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

Abstract

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 construction 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.

Effects of gustatory nerve transection and/or ovariectomy on oral capsaicin avoidance in rats

“…The concentration-dependent avoidance of capsaicin observed presently in female rats is consistent with our previous studies with male rats [9, 49]. A salient finding is that CTx, with or without OVx, did not enhance capsaicin avoidance, arguing against the original hypothesis that gustatory nerve damage releases inhibition of trigeminal nociceptive pathways.…”

“…During formal testing in the 2-bottle paired preference paradigm, rats that had been water-restricted for the previous 22 hr were transferred from the home cage to the metal box. The sipper tube of each bottle, and the floor of the metal box, were connected to a lickometer (DM-8; Columbus Instruments, Columbus OH) to simultaneously monitor licking from each of 32 bottles (2 per cage), thus allowing us to monitor drinking from 16 rats at once [9]. Each lickometer output channel was routed to computer via an interface (Columbus Instruments) and lick counts from each bottle were registered at 1-min intervals over the 2-hr access period.…”

“…We investigated if bilateral CT transection (CTx) in rats increases their sensitivity to the irritant capsaicin using a 2-bottle avoidance paradigm [9, 49]. As the prevalence of several disorders within the area innervated by the trigeminal nerve is increased in women [13, 20], we assessed the effect of ovariectomy (OVx) in our model.…”

Taste function assessed by electrogustometry in burning mouth syndrome: a case–control study

“…Based on the hypothesis of CT dysfunction in iBMS, gustatory nerve has previously been proposed to contribute to iBMS by disinhibiting trigeminal nociceptive inputs (Bartoshuk et al , ). However, bilateral CT damage neither increased capsaicin avoidance in chronically diseased animals (Boucher et al , ) nor altered lingual nociceptive inputs after acute lesions (Boucher et al , ), arguing against a potent disinhibiting effect of gustatory afferents on nociceptive transmission in iBMS.…”

“…The discrepancy in electric taste detection within ipsilateral foliate and fungiform papillae may in this case be related to CT dysfunction. Based on the hypothesis of CT dysfunction in iBMS, gustatory nerve has previously been proposed to contribute to iBMS by disinhibiting trigeminal nociceptive inputs (Bartoshuk et al, 2005 (Boucher et al, 2013), arguing against a potent disinhibiting effect of gustatory afferents on nociceptive transmission in iBMS.…”