PMID- 29872336 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220317 IS - 1178-7090 (Print) IS - 1178-7090 (Electronic) IS - 1178-7090 (Linking) VI - 11 DP - 2018 TI - Dexmedetomidine attenuates persistent postsurgical pain by upregulating K(+)-Cl(-) cotransporter-2 in the spinal dorsal horn in rats. PG - 993-1004 LID - 10.2147/JPR.S158737 [doi] AB - BACKGROUND: Dexmedetomidine (DEX) could have an analgesic effect on pain transmission through the modulation of brain-derived neurotrophic factor (BDNF). In addition, KCC2-induced shift in neuronal Cl- homeostasis is crucial for postsynaptic inhibition mediated by GABAA receptors. Accumulating evidence shows that nerve injury, peripheral inflammation and stress activate the spinal BDNF/TrkB signal, which results in the downregulation of KCC2 transport and expression, eventually leads to GAGAergic disinhibition and hyperalgesia. The aim of this experiment was to explore the interaction between DEX and KCC2 at a molecular level in rats in the persistent postsurgical pain (PPSP). METHODS: PPSP in rats was evoked by the skin/muscle incision and retraction (SMIR). Mechanical hypersensitivity was assessed with the Dynamic Plantar Aesthesiometer. Western blot and immunofluorescence assay were used to assess the expressions of related proteins. RESULTS: In the first part of our experiment, the results revealed that the BDNF/TrkB-KCC2 signal plays a critical role in the development of SMIR-evoked PPSP; the second part showed that intraperitoneal administrations of 40 microg/kg DEX at 15 min presurgery and 1 to 3 days post-surgery significantly attenuated SMIR-evoked PPSP. Simultaneously, SMIR-induced KCC2 downregulation was partly reversed, which coincided with the inhibition of the BDNF/TrkB signal in the spinal dorsal horn. Moreover, intrathecal administrations of KCC2 inhibitor VU0240551 significantly reduced the analgesic effect of DEX on SMIR-evoked PPSP. CONCLUSION: The results of our study indicated that DEX attenuated PPSP by restoring KCC2 function through reducing BDNF/TrkB signal in the spinal dorsal horn in rats, which provides a new insight into the treatment of chronic pain in clinical postsurgical pain management. FAU - Dai, Shuhong AU - Dai S AD - Department of Anesthesiology, XuZhou Central Hospital, Xuzhou, China. FAU - Qi, Yu AU - Qi Y AD - Department of Anesthesiology, XuZhou Central Hospital, Xuzhou, China. FAU - Fu, Jie AU - Fu J AD - Department of Anesthesiology, XuZhou Central Hospital, Xuzhou, China. FAU - Li, Na AU - Li N AD - Department of Anesthesiology, XuZhou Central Hospital, Xuzhou, China. FAU - Zhang, Xu AU - Zhang X AD - Department of Anesthesiology, XuZhou Central Hospital, Xuzhou, China. FAU - Zhang, Juan AU - Zhang J AD - The Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China. FAU - Zhang, Wei AU - Zhang W AD - The Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China. FAU - Xu, Haijun AU - Xu H AD - Department of Anesthesiology, XuZhou Central Hospital, Xuzhou, China. FAU - Zhou, Hai AU - Zhou H AD - Department of Anesthesiology, XuZhou Central Hospital, Xuzhou, China. FAU - Ma, Zhengliang AU - Ma Z AD - The Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China. LA - eng PT - Journal Article DEP - 20180523 PL - New Zealand TA - J Pain Res JT - Journal of pain research JID - 101540514 PMC - PMC5973459 OTO - NOTNLM OT - BDNF/TrkB signal OT - KCC2 OT - dexmedetomidine OT - persistent postsurgical pain OT - skin/muscle incision and retraction COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2018/06/07 06:00 MHDA- 2018/06/07 06:01 PMCR- 2018/05/23 CRDT- 2018/06/07 06:00 PHST- 2018/06/07 06:00 [entrez] PHST- 2018/06/07 06:00 [pubmed] PHST- 2018/06/07 06:01 [medline] PHST- 2018/05/23 00:00 [pmc-release] AID - jpr-11-993 [pii] AID - 10.2147/JPR.S158737 [doi] PST - epublish SO - J Pain Res. 2018 May 23;11:993-1004. doi: 10.2147/JPR.S158737. eCollection 2018.