TY - JOUR
T1 - Melatonin
T2 - A hormone that modulates pain
AU - Ambriz-Tututi, Mónica
AU - Rocha-González, Héctor I.
AU - Cruz, Silvia L.
AU - Granados-Soto, Vinicio
N1 - Funding Information:
Authors greatly appreciate the bibliographic assistance B.Sc. Héctor Vázquez. Mónica Ambriz-Tututi and Héctor I. Rocha-González are Conacyt fellows. Partially supported by Conacyt, grants 59879 (VGS) and 43604-M (SC).
PY - 2009/4/10
Y1 - 2009/4/10
N2 - Aims: 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. Main 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. Key findings: 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 MT1 and MT2 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 GABAA receptor function and acts as a free radical scavenger. Significance: 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.
AB - Aims: 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. Main 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. Key findings: 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 MT1 and MT2 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 GABAA receptor function and acts as a free radical scavenger. Significance: 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.
KW - Antioxidant
KW - Central sensitization
KW - Inflammatory pain
KW - Melatonin
KW - Melatonin receptors
KW - Neuropathic pain
UR - http://www.scopus.com/inward/record.url?scp=62749136940&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2009.01.024
DO - 10.1016/j.lfs.2009.01.024
M3 - Artículo de revisión
C2 - 19223003
SN - 0024-3205
VL - 84
SP - 489
EP - 498
JO - Life Sciences
JF - Life Sciences
IS - 15-16
ER -