Capsaicin avoidance as a measure of chemical hyperalgesia in orofacial nerve injury models

Many patients suffer from trigeminal neuralgia and other types of orofacial pain that are poorly treated, necessitating preclininal animal models for development of mechanisms-based therapies. The present study assessed capsaicin avoidance and other nocifensive behavioral responses in three models of orofacial nerve injury in rats: chronic constriction injury (CCI) of the mental nerves, partial tight ligation of mental nerves, and CCI of lingual nerves. We additionally investigated if nerve injury resulted in enhanced capsaicin-evoked activation of neurons in trigeminal caudalis (Vc) or nucleus of the solitary tract (NTS) based on expression of Fos-like immunoreactivity (FLI). Mental nerve CCI resulted in an enhancement of capsaicin avoidance in a two-bottle preference paradigm, while neither mental nerve injury produced thermal hyperalgesia or mechanical allodynia. CCI of lingual nerves did not affect capsaicin avoidance. Counts of FLI in Vc were significantly higher in the lingual sham and mental nerve CCI groups compared to mental shams; FLI counts in NTS did not differ among groups. Mental nerve CCI may have induced central sensitization of chemical nociception since increased capsaicin avoidance was accompanied by greater activation of Vc neurons in response to oral capsaicin.