Dextromethorphan Attenuates Ethanol Withdrawal Induced Hyperalgesia in Rats

Ethanol withdrawal increases sensitivity to painful stimuli. N-methyl-D-aspartate glutamate receptors may have a role in alcohol dependence and the development of withdrawal signs and symptoms. This study examined the effect of oral administration of dextromethorphan on the hyperalgesia induced by ethanol withdrawal, using hot plate assay and chemical induced writhing in rats. Wistar albino rats (250-300 g) were divided into three groups of six animals each. All the groups received 7.5% v/v alcohol and food ad libitum, for 10 days and were given saline (10 mL kg(-1)) or dextromethorphan dissolved in saline (32 and 64 mg kg(-1)) orally once daily for 10 days. Ethanol was withdrawn on day 10. The reaction times on the hot plate were measured on Day 0, at 6, 12 h after ethanol withdrawal. The ethanol withdrawal signs were rated immediately before testing. Chemical assay using acetic acid (1% v/v) was done on day 0 and at 12 h after ethanol withdrawal. Chronic exposure to ethanol produced antinociception while withdrawal produced hyperalgesia. Repeated administration of dextromethorphan prevented ethanol withdrawal induced hyperalgesia and significantly reduced total ethanol withdrawal scores at both the doses tested. This study demonstrated that dextromethorphan can attenuate hyperalgesia during ethanol withdrawal and suggests the role of N-methyl-D-aspartate receptors in ethanol withdrawal induced hyperalgesia.