title: Role of the 5-HT(7) receptor in the effects of intrathecal nefopam in neuropathic pain in rats.
abstract: Nefopam is a non-opioid analgesic drug, used widely in European countries to control postoperative pain. However, its mechanism of action remains unclear. In this study, the effects of intrathecal nefopam on spinal nerve-ligated induced neuropathic pain in rats were examined and the involvement of the 5-HT7 receptor at the spinal level was determined. Next, a 5-HT7 receptor antagonist (SB-269970) or descending serotonergic pathway ablation agent (5,7-DHT) was administered intrathecally before delivery of the nefopam to determine the contribution of spinal 5-HT7 receptors or descending serotonergic pathway to the activity of nefopam. The concentrations of 5-HT were measured. Intrathecal nefopam dose-dependently produced the antiallodynic effect. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect of the nefopam. 5,7-DHT failed to affect the effect of nefopam. The concentrations of 5-HT in the spinal cord and plasma were decreased in neuropathic pain. Intrathecal nefopam increased the levels of 5-HT in the spinal cord and plasma. Intrathecal nefopam is effective in the attenuation of neuropathic pain induced by spinal nerve ligation and nefopam increases the level of 5-HT. Additionally, the 5-HT7 receptor is involved in the antiallodynic action of nefopam in the spinal cord.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Republic of Korea.
authors.forename: Lee Jae
authors.initials: LJ
authors.lastname: Dam
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Republic of Korea; Center for Creative Biomedical Scientists at Chonnam National University, Gwangju, Republic of Korea. Electronic address: mhyoon@chonnam.ac.kr.
authors.forename: Lin
authors.initials: L
authors.lastname: Hai
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Republic of Korea; Center for Creative Biomedical Scientists at Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Yoon Myung
authors.initials: YM
authors.lastname: Ha
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D009340:Nefopam / Q000494:pharmacology* / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D010636:Phenols / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000378:metabolism; D013127:Spinal Nerves / Q000293:injuries; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D018712:Analgesics, Non-Narcotic; D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D012701:Serotonin; D009340:Nefopam
keywords: 5-HT concentration; 5-HT(7) receptor; Antiallodynia; Nefopam; Neuropathic pain; Spinal cord