Involvement of endogenous opioid system in scorpion toxin-induced antinociception in mice

The present study analyzes the involvement of the endogenous opioid system in the antinociceptive effects produced in mammals after α- or β- scorpion toxin injections. The analgesic effects on mice of the α-anatoxin Amm VIII, a weak modulator of Nav1.2 channel, and the depressant insect-selective β-toxin LqqIT2 were evaluated by intraperitoneal route. The two toxins increased hot plate and tail flick latencies in a dose-dependent manner. We also compared the effects of the toxins with those obtained after acetic acid administration or cold-water tail immersion, which both induce pain relief through the activation of diffuse noxious inhibitory controls (DNIC) and the release of endogenous opioids. The increased latencies obtained with the toxins, acetic acid, or cold-water tail immersion were partly reversed by the co-administration of the opioid receptor antagonist naloxone. Finally, AmmVIII, LqqIT2, or acetic acid, induced increased c-fos mRNA expression in spinal cord. This increase disappeared when the toxins were co-injected with acetic acid. In conclusion, we show for the first time that an α-anatoxin exhibits a potent analgesic activity and confirm that depressant β-toxins are able to reduce nociception. We hypothesize that pain relief induced by these scorpion toxins may implicate the activation of an endogenous opioid system and may be partly the result of a counter irritation phenomenon, which could be due to the activation of DNIC.