Exploration by NMR Spectroscopy of the Choline Concentrations in the Insular Cortex of Patients Suffering of Neuropathic Pain Induced by Oxaliplatin

Neurotoxic chemotherapy, including oxaliplatin, are responsible for very disabling neuropathic pain that can last for months or even years after the end of chemotherapy. Currently, there is no effective neuroprotective treatment to prevent or relieve this pain. The only strategy is the reduction of oxaliplatin doses or premature discontinuation of therapy, with the risk of burdening the prognosis for remission. Thus, a better understanding of the pathophysiology of these iatrogenic neuropathies appears necessary in order to discover new potential therapeutic targets. Preclinical works were able to demonstrate important metabolic changes in certain brain structures in an animal model of oxaliplatin-induced neuropathy. A significant increase of choline concentration has been found in the posterior insular cortex of neuropathic animals compared with control animals. Furthermore, the concentrations of choline were positively correlated to nociceptive thresholds. Thus, neuropathic pain induced by oxaliplatin would involve the posterior insular cortex and would be associated with an increase in choline concentration at this level. Clinical translation of these preclinical results is feasible in practice since choline concentration can be determined in the brain by non-invasive magnetic resonance spectroscopy.