title: Blocking TNF-α with infliximab alleviates ovariectomy induced mechanical and thermal hyperalgesia in rats.
abstract: Studies have proved an increased expression of tumor necrosis factor alpha (TNF-α) in estrogen deficiency animals, and TNF-α also plays a role in inflammation and neuropathic pain. This study aimed to explore the relationship between TNF-α and ovariectomy induced hyperalgesia. 36 female Sparague-Dawley were included, estrogen depletion models were established by ovariectomy. Then infliximab (a TNF-α blocker) was administrated to the ovariectomized rats for 8 weeks. Pain behavioral tests were performed once a week. The bone mineral density (BMD), serum estradiol and TNF-α level were determined at the 8th week after ovariectomy. The expression of TNF-α in lumbar 5 dorsal root ganglions (L5 DRGs) was examined by immunofluorescence method. Significant hyperalgesia to mechanical and thermal stimuli in groups Ovx-1 and Ovx-2 was observed 1 week after the operation. After treated with infliximab, the pain threshold of Ovx-2 was partially restored, although still lower than the Sham group. The serum TNF-α level of Ovx-1 was significantly higher than Sham and Ovx-2. TNF-α immunofluorescence indicated a significant increase in the expression of TNF-α at L5 DRGs in group Ovx-1 when compared with groups Sham and Ovx-2. The BMD of group Ovx-2 was significantly higher than group Ovx-1 and lower than group Sham. In conclusion, TNF-α plays an important role in estrogen deficiency induced mechanical and thermal hyperalgesia, and DRG may be one site on which TNF-α acts to cause hyperalgesia. Blocking the effect of TNF-α could partially alleviate the estrogen deficiency induced hyperalgesia in rats. Thus, TNF-α may contribute to chronic pain in postmenopausal women.
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan second Road, Guangzhou, 510080, China. berlinch2007@yahoo.com.cn
authors.forename: Bai Ling
authors.initials: BL
authors.lastname: Chen
authors.forename: Yi Qiang
authors.initials: YQ
authors.lastname: Li
authors.forename: Deng Hui
authors.initials: DH
authors.lastname: Xie
authors.forename: Qiu Lan
authors.initials: QL
authors.lastname: He
authors.forename: Xiao Xi
authors.initials: XX
authors.lastname: Yang
mesh_terms: D015502:Absorptiometry, Photon; D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D000069285:Infliximab; D010052:Ovariectomy / Q000009:adverse effects*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D000069285:Infliximab