Local administration of mu or kappa opioid agonists attenuates capsaicin-induced thermal hyperalgesia via peripheral opioid receptors in rats

Rationale: By acting on peripheral opioid receptors, opioid agonists can at tenuate nociceptive responses induced by a variety of agents. Objectives: T his study was conducted to characterize capsaicin-induced thermal hyperalge sia in rats and to evaluate the hypothesis chat local administration of eit her mu or kappa opioid agonists (fentanyl and U50,488, respectively) can at tenuate capsaicin-induced nociception. Methods: Capsaicin was administered s.c. in the tail of rats to evoke a nociceptive response, which was measure d by the warm-water tail-withdrawal procedure. Either fentanyl or U50,488 w as co-administered with capsaicin in the tail to evaluate local antinocicep tive effects. In addition, the local antagonism study was performed to conf irm the site of action of both opioid agonists. Results: Capsaicin (0.3-10 mu g) dose dependently produced thermal hyperalgesia manifested as reduced tail-withdrawal latencies in 45 degrees C water. Go-administration of eithe r fentanyl (0.32-3.2 mu g) or U50,488 (10-100 mu g) with capsaicin (3 mu g) attenuated capsaicin-induced hyperalgesia in a dose-dependent manner. Furt hermore, this local antinociception was antagonized by small doses (10-100 mu g) of an opioid antagonist, quadazocine, applied s.c. in the tail. Howev er, the locally effective doses of quadazocine, when applied s.c. in the ba ck (i.e., around the scapular region), did not antagonize either fentanyl o r U50,488. Conclusions: In this experimental pain model, activation of peri pheral mu or kappa opioid receptors can attenuate capsaicin-induced thermal hyperalgesia in rats. It supports the notion that peripheral antinocicepti on can be achieved by local administration of analgesics into the injured t issue without producing central side effects.