Evaluation of Vanilloid Receptor Inactivation for Preemptive Analgesia

Successful preemptive analgesic strategies are superior to traditional pain management schemes in the management of post-operative pain. The premise of this double-blind, placebo and positive-controlled clinical study is to evaluate the efficacy of vanilloid agonists as preemptive agents in an oral surgery tissue injury model. Vanilloids are a class of small organic compounds; the most familiar of which is capsaicin, the active ingredient in hot pepper. Binding of capsaicin to the vanilloid-1 receptor produces initial activation and then long-acting desensitization of pain specific neurons. We propose to produce a selective, long-term inactivation of peripheral pain transmission through the local application of capsaicin in the oral mucosa in an effort to prevent or reduce post-operative pain in the oral surgery model. Healthy subjects will be recruited, and following local anesthesia and conscious sedation, will be given an intramucosal injection of either capsaicin or placebo, or as a positive control, intravenous ketorolac. Subjects will rate pain and time of analgesic rescue medication request will be noted. Small biopsies will be removed from the extraction site prior to drug injection and at 48 hr post-operatively. Tissue levels of neurogenic inflammatory mediators and sensory neuron content will be compared pre- and post-operatively. A decrease in post-operative pain and decrease in analgesic use will be taken as a positive effect of the vanilloid for decreasing post-operative pain. We anticipate that through the long term blockade of pain specific fibers pre-operatively that there will be significant attenuation of post-operative pain development following surgery. This has significant implications for reducing pain and suffering, decreasing analgesic use, and reducing post-operative complications following surgery.