., Oshino S., Hirata M., Kato A., et al. Stimulation of primary motor cortex for intractable deafferentation pain. Acta Neurochir Suppl. 2006;99:57–59. doi: 10.1007/978-3-211-35205-2_11. [ DOI ] [ PubMed ] [ Google Scholar ] 127. Fricova J., Klirova M., Masopust V., Novak T., Verebova K., Rokyta R. 2013. p. S125. (Repetitive transcranial magnetic stimulation in the treatment of chronic orofacial pain). s34. [ DOI ] [ PubMed ] [ Google Scholar ] 128. Ayache S.S., Ahdab R., Chalah M.A., Farhat W.H., Mylius V., Goujon C., et al. Analgesic effects of navigated motor cortex rTMS in patients with chronic neuropathic pain. Eur J Pain. 2016;20(9):1413–1422. doi: 10.1002/ejp.864. [ DOI ] [ PubMed ] [ Google Scholar ] 129. Poydasheva A.G., Sinitsyn D.O., Bakulin I.S., Suponeva N.A., Piradov M.A. vol. 3. 2021. pp. 49–56. (Structural and functional biomarkers of efficacy of navigated repetitive transcranial magnetic stimulation in therapy for trigeminal neuralgia). [ Google Scholar ] 130. Nuti C., Peyron R., Garcia-Larrea L., Brunon J., Laurent B., Sindou M., et al. Motor cortex stimulation for refractory neuropathic pain: four year outcome and predictors of efficacy. Pain. 2005;118(1-2):43–52. doi: 10.1016/j.pain.2005.07.020. [ DOI ] [ PubMed ] [ Google Scholar ] 131. Pirotte B., Voordecker P., Neugroschl C., Baleriaux D., Wikler D., Metens T., et al. Combination of functional magnetic resonance imaging-guided neuronavigation and intraoperative cortical brain mapping improves targeting of motor cortex stimulation in neuropathic pain. Neurosurgery. 2005;56(2 Suppl):344–359. doi: 10.1227/01.neu.0000144837.31665.29. discussion -59. [ DOI ] [ PubMed ] [ Google Scholar ] 132. Pirotte B., Neugroschl C., Metens T., Wikler D., Denolin V., Voordecker P., et al. Comparison of functional MR imaging guidance to electrical cortical mapping for targeting selective motor cortex areas in neuropathic pain: a study based on intraoperative stereotactic navigation. AJNR Am J Neuroradiol. 2005;26(9):2256–2266. [ PMC free article ] [ PubMed ] [ Google Scholar ] 133. Rasche D., Ruppolt M., Stippich C., Unterberg A., Tronnier V.M. Motor cortex stimulation for long-term relief of chronic neuropathic pain: a 10 year experience. Pain. 2006;121(1-2):43–52. doi: 10.1016/j.pain.2005.12.006. [ DOI ] [ PubMed ] [ Google Scholar ] 134. Lefaucheur J.P., Drouot X., Cunin P., Bruckert R., Lepetit H., Créange A., et al. Motor cortex stimulation for the treatment of refractory peripheral neuropathic pain. Brain. 2009;132(Pt 6):1463–1471. doi: 10.1093/brain/awp035. [ DOI ] [ PubMed ] [ Google Scholar ] 135. Nguyen J.P., Lefaucheur J.P., Raoul S., Roualdes V., Péréon Y., Keravel Y. In: Neuromodulation. Krames E.S., Peckham P.H., Rezai A.R., editors. Academic Press; San Diego: 2009. Chapter 40 - motor cortex stimulation for the treatment of neuropathic pain; pp. 515–526. [ Google Scholar ] 136. Fagundes-Pereyra W.J., Teixeira M.J., Reyns N., Touzet G., Dantas S., Laureau E., et al. Motor cortex electric stimulation for the treatment of neuropathic pain. Arq Neuropsiquiatr. 2010;68(6):923–929. doi: 10.1590/s0004-282x2010000600018. [ DOI ] [ PubMed ] [ Google Scholar ] 137. Maarrawi J., Peyron R., Mertens P., Costes N., Magnin M., Sindou M., et al. Brain opioid receptor density predicts motor cortex stimulation efficacy for chronic pain. Pain. 2013;154(11):2563–2568. doi: 10.1016/j.pain.2013.07.042. [ DOI ] [ PubMed ] [ Google Scholar ] 138. Andre-Obadia N., Mertens P., Lelekov-Boissard T., Afif A., Magnin M., Garcia-Larrea L. Is life better after motor cortex stimulation for pain control? Results at long-term and their prediction by preoperative rTMS. Pain Physician. 2014;17(1):53–62. [ PubMed ] [ Google Scholar ] 139. Delavallee M., Finet P., de Tourtchaninoff M., Raftopoulos C. Subdural motor cortex stimulation: feasibility, efficacy and security on a series of 18 consecutive cases with a follow-up of at least 3 years. Acta Neurochir. 