Naloxone reverses the antinociceptive action of clonidine in spontaneously hypertensive rats.

Earlier studies have shown that the antihypertensive action of clonidine is reversed by naloxone in hypertensive (SHR), but not in normotensive rats (WKY). We investigated the effects of clonidine and naloxone on pain sensitivity of SHR and WKY by using the formalin test (FT) and the tail-flick test (TFT). Using the FT, basal pain sensitivity was similar in SHR and WKY. Clonidine produced dose-dependent analgesia (0.03-0.15 mg/kg i.p.), and it was more potent in SHR than in WKY. The effect of clonidine was partially antagonized by naloxone (2 mg/kg i.p.) in SHR, but not in WKY. Naloxone alone caused moderate analgesia in SHR and no effect in WKY. Using the TFT, SHR displayed a naloxone-reversible decrease in basal pain sensitivity, when compared to WKY. Clonidine was ineffective (WKY) or caused moderate hyperalgesia (SHR). These results indicate that the two pain tests activate different pain controlling mechanisms, with different sensitivity to the antinociceptive action of clonidine. In SHR, this action seems to involve the release of endogenous opioids.