title: Mechanical Antiallodynic Effect of Intrathecal Nefopam in a Rat Neuropathic Pain Model.
abstract: Nefopam has a pharmacologic profile distinct from that of opioids or other anti-inflammatory drugs. Several recent studies demonstrate that nefopam has a mechanism of action similar to those of anti-depressants and anticonvulsants for treating neuropathic pain. The present study investigates the mechanical antiallodynic effect of nefopam using immunohistochemical study and western blot analysis in a rat neuropathic pain model. Twenty-eight male Sprague-Dawley rats were subjected to left fifth lumbar (L5) spinal nerve ligation and intrathecal catheter implantation, procedures which were not performed on the 7 male Sprague-Dawley rats in the sham surgery group (group S). Nefopam, either 10 or 100 µg/kg (group N10 or N100, respectively), and normal saline (group C) were intrathecally administered into the catheter every day for 14 days. The mechanical allodynic threshold of intrathecal nefopam was measured using a dynamic plantar aesthesiometer. Immunohistochemistry targeting cluster of differentiation molecule 11b (CD11b) and glial fibrillary acidic protein (GFAP) was performed on the harvested spinal cord at the level of L5. Extracellular signal-regulated kinase 1/2 (ERK 1/2) and cyclic adenosine monophosphate response element binding protein (CREB) were measured using western blot analysis. The N10 and N100 groups showed improved mechanical allodynic threshold, reduced CD11b and GFAP expression, and attenuated ERK 1/2 and CREB in the affected L5 spinal cord. In conclusion, intrathecal nefopam reduced mechanical allodynia in a rat neuropathic pain model. Its mechanical antiallodynic effect is associated with inhibition of glial activation and suppression of the transcription factors' mitogen-activated protein kinases in the spinal cord.
authors.affiliation: Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine; Research Institute for Convergence of biomedical science and technology Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Kyung-Hoon
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine; Research Institute for Convergence of biomedical science and technology Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Gyeong-Jo
authors.initials: GJ
authors.lastname: Byeon
authors.affiliation: Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine; Research Institute for Convergence of biomedical science and technology Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine; Research Institute for Convergence of biomedical science and technology Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Baek
authors.affiliation: Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine; Research Institute for Convergence of biomedical science and technology Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Shin
authors.affiliation: Division of Meridian and Structural Medicine, Pusan National University School of Korean Medicine, Yangsan, Korea.
authors.forename: Sung-Tae
authors.initials: ST
authors.lastname: Koo
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D009340:Nefopam / Q000008:administration & dosage*; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D058748:Pain Perception / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D009340:Nefopam
keywords: Mechanical Allodynia; Nefopam; Neuropathic Pain; Spinal Nerve Ligation