Involvement of 5-hydroxytryptamine 1A receptors in the descending anti-nociceptive pathway from periaqueductal gray to the spinal dorsal horn in intact rats, rats with nerve injury and rats with inflammation

Abstract

Studies have shown that 5-hydroxytryptamine (5-HT) plays an important role in the descending pathway of pain modulation from brainstem to the spinal cord. Using selective 5-HT receptor antagonists, the present study investigated which type of 5-HT receptor(s) in the spinal cord was involved in the morphine-induced anti-nociception in intact rats, in rats with nerve injury and in rats with inflammation. The hindpaw withdrawal latencies decreased significantly after sciatic nerve injury and hindpaw inflammation compared with intact rats. Intrathecal administration of 25 or 10 μg of the selective 5-HT 1A recepter antagonist spiroxatrine, but not 1 μg of spiroxatrine, significantly blocked the increased hindpaw withdrawal latencies to thermal and mechanical stimulation induced by intra-periaqueductal gray injection of 1 μg of morphine in intact rats. Intrathecal injection of the 5-HT 2 receptor antagonist RS 102221 and the 5-HT 3 receptor antagonist MDL 72222 had no significant effects on the increased hindpaw withdrawal latencies to both noxious stimulations induced by intra-periaqueductal gray injection of morphine. Furthermore, intrathecal administration of spiroxatrine, but not RS 102221 nor MDL 72222, significantly attenuated the increased hindpaw withdrawal latencies induced by intra-periaqueductal gray administration of morphine in rats with nerve injury and in rats with inflammation. The results demonstrate that the 5-HT 1A receptor, not 5-HT 2 nor 5-HT 3 receptor, plays an important role in the descending pathway of anti-nociception from the brainstem to the spinal cord in intact rats, in rats with nerve injury and in rats with inflammation.