The Effect of Clonidine Pretreatment on Epidural Resiniferatoxin in a Neuropathic Pain Rat Model

Resiniferatoxin (RTX) is an ultrapotent synthetic TRPV1 (transient receptor potential vanilloid subtype 1) agonist with significant initial transient hyperalgesia followed by a prolonged analgesic effect in response to thermal stimulus. Using a rat model of neuropathic pain, we evaluated the effect of pretreatment with clonidine which has been shown to relieve intradermal capsaicin-induced hyperalgesia-on the initial hyperalgesic response and the thermal analgesic property of RTX. Thirty-six male rats were divided into 6 treatment groups (n = 6 each): RTX 500 ng, RTX tug, clonidine 20 mu g (Cl), Cl+RTX 500 ng, Cl+RTX mu g, or normal saline 20 mu L (control). We evaluated the short-term (180min) and long-term (20 days) analgesic effects of RTX after thermal stimulation and mechanical stimulation. RTX had significant initial transient hyperalgesia followed by a prolonged analgesic effect in response to the thermal stimulus, but the RTX 500 ng and RTX mu g groups showed no initial short-term thermal hyperalgesic responses when pretreated with clonidine. The Cl+RTX mu g rats' behavior scores indicated that they were more calm and comfortable compared to the RTX 1 mu g rats. Even though we cannot precisely confirm that pretreatment with clonidine potentiates or adds to the analgesic effect of RTX, clonidine pretreatment with epidural RTX eliminated the initial RTX-associated hyperalgesic response and systemic toxicity in this neuropathic pain rat model.