The molecular mechanisms of the analgesic action of melatonin

Objective To analyse the potential involvement of the opioid receptor gene expression in the mechanisms of the analgesic action of melatonin.Methods A trauma-pain model was established in Wistar rats by combining right-hind limb amputation with 50 ℃ tail-flick test.Antinociception was determined by tail-flick latency to hot waster at 50 ℃.RT-PCR was used to observe the the expression of the M1OR and KOR gene.Results Melatonin produced the antinociceptive effect in dose-dependent manner after i.p or i.c.v.administration.Injected i.c.v.to rats,naloxone(10 μg)obviously antagonized the antinociceptive effect induced by i.p.melatonin.The expression of the M1OR gene in the rat hypothalamus and the KOR gene in the hippocampus was both significantly reduced at day 3 after injury,which was parallel to the reduction of the rat pain thresholds.However,the expression of the M1OR gene in the hippocampus and the KOR gene in the hypothalamus was not changed.Treatment of trauma-pain rats with melatonin(30-120 mg·kg-1)i.p.administrated induced the up-regulation of M1OR mRNA in the hypothalamus and the KOR mRNA in the hippocampus in a concentration-dependent manner.Conclusions The present observations suggest that Melatonin-induced antinociceptive effect may partially contribute to the up-regulation of M1OR mRNA level in the hypothalamus and the KOR mRNA level in the hippocampus.