Oral and spinal melatonin reduces tactile allodynia in rats via activation of MT 2 and opioid receptors

Abstract

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 μg) 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 μg), but not vehicle, significantly diminished in a dose-dependent manner the antiallodynic effect induced by melatonin (100 μg, it). Oral (0.01–1 mg/kg) or intrathecal (0.1–10 μg) administration of the highly selective MT 2 receptor antagonist 4P-PDOT diminished the antiallodynic activity induced by oral (150 mg/kg) or intrathecal (100 μg) administration of melatonin, respectively. Subcutaneous (1 mg/kg) or intrathecal (0.5–50 μg) treatment with naltrexone, but not vehicle, significantly diminished the antiallodynic effect induced by oral (150 mg/kg) or intrathecal (100 μg) administration of melatonin. Oral melatonin (150 mg/kg)-induced antiallodynia was partially reduced by the spinal administration of 4P-PDOT (10 μg). Moreover, the spinal effect of melatonin (100 μg) was significantly reduced by the combination 4P-PDOT (0.1 μg)-naltrexone (0.5 μg). At the greatest tested doses, the antagonist drugs did not modify tactile allodynia in neuropathic rats. Melatonin (100 μg 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.