5-hydroxytryptamine 1A (5-HT1A) but not 5-HT3 receptor is involved in mediating the nucleus submedius 5-HT-evoked antinociception in the rat

Our previous studies have indicated that the thalamic nucleus submedius (Sm) is involved in modulation of nociception as part of an ascending component of an endogenous analgesic system consisting of spinal cord-Sm-ventrolateral orbital cortex (VLO)-periaqueductal gray (PAG)-spinal cord loop. Microinjection of 5-hydroxytryptamine (5-HT) into Sm produces antinociception and this effect is blocked by 5-HT2 receptor antagonist. The aim of the present study was to examine whether the 5-HT1 and 5-HT3 receptors were also involved in the Sm 5-HT-evoked antinociception. Nociception was assessed in lightly anesthetized rats with radiant-heat-evoked tail flick (TF). 5-HT1A and 5-HT3 receptor antagonists were microinjected into the Sm alone or in combination with a microinjection of 5-HT into the same Sm site. 5-HT1A receptor antagonist p-MPPI (0.87 nmol) facilitated the TF reflex; a lower dose (0.43 nmol) of p-MPPI significantly attenuated the Sm 5-HT-evoked inhibition of TF reflex. Microinjection of the 5-HT3 receptor antagonist LY-278,584 (12 nmol) had no effect either on the TF reflex or on the Sm 5-HT-evoked inhibition. These results suggest that 5-HT1A receptor but not 5-HT3 receptor is involved in mediating the 5-HT-evoked antinociception. Possible mechanisms of Sm 5-HT-induced descending antinociception are discussed.