title: Antinociceptive effects of venlafaxine in a rat model of peripheral neuropathy: role of alpha2-adrenergic receptors.
abstract: This study was designed to determine whether acute or chronic venlafaxine administration was effective in alleviating symptoms of neuropathic pain in a rat model of neuropathic pain, and whether the effect of venlafaxine involved manipulation of α2-adrenoceptors,by determining the effect of yohimbine, a α2-adrenoceptor antagonist on its actions. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in the rats that resulted in stimulus-evoked thermal hyperalgesia, tactile mechanical and cold allodynia. Acute venlafaxine injections (20 and 40 mg/kg i.p.) on the 7th, 14th and 21st postoperative days could not reduce tactile and cold hypersensitivity significantly compared to CCI group. But in these groups venlafaxine (40 mg/kg i.p.) blocked heat hyperalgesia. When venlafaxine (10 and 20mg/kg i.p.) administration was started on the first day after CCI and given daily until the 14th day, tactile hypersensitivity and heat hyperalgesia considerably were attenuated. But when venlafaxine (20mg/kg i.p.) treatment was initiated on the 10th day after CCI, once the model had been fully established, and given daily for 11 days, no differences in withdrawal thresholds were observed compared with CCI group however heat hyperalgesia significantly has been blocked. Also the effect of venlafaxine on heat hyperalgesia was reversed by pretreatment with yohimbine at all-time intervals. These results indicate that venlafaxine, when administered immediately after nerve injury, and for a sufficient period of time, can prevent the development and expression of neuropathic pain. Also we conclude that α2-adrenoceptors participate in the antinociceptive effects of venlafaxine.
authors.affiliation: Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Valiollah
authors.initials: V
authors.lastname: Hajhashemi
authors.affiliation: Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran; Department of Addiction Studies, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Banafshe
authors.affiliation: Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Minaiyan
authors.affiliation: Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran.
authors.forename: Azam
authors.initials: A
authors.lastname: Mesdaghinia
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: alirezaabed@pharm.mui.ac.ir.
authors.forename: Alireza
authors.initials: A
authors.lastname: Abed
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003511:Cyclohexanols / Q000494:pharmacology* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D000069470:Venlafaxine Hydrochloride; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics; D003511:Cyclohexanols; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D000069470:Venlafaxine Hydrochloride
keywords: Chronic constriction injury; Neuropathic pain; Venlafaxine; Yohimbine