BDNF/Trk/KCC2 pathway in nicotine withdrawal-induced hyperalgesia

• Published in: Translational neuroscience Vol. 6; no. 1; pp. 208 - 213
• Main Authors: Shi, Wenhui, Ding, Yonghong, Yu, Ailan, Wang, Qinghe, Zhang, Zongwang, Zhang, Li-Cai
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter Open 01.01.2015; De Gruyter Poland; De Gruyter
• Subjects: Acetylcholine receptors (nicotinic); Brain-derived neurotrophic factor; Brain-derived neurotrophic factor (BDNF); Dimethyl sulfoxide; Hyperalgesia; Injection; Kinases; Latency; Mecamylamine; Nicotine; Nicotine withdrawal; Pain perception; Potassium chloride; Potassium chloride cotransporter 2 (KCC2); Potassium-chloride cotransporter; Receptors; Tobacco smoke; Tropomyosin; Brain-derived neurotrophic factor (BDNF); Potassium chloride cotransporter 2 (KCC2); Nicotine withdrawal
• ISSN: 2081-3856; 2081-6936; 2081-6936
• DOI: 10.1515/tnsci-2015-0022

Purpose: 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. Conclusion: BDNF/Trk signaling may contribute to nicotine withdrawal-induced hyperalgesia via downregulation of KCC2.