2014;156(12):2289–2294. doi: 10.1007/s00701-014-2240-4. [ DOI ] [ PubMed ] [ Google Scholar ] 140. Isagulyan E.D., Tomsky A.A., Dekopov A.V., Salova E.M., Troshina E.M., Dorokhov E.V., et al. Results of motor cortex stimulation in the treatment of chronic pain syndromes. Zh Vopr Neirokhir Im N N Burdenko. 2015;79(6):46–60. doi: 10.17116/neiro201579646-60. [ DOI ] [ PubMed ] [ Google Scholar ] 141. Slotty P.J., Eisner W., Honey C.R., Wille C., Vesper J. Long-term follow-up of motor cortex stimulation for neuropathic pain in 23 patients. Stereotact Funct Neurosurg. 2015;93(3):199–205. doi: 10.1159/000375177. [ DOI ] [ PubMed ] [ Google Scholar ] 142. Kolodziej M.A., Hellwig D., Nimsky C., Benes L. Treatment of central deafferentation and trigeminal neuropathic pain by motor cortex stimulation: report of a series of 20 patients. J Neurol Surg Cent Eur Neurosurg. 2016;77(1):52–58. doi: 10.1055/s-0035-1558419. [ DOI ] [ PubMed ] [ Google Scholar ] 143. Rasche D., Tronnier V.M. Clinical significance of invasive motor cortex stimulation for trigeminal facial neuropathic pain syndromes. Neurosurgery. 2016;79(5):655–666. doi: 10.1227/NEU.0000000000001353. [ DOI ] [ PubMed ] [ Google Scholar ] 144. Zhang X., Hu Y., Tao W., Zhu H., Xiao D., Li Y. The effect of motor cortex stimulation on central poststroke pain in a series of 16 patients with a mean Follow-Up of 28 months. Neuromodulation. 2017;20(5):492–496. doi: 10.1111/ner.12547. [ DOI ] [ PubMed ] [ Google Scholar ] 145. Henssen D., Kurt E., van Cappellen van Walsum A.M., Arnts I., Doorduin J., Kozicz T., et al. Long-term effect of motor cortex stimulation in patients suffering from chronic neuropathic pain: an observational study. PLoS One. 2018;13(1) doi: 10.1371/journal.pone.0191774. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 146. Hamani C., Fonoff E.T., Parravano D.C., Silva V.A., Galhardoni R., Monaco B.A., et al. Motor cortex stimulation for chronic neuropathic pain: results of a double-blind randomized study. Brain. 2021;144(10):2994–3004. doi: 10.1093/brain/awab189. [ DOI ] [ PubMed ] [ Google Scholar ] 147. Siegfried J. Monopolar electrical stimulation of nucleus ventroposteromedialis thalami for postherpetic facial pain. Appl Neurophysiol. 1982;45(1-2):179–184. doi: 10.1159/000101595. [ DOI ] [ PubMed ] [ Google Scholar ] 148. Kumar K., Toth C., Nath R.K. Deep brain stimulation for intractable pain: a 15-year experience. Neurosurgery. 1997;40(4):736–746. doi: 10.1097/00006123-199704000-00015. discussion 46-7. [ DOI ] [ PubMed ] [ Google Scholar ] 149. Nandi D., Aziz T., Carter H., Stein J. Thalamic field potentials in chronic central pain treated by periventricular gray stimulation -- a series of eight cases. Pain. 2003;101(1-2):97–107. doi: 10.1016/s0304-3959(02)00277-4. [ DOI ] [ PubMed ] [ Google Scholar ] 150. Broggi G., Franzini A., Leone M., Bussone G. Update on neurosurgical treatment of chronic trigeminal autonomic cephalalgias and atypical facial pain with deep brain stimulation of posterior hypothalamus: results and comments. Neurol Sci. 2007;28(Suppl 2):S138–S145. doi: 10.1007/s10072-007-0767-3. [ DOI ] [ PubMed ] [ Google Scholar ] 151. Franzini A., Leone M., Messina G., Cordella R., Marras C., Bussone G., et al. Neuromodulation in treatment of refractory headaches. Neurol Sci. 2008;29(Suppl 1):S65–S68. doi: 10.1007/s10072-008-0891-8. [ DOI ] [ PubMed ] [ Google Scholar ] 152. Cordella R., Franzini A., La Mantia L., Marras C., Erbetta A., Broggi G. Hypothalamic stimulation for trigeminal neuralgia in multiple sclerosis patients: efficacy on the paroxysmal ophthalmic pain. Mult Scler. 