Ligation of the infraorbital nerve: a model of trigeminal neuropathic pain?

Neuropathic pain has different physiopharmacological characteristics at the cephalic (trigeminal nerve territory) versus the extracephalic (innervated through spinal networks) level. In particular, drugs that effectively reduce extracephalic neuropathic pain such as antidepressants, some anticonvulsants such as gabapentin and pregabalin, inhibitors of voltage-gated sodium channels and even opiates are generally less effective against cephalic neuropathic pain. Conversely, drugs which alleviate cephalic neuropathic pain such as carbamazepine and oxcarbamazepine are only poorly active against extracephalic neuropathic pain. Thorough studies of these physiopharmacological differences can be made thanks to the use of validated animal models that consist of the unilateral ligature of the sciatic nerve versus the infraorbital nerve. Accordingly, antimigraine drugs that belong to the triptan class (mixed agonists at serotonin 5-HT1B, 5-HT1D, 5-HT1F receptors) or the gepant class (antagonists at CGRP receptors) were found to reduce mechanical allodynia evoked by infraorbital nerve ligature but to be essentially inactive against allodynia/hyperalgesia caused by sciatic nerve ligature. Thorough studies of neuroplastic phenomena underlying neuronal sensitization after ligature-induced nerve injury showed marked regional differences, in line with differences in the response to various drugs noted above. Such studies should allow the identification of novel molecular targets of potential therapeutic interest for alleviating neuropathic pain in cephalic and/or extracephalic territories.