PHARMACOLOGICAL EVIDENCE FOR THE INVOLVEMENT OF THE ENDOGENOUS OPIOIDSYSTEM IN THE RESPONSE TO LOCAL INFLAMMATION IN THE RAT PAW

We have investigated the role of the endogenous opioid system (EOS) on the inflammatory response induced by subplantar (s.p.) injection of s aline (SS) and carrageenan (CA) in the hindpaw of the rat. The adminis tration of intraperitoneal (i.p.) naloxone was used in order to unmask the effects of endogenous opiates released during peripheral inflamma tion. Three groups of rats received one of the following s.p. treatmen ts: SS, CA, or no injection (NI). Pain pressure threshold (PPT), paw v olume (edema) and local temperature were evaluated in baseline conditi ons and 3 h after treatment. In each group, the effects of i.p. vehicl e, naloxone and (+)-naloxone (0.1 mg/kg) were also investigated. Both SS and CA induced a significant inflammatory response with hyperalgesi a, edema and local hyperthermia. The i.p. administration of naloxone b ut not that of (+)-naloxone 15 min prior to testing, significantly inc reased edema in all groups of treatment (P<0.05), without altering PPT or local temperature. Two-way ANOVA revealed that treatment and drugs , as well as their interaction, had a significant impact on edema whic h was related to the effects of CA and naloxone. Our findings illustra te the involvement of the EOS in the physiological response to local i njury, regulating microvascular leakage in the inflamed tissues.