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Salivary melatonin response to acute pain stimuli

Evidence for a relationship between melatonin, nociception, and analgesia in humans is based on data that are only linked by association and simultaneous occurrence. Studies have reported inverse correlation of the circadian melatonin rhythm with nociception latency and enhancement of opioid analgesia by simultaneous administration of melatonin in animals. This study examines the response of salivary melatonin to acute pain stimuli in 18 healthy subjects ranging in age from 19 to 50 years. A biphasic melatonin response following an acute pain stimulus of 36 V was observed, F(8, 8)=17.839, P<0.001. Within 5 min of the stimulus, melatonin decreased and reached a plateau of 36 pg/mL below baseline by 20 min. This decrease was followed by an increase of 5 pg/mL. Melatonin levels subsequently decreased until they had reached levels similar to those anticipated for the time of day and did not vary thereafter. The magnitude of the melatonin response was not related to age or gender. There was no association between voltage and magnitude of the melatonin responses observed at 15 min (r=0.185, P=0.51) or at 30 min (r=0.468, P=0.09). This study provides the first evidence of melatonin utilization and subsequent pineal gland synthesis following acute pain episodes in humans.