Targeting Peripheral and Central Sensitization of Morton’s Neuroma Pain

Patients suffering from peripheral neuropathic pain often experience inadequate pain relief. Morton’s neuroma (MN), which is caused by a localized nerve lesion in the forefoot, represents an excellent model to study the pathology and treatment of peripheral neuropathic pain. Patients suffer from burning or stabbing pain upon weight-bearing, which limits their mobility. A significant fraction of patients continues to experience pain after non-surgical treatments. We aim to evaluate analgesic efficacy of long-term inactivation of a specific peripheral axon population that expresses TRPV1. We hypothesize that a perineural injection of the super-potent TRPV1 agonist resiniferatoxin (RTX) will selectively lesion these heat- and inflammation sensitive afferent fibers. This strategy is based on preclinical studies and successful clinical trials for patients with refractory pain. In order to investigate the involvement of these and other fiber types in MN pain, we performed quantitative sensory testing. We observed individual patterns of heat hyperalgesia across several testing locations, indicating variable nerve sensitization in the patient population. In a subset of patients heat hyperalgesia included an area outside the territory of the affected nerve and implicating processes of spinal secondary sensitization. Most MN patients showed hyperalgesia to mechanical deep tissue stimulation in both the affected and healthy foot, but not at a remote testing site. Overall, these findings suggest both sensitization of local peripheral fibers and central segmental circuits. The prevalent symptom of burning pain in MN patients reinforces the idea that RTX may provide effective pain relief in Morton’s neuroma patients.