title: mGlu5 receptor and protein kinase C implicated in the development and induction of neuropathic pain following chronic ethanol consumption.
abstract: The central mechanisms of neuropathic pain following chronic ethanol consumption are poorly understood. We previously reported that the levels of metabotropic glutamate 5 (mGlu5) receptor and phosphorylated-protein kinase C (PKC) were significantly increased in the spinal cord following chronic ethanol consumption. The aim of this study was to investigate whether mGlu5 receptor and PKC inhibitors directly attenuate the neuropathic pain-like state induced by chronic ethanol treatment in rats. A significant decrease in the mechanical nociceptive threshold was observed 5 weeks of chronic ethanol consumption. This hyperalgesia was significantly attenuated by repeated i.p. injection of (S)-2,6-diamino-N-[[1-(oxotridecyl)-2-piperidinyl]methyl] hexanamide dihydrochloride (NPC15437), a selective PKC inhibitor, once a day for a week after 4 weeks of ethanol treatment. Furthermore, this hyperalgesia was also significantly attenuated by repeated i.p. injection of 6-methyl-2-[phenylethynyl]-pyridine (MPEP), a selective mGlu5 receptor inhibitor, once a day for a week after 4 weeks of ethanol treatment. Furthermore, the hyperalgesia that developed after 5 weeks of ethanol treatment was significantly suppressed by a single i.p. post-injection with either NPC15437 or MPEP. These findings constitute direct evidence that spinal mGlu5 receptor and PKC play substantial roles in the development and maintenance of an ethanol-dependent neuropathic pain-like state in rats.
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Kan
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Miwa
authors.initials: M
authors.lastname: Takatsu
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D020269:Alcoholic Neuropathy / Q000139:chemically induced / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D000431:Ethanol / Q000009:adverse effects*; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D009437:Neuralgia / Q000139:chemically induced / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects / Q000503:physiopathology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D000431:Ethanol; D011493:Protein Kinase C