title: BDNF/TRK/KCC2 pathway in nicotine withdrawal-induced hyperalgesia.
abstract: OBJECTIVE
  To investigate the effect of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase (Trk) on potassium chloride cotransporter 2 (KCC2) in rats following nicotine withdrawal and the roles played by BDNF/Trk/KCC2 pathway in nicotine withdrawal-induced hyperalgesia.
  
  
  METHODS
  Seventy-eight rats were randomly assigned to five groups: control group (n = 12) without any treatment, normal saline group (NS group, n = 12) and nicotine withdrawal group (NW group, n = 30) receiving a subcutaneous injection of saline or nicotine for 7 days, respectively. The NW + dimethyl sulfoxide (DMSO) (n = 12) and NW+ Trk antagonist K252a groups (n = 12) received an intrathecal injection of DMSO (10 μl) and K252a (10 μg/10 μl) for 3 days after nicotine withdrawal, respectively. Nicotine withdrawal was precipitated by subcutaneous injection of nonselective and noncompetitive antagonist of nicotinic acetylcholine receptors mecamylamine. Pain was tested using thermal withdrawal latency (TWL). A Western blot was used to examine the expression of BDNF and KCC2.
  
  
  RESULTS
  The TWL was significantly decreased in NW group relative to control and NS groups (P< 0.01). Compared with the NW group, the NW+K252a group manifested a significantly higher latency (P< 0.01). The BDNF expression was increased and KCC2 was decreased in NW group compared with the control group (P< 0.01). K252a reduced KCC2 downregulation.
  
  
  CONCLUSIONS
  BDNF/Trk signaling may contribute to nicotine withdrawal-induced hyperalgesia via downregulation of KCC2.
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology & Jiangsu Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, Jiangsu 221000, P. R. China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Shi
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology & Jiangsu Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, Jiangsu 221000, P. R. China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Anesthesiology, Laocheng People's Hospital, Liaocheng, Shandong 252000, P. R. China.
authors.forename: Ailan
authors.initials: A
authors.lastname: Yu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology & Jiangsu Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, Jiangsu 221000, P. R. China.
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology & Jiangsu Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, Jiangsu 221000, P. R. China; Department of Anesthesiology, Laocheng People's Hospital, Liaocheng, Shandong 252000, P. R. China.
authors.forename: Zongwang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology & Jiangsu Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, Jiangsu 221000, P. R. China.
authors.forename: Li-Cai
authors.initials: LC
authors.lastname: Zhang
keywords: Brain-derived neurotrophic factor (BDNF); Nicotine withdrawal; Potassium chloride cotransporter 2 (KCC2)