title: The role of spinal serotonin receptor and alpha adrenoceptor on the antiallodynic effects induced by intrathecal milnacipran in chronic constriction injury rats.
abstract: Milnacipran, a reuptake inhibitor of noradrenaline (NA) and serotonin (5-HT), elicits an antiallodynic effect in rats with neuropathic pain; however, the role of NA and 5-HT receptors in the induction of the antiallodynic effect of milnacipran remains unclear. Thus, we examined the effects of prazosin as an α1 adrenoceptor antagonist, yohimbine as an α2 adrenoceptor antagonist, metergoline as a 5-HT1, 5-HT2 and 5-HT7 receptor antagonist, cyanopindolol as a 5-HT1A/1B receptor antagonist, ketanserin as a 5-HT2 receptor antagonist, and ondansetoron as a 5-HT3 receptor antagonist on the antiallodynic effect of milnacipran in neuropathic rats with chronic constriction injury (CCI). The CCI rats expressed mechanical and thermal allodynia, which was attenuated by intrathecal injection of milnacipran. Yohimbine, but not prazosin, reversed the milnacipran-induced antiallodynic effect. The antiallodynic effect of milnacipran was also reversed by metergoline, ketanserin and ondansetron, while cyanopindolol reversed the antiallodynic effect on mechanical, but not thermal stimulation. Furthermore, c-Fos expression in lamina I/II of the spinal dorsal horn was enhanced by thermal stimulation and the enhanced expression of c-Fos was suppressed by milnacipran. This effect of milnacipran was reversed by yohimbine, metergoline, katanserin and ondansetron, but not prazosin. These results indicate that the effect of milnacipran on mechanical and thermal allodynia and c-Fos expression is elicited through the α2 adrenoceptor, but not α1 adrenoceptor, and 5-HT2 and 5-HT3 receptors; furthermore, the 5-HT1A/1B receptor is involved in mechanical allodynia, but not thermal allodynia.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Division of Neurobiology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Takeda
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Igawa
authors.affiliation: Division of Neurobiology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Rumi
authors.initials: R
authors.lastname: Naono-Nakayama
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Sakoda
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nishimori
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan. Electronic address: ishiday@med.miyazaki-u.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishida
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003250:Constriction; D003521:Cyclopropanes / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D055595:Mechanical Phenomena; D000078764:Milnacipran; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D013116:Spinal Cord / Q000378:metabolism*; D013696:Temperature
chemical_list: D000317:Adrenergic alpha-Antagonists; D003521:Cyclopropanes; D016760:Proto-Oncogene Proteins c-fos; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D000078764:Milnacipran
keywords: Adrenoceptor; Mechanical allodynia; Milnacipran; Serotonin receptor; Thermal allodynia