Sevoflurane suppresses noxious stimulus-evoked expression of Fos-like immunoreactivity in the rat spinal cord via activation of endogenous opioid systems

We investigated the antagonism of sevoflurane antinociception by opioid antagonists in the rat formalin test. Formalin injection into the hindpaw of the rat induces the nocifensive flinching behavior and the expression of Fos-like immunoreactivity (Fos-LI) in the spinal cord. Sevoflurane significantly suppressed the flinching behavior and decreased the number of Fos-LI neurons in the dorsal horn of spinal cord compared with the control group. Moreover, pretreatment with intraperitoneal naloxone plus naltrexone antagonized the suppression of flinching behavior and the decrease of the number of Fos-LI neurons produced by 3% sevoflurane. Intraperitoneal opioid antagonists themselves had no effects on both the behavior response and the expression of Fos-LI induced by formalin injection. This study supports the hypothesis that sevoflurane suppresses the nociceptive response, at least in part, by activating endogenous opioid systems.