title: Exogenous melatonin abolishes mechanical allodynia but not thermal hyperalgesia in neuropathic pain. The role of the opioid system and benzodiazepine-gabaergic mechanism.
abstract: Melatonin (MT) is a neurohormone synthesized and secreted by the pineal gland. MT plays an important role in the regulation of physiological and neuroendocrine functions. The purpose of this study was to assess the overall effect of melatonin on neuropathic pain, the type of melatonin receptor involved, and potential role of the opioid system and GABA(A) receptors. The experiments were conducted by using the animal neuropathic pain model (CCI). The rats with CCI showed the characteristic for the mechanical allodynia and thermal hyperalgesia signs that were calculated by using the von Frey's and Hargreaves' tests. The conducted studies measured the effects of intraperitoneal administration of naloxone (opioid antagonist), prazosin (MT3 antagonist), luzindole (MT1/MT2 receptor antagonist), picrotoxin (GABA(A) antagonist) and flumazenil (benzodiazepine antagonist) on the antinociceptive effects caused by melatonin. Melatonin caused the increase in the pain threshold of the mechanical allodynia and the slight increase in the threshold of the thermal hyperalgesia. The pre-treatment with naloxone completely abolished the antinociceptive effects of melatonin in von Frey's test, but not thermal sensation in the Hargreaves's test. Prazosin did not have any effects, while administration of luzindole significantly suppressed the antinociceptive effect of melatonin. The antiallodynic effect of MT was also abolished by flumazenil and picrotoxin. Melatonin influences the mechanical allodynia but not thermal hyperalgesia via activation of opioid system and benzodiazepine-GABAergic pathway. Antinociceptive effects of melatonin are mostly related to the MT1/MT2 receptors interaction.
authors: Department of Pathophysiology, Jagiellonian University Medical College, Cracow, Poland. danski@mp.pl
authors: D
authors: D
authors: Zurowski
authors: L
authors: L
authors: Nowak
authors: A
authors: A
authors: Machowska
authors: J
authors: J
authors: Wordliczek
authors: P J
authors: PJ
authors: Thor
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement; D058748:Pain Perception / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D044094:Receptors, Melatonin / Q000187:drug effects / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012585:Sciatica / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000700:Analgesics; D002352:Carrier Proteins; D058787:GABA-A Receptor Antagonists; D009292:Narcotic Antagonists; D011963:Receptors, GABA-A; D044094:Receptors, Melatonin; D011957:Receptors, Opioid; C069997:Tspo protein, rat; D008550:Melatonin