Oral and spinal melatonin reduces tactile allodynia in rats via activation of MT2 and opioid receptors.

The antiallodynic effect of melatonin after intrathecal (it) and oral administration as well as the possible participation of MT(2) and opioid receptors in melatonin-induced antiallodynia in neuropathic rats were assessed. Ligation of the L5/L6 spinal nerves produced a clear-cut tactile allodynia in the rats. Intrathecal (3-100 microg) and oral (37.5-300 mg/kg) administration of melatonin decreased tactile allodynia induced by spinal nerve ligation. Intrathecal administration of the preferential MT(2) receptor antagonist luzindole (1-100 microg), but not vehicle, significantly diminished in a dose-dependent manner the antiallodynic effect induced by melatonin (100 microg, it). Oral (0.01-1mg/kg) or intrathecal (0.1-10 microg) administration of the highly selective MT(2) receptor antagonist 4P-PDOT diminished the antiallodynic activity induced by oral (150 mg/kg) or intrathecal (100 microg) administration of melatonin, respectively. Subcutaneous (1mg/kg) or intrathecal (0.5-50 microg) treatment with naltrexone, but not vehicle, significantly diminished the antiallodynic effect induced by oral (150 mg/kg) or intrathecal (100 microg) administration of melatonin. Oral melatonin (150 mg/kg)-induced antiallodynia was partially reduced by the spinal administration of 4P-PDOT (10 microg). Moreover, the spinal effect of melatonin (100 microg) was significantly reduced by the combination 4P-PDOT (0.1 microg)-naltrexone (0.5 microg). At the greatest tested doses, the antagonist drugs did not modify tactile allodynia in neuropathic rats. Melatonin (100 microg or 300 mg/kg) did not affect motor co-ordination in the rotarod test. Results indicate that melatonin reduces tactile allodynia in neuropathic rats after intrathecal and oral administration. Moreover, data suggest the participation of spinal MT(2) and opioid receptors in the melatonin-induced antiallodynic effect in this model.