title: Repeated administration of mirtazapine inhibits development of hyperalgesia/allodynia and activation of NF-kappaB in a rat model of neuropathic pain.
abstract: Antidepressants have been widely used to treat neuropathic pain for many years. However, the mechanisms of their analgesic actions are little known and remain controvertible. Recent studies indicate that cytokines in central nervous system (CNS) play a critical role in the pathological states of pain. The present study was designed to explore the effects and most appropriate dosage of mirtazapine in treating neuropathic pain and its possible neuroimmune mechanisms. L5 spinal nerve transection was done to produce hyperalgesia in rats. Mirtazapine (10, 20 and 30 mg/kg, respectively) was orally administered daily for 14 days, beginning from the 5th day after nerve transection. Mechanical and thermal hyperalgesia was measured using Von-Frey filament and Hargreaves tests before and after the surgery. Rats were then sacrificed on days 3, 7, 14, 21 post-administration. The inflammatory cytokines production such as TNFalpha, IL-1beta, IL-10 and nuclear factor kappa B (NF-kappaB) activity in brain was quantified using enzyme-linked immunosorbent assay (ELISA) and electrophoretic mobility shift assay (EMSA). We found that mirtazapine (20 and 30 mg/kg) can markedly attenuate mechanical and thermal hyperalgesia produced by nerve transection, most significantly on the 14th day. The elevated TNFalpha, IL-1beta and NF-kappaB in brain were accordingly reduced, while the expression of increased IL-10 were even stimulated after repeated mirtazapine administration. Our data could conclude that mirtazapine suppressed neuropathic pain partially through inhibiting cerebral proinflammatory cytokines production and NF-kappaB activation in CNS.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, Jiangsu 210002, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhu
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wei
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Feng
authors.forename: Juan
authors.initials: J
authors.lastname: Song
authors.forename: Yimin
authors.initials: Y
authors.lastname: Hu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D003714:Denervation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004334:Drug Administration Schedule; D006930:Hyperalgesia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078785:Mirtazapine; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000293:injuries / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000929:Antidepressive Agents, Tricyclic; D016207:Cytokines; D053583:Interleukin-1beta; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008803:Mianserin; D000078785:Mirtazapine