2009;15(11):1322–1328. doi: 10.1177/1352458509107018. [ DOI ] [ PubMed ] [ Google Scholar ] 153. Sims-Williams H.P., Javed S., Pickering A.E., Patel N.K. Characterising the analgesic effect of different targets for deep brain stimulation in trigeminal anaesthesia dolorosa. Stereotact Funct Neurosurg. 2016;94(3):174–181. doi: 10.1159/000446608. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 154. Boccard S.G., Pereira E.A., Aziz T.Z. Deep brain stimulation for chronic pain. J Clin Neurosci. 2015;22(10):1537–1543. doi: 10.1016/j.jocn.2015.04.005. [ DOI ] [ PubMed ] [ Google Scholar ] 155. Tomycz N.D., Deibert C.P., Moossy J.J. Cervicomedullary junction spinal cord stimulation for head and facial pain. Headache. 2011;51(3):418–425. doi: 10.1111/j.1526-4610.2010.01829.x. [ DOI ] [ PubMed ] [ Google Scholar ] 156. Chivukula S., Tempel Z.J., Weiner G.M., Gande A.V., Chen C.J., Ding D., et al. Cervical and cervicomedullary spinal cord stimulation for chronic pain: efficacy and outcomes. Clin Neurol Neurosurg. 2014;127:33–41. doi: 10.1016/j.clineuro.2014.09.023. [ DOI ] [ PubMed ] [ Google Scholar ] 157. Basha A., Simry H.A.M., Abdelbar A.E., Sabry H., Raslan A.M. Outcome of surgical treatments of chronic pain caused by trigeminal neuropathy. World Neurosurg. 2023;170:e57–e69. doi: 10.1016/j.wneu.2022.10.057. [ DOI ] [ PubMed ] [ Google Scholar ] 158. Edelbach B.M., Lopez-Gonzalez M.A. Percutaneous high cervical spinal cord stimulation for refractory trigeminal neuralgia. Surg Neurol Int. 2023;14:198. doi: 10.25259/SNI_60_2023. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 159. Malik A., D'Souza R.S., Karri J., Javed S. Cervical spinal cord stimulation for treatment of sympathetically mediated orofacial pain: case series and narrative review. Neuromodulation. 2024;27(8):1321–1329. doi: 10.1016/j.neurom.2024.09.008. [ DOI ] [ PubMed ] [ Google Scholar ] 160. Fricova J., Englerova K., Rokyta R. Noninvasive transcranial direct current stimulation (tDCS) for the treatment of orofacial pain. Neuroendocrinol Lett. 2016;37(5):368–372. [ PubMed ] [ Google Scholar ] 161. Alanazi F.I., Bravo C.A.R., Moreno J.S.S., Botero-Posada L.F., Ladino L.D., Rios A.L.L., et al. Modulation of neuronal activity in human centromedian nucleus during an auditory attention and working memory task. Neuroimage. 2024;296 doi: 10.1016/j.neuroimage.2024.120686. [ DOI ] [ PubMed ] [ Google Scholar ] Articles from Neurotherapeutics are provided here courtesy of Elsevier ACTIONS View on publisher site PDF (1.8 MB) Cite Collections Permalink PERMALINK Copy RESOURCES Similar articles Cited by other articles Links to NCBI Databases Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM Add to Collections Create a new collection Add to an existing collection Name your collection * Choose a collection Unable to load your collection due to an error Please try again Add Cancel Follow NCBI NCBI on X (formerly known as Twitter) NCBI on Facebook NCBI on LinkedIn NCBI on GitHub NCBI RSS feed Connect with NLM NLM on X (formerly known as Twitter) NLM on Facebook NLM on YouTube National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers NLM NIH HHS USA.gov Back to Top

Related documents

• Reduced susceptibility to triclosan and proposed epidemiological cut-off values for disinfectants and heavy metals in Escherichia coli isolated from Thai tilapia farms: Implications for One Health antimicrobial resistance surveillance.#1039988
• Edible coatings and films in meat preservation: Materials, functional mechanisms, and technological challenges.#1039989
• Palm Vein Biometrics A Rapid Patient Identification Tool for Emergency and Trauma Care.#1039990
• Directions for Establishing a Korean National One Health Joint Plan of Action: Focusing on Zoonotic Disease Preparedness and Response.#1039991
• Intensive arable farming calls for resilient wild bee restoration amid severe abundance fluctuations.#1039992