Pharmacological evidence for the involvement of the endogenous opioid system 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 saline (SS) and carrageenan (CA) in the hindpaw of the rat. The administration of intraperitoneal (i.p.) naloxone was used in order to unmask the effects of endogenous opiates released during peripheral inflammation. Three groups of rats received one of the following s.p. treatments: SS, CA, or no injection (NI). Pain pressure threshold (PPT), paw volume (edema) and local temperature were evaluated in baseline conditions and 3 h after treatment. In each group, the effects of i.p. vehicle, naloxone and (+)-naloxone (0.1 mg/kg) were also investigated. Both SS and CA induced a significant inflammatory response with hyperalgesia, edema and local hyperthermia. The i.p. administration of naloxone but not that of (+)-naloxone 15 min prior to testing, significantly increased 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 which was related to the effects of CA and naloxone. Our findings illustrate the involvement of the EOS in the physiological response to local injury, regulating microvascular leakage in the inflamed tissues.