Melatonin: a hormone that modulates pain.
OBJECTIVE
Melatonin is a hormone synthesized principally in the pineal gland that has been classically associated with endocrine actions. However, several lines of evidence suggest that melatonin plays a role in pain modulation. This paper reviews the available evidence on melatonin's analgesic effects in animals and human beings.


METHODS
A medline search was performed using the terms "melatonin", "inflammatory pain", "neuropathic pain", "functional pain", "rats", "mice", "human", "receptors", "opioid" and "free radicals" in combinations.


RESULTS
The antinociceptive effect of melatonin has been evaluated in diverse pain models, and several findings show that melatonin receptors modulate pain mechanisms as activation induces an antinociceptive effect at spinal and supraspinal levels under conditions of acute and inflammatory pain. More recently, melatonin induced-antinociception has been extended to neuropathic pain states. This effect agrees with the localization of melatonin receptors in thalamus, hypothalamus, dorsal horn of the spinal cord, spinal trigeminal tract, and trigeminal nucleus. The effects of melatonin result from activation of MT(1) and MT(2) melatonin receptors, which leads to reduced cyclic AMP formation and reduced nociception. In addition, melatonin is able to activate opioid receptors indirectly, to open several K(+) channels and to inhibit expression of 5-lipoxygenase and cyclooxygenase 2. This hormone also inhibits the production of pro-inflammatory cytokines, modulates GABA(A) receptor function and acts as a free radical scavenger.


CONCLUSIONS
Melatonin receptors constitute attractive targets for developing analgesic drugs, and their activation may prove to be a useful strategy to generate analgesics with a novel mechanism of action.
Ambriz-Tututi
Mónica
M
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Sede Sur, México, D.F., Mexico.
Rocha-González
Héctor I
HI
Cruz
Silvia L
SL
Granados-Soto
Vinicio
V
D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D008550:Melatonin / Q000096:biosynthesis / Q000502:physiology* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010870:Pineal Gland / Q000378:metabolism*; D044094:Receptors, Melatonin / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction
D000700:Analgesics; D044094:Receptors, Melatonin; D008550:Melatonin