The effect of intrathecal administration of the 5-HT 3 receptor agonist 2-methyl-5-hydroxytryptamine (2m-5HT) on jaw muscle activity evoked by mustard oil (MO) injection into the temporomandibular joint of anesthetized rats was examined. One microgram or 100 μg of 2m-5HT significantly enhanced or suppressed jaw muscle responses, respectively. Pre-administration of tropisetron, a 5-HT 3 receptor antagonist, attenuated the effect of 2m-5HT. These results indicate that activation of 5-HT 3 receptors can modulate trigeminal nociceptive responses.