Prolonged rhythmic gum chewing suppresses nociceptive response via serotonergic descending inhibitory pathway in humans.

Serotonergic (5-HT) neurons are implicated in modulating nociceptive transmission. It is established that 5-HT neuronal activity is enhanced by rhythmic behaviors such as chewing and locomotion in animals. We thus hypothesized that 5-HT descending inhibitory pathways may be enhanced by rhythmic behavior of gum chewing in humans. To evaluate this idea, we examined nociceptive flexion reflex (NFR), while a subject chewed gum rhythmically for 20 min. NFR was elicited by electrical stimulation of the sural nerve, and the evoked potential was recorded from the biceps femoris muscle. Visual analogue scale (VAS) was also obtained. To assess 5-HT activity, we determined 5-HT levels quantitatively in platelet poor plasma (PPP) and whole blood (WB) using HPLC system. Both NFR area and VAS were significantly decreased at 5 min after the onset of chewing and these reductions persisted until cessation of chewing. There were no significant changes in NFR and VAS while resting without chewing. The PPP 5-HT level increased significantly just after cessation of chewing and had returned to the pre-chewing level by 30 min after cessation of chewing. The WB 5-HT level obtained 30 min after cessation of chewing was significantly greater than the pre-chewing level. Serotonin transporters have recently been discovered at the blood-brain barrier, suggesting that the rise in blood 5-HT may possibly reflect an increase in 5-HT level within the brain. The present results support our hypothesis that the rhythmic behavior of chewing suppresses nociceptive responses via the 5-HT descending inhibitory pathway.