title: Antihyperalgesic, but not antiallodynic, effect of melatonin in nerve-injured neuropathic mice: Possible involvements of the L-arginine-NO pathway and opioid system.
abstract: The present study was undertaken to determine the effects of intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) melatonin on mechanical allodynia and thermal hyperalgesia in mice with partial tight ligation of the sciatic nerve, and how the nitric oxide (NO) precursor l-arginine and the opiate antagonist naloxone influence this effect. A plantar analgesic meter was used to assess thermal hyperalgesia, and nerve injury-induced mechanical hyperalgesia was assessed with von Frey filaments. 1-5 weeks following the surgery, marked mechanical allodynia and thermal hyperalgesia developed in neuropathic mice. Intracerebroventricular and intraperitoneal melatonin, with its higher doses, produced a blockade of thermal hyperalgesia, but not mechanical allodynia. Administration of both l-arginine and naloxone, at doses which produced no effect on their own, partially reversed antihyperalgesic effect of melatonin. These results suggest that although it has different effects on neuropathic pain-related behaviors, melatonin may have clinical utility in neuropathic pain therapy in the future. It is also concluded that l-arginine-NO pathway and opioidergic system are involved in the antihyperalgesic effect of melatonin in nerve-injured mice.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey. aulugol@trakya.edu.tr
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ulugol
authors.forename: Dikmen
authors.initials: D
authors.lastname: Dokmeci
authors.forename: Gurkan
authors.initials: G
authors.lastname: Guray
authors.forename: Nese
authors.initials: N
authors.lastname: Sapolyo
authors.forename: Filiz
authors.initials: F
authors.lastname: Ozyigit
authors.forename: Melek
authors.initials: M
authors.lastname: Tamer
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000502:physiology*; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008550:Melatonin / Q000008:administration & dosage*; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage; D009569:Nitric Oxide / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries; D020426:Sciatic Neuropathy / Q000188:drug therapy
chemical_list: D000700:Analgesics; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009569:Nitric Oxide; D009270:Naloxone; D001120:Arginine; D008550:Melatonin