PMID- 30570747 OWN - NLM STAT- MEDLINE DCOM- 20200313 LR - 20200313 IS - 1471-4159 (Electronic) IS - 0022-3042 (Linking) VI - 149 IP - 6 DP - 2019 Jun TI - Rostral ventromedial medulla-mediated descending facilitation following P2X7 receptor activation is involved in the development of chronic post-operative pain. PG - 760-780 LID - 10.1111/jnc.14650 [doi] AB - Chronic postsurgical pain (CPSP) remains a medical problem. Whether the descending modulation of nociceptive transmission from the rostral ventromedial medulla (RVM) plays a role in CPSP induced by skin/muscle incision and retraction (SMIR) in the thigh is still unknown. In this study, we found that SMIR surgery, which induced either bilateral or unilateral mechanical allodynia, activated microglia, and up-regulated interleukin-1beta (IL-1beta), an important cytokine, and 8-hydroxyguanine, an oxidative stress marker in the RVM. In addition, the release of 5-hydroxytryptamine (5-HT) was increased in the ipsilateral and contralateral RVM in rats with either bilateral or unilateral pain following SMIR. The 5-HT level increase, 5-HT3 receptor (5-HT3R) up-regulation, and microglia activation were found bilaterally in SMIR rats with bilateral pain, but only ipsilaterally in SMIR rats with unilateral pain. The intrathecal injection of the 5-HT3R antagonist Y25130 prevented the development of CPSP and the activation of spinal microglia induced by SMIR. Furthermore, P2X7 receptor (P2X7R) was up-regulated in microglia in the RVM. The microinjection of the P2X7R antagonist brilliant blue G (BBG, a non-competitive P2X7R antagonist) into the RVM prevented the development of mechanical allodynia, inhibited the activation of microglia, and decreased the expression of IL-1beta and 8-hydroxyguanine in the RVM following SMIR. Importantly, BBG injected into the RVM also decreased the activation of microglia and the level of 5-HT in the lumbar 3 (L3) spinal cord. The microinjection of the P2X7R agonist BzATP, the NADPH oxidase activator phorbol-12-myristate-13-acetate, or IL-1beta into the RVM induced bilateral mechanical allodynia, microglia activation, and 5-HT release in the L3 spinal dorsal horn. Taken together, P2X7R activation in microglia in the RVM following SMIR might be responsible for the development of CPSP via activating descending serotonergic pathway. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. CI - (c) 2018 International Society for Neurochemistry. FAU - Wang, Wei AU - Wang W AD - Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. FAU - Zhong, Xiongxiong AU - Zhong X AD - Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. FAU - Li, Yongyong AU - Li Y AD - Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. FAU - Guo, Ruixian AU - Guo R AD - Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. AD - Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong, People's Republic of China. FAU - Du, Sujuan AU - Du S AD - Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Wen, Lili AU - Wen L AD - Department of Anesthesiology, Cancer Center, State Key Laboratory of Oncology in South China, Collaborative, Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, P. R. China. FAU - Ying, Yanlu AU - Ying Y AD - Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - Yang, Tao AU - Yang T AD - Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Wei, Xu-Hong AU - Wei XH AUID- ORCID: 0000-0002-9722-3694 AD - Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. AD - Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190131 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Receptors, Purinergic P2X7) SB - IM MH - Animals MH - Chronic Pain/metabolism MH - Hyperalgesia/metabolism MH - Male MH - Medulla Oblongata/*metabolism MH - Microglia/*metabolism MH - Neural Pathways/*metabolism MH - Pain, Postoperative/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Purinergic P2X7/*metabolism MH - Spinal Cord/metabolism OTO - NOTNLM OT - 5-hydroxytryptamine OT - Interleukin-1beta OT - P2X7 receptors OT - chronic post-operative pain OT - microglia OT - rostral ventromedial medulla EDAT- 2018/12/21 06:00 MHDA- 2020/03/14 06:00 CRDT- 2018/12/21 06:00 PHST- 2018/06/28 00:00 [received] PHST- 2018/10/14 00:00 [revised] PHST- 2018/12/12 00:00 [revised] PHST- 2018/12/12 00:00 [accepted] PHST- 2018/12/21 06:00 [pubmed] PHST- 2020/03/14 06:00 [medline] PHST- 2018/12/21 06:00 [entrez] AID - 10.1111/jnc.14650 [doi] PST - ppublish SO - J Neurochem. 2019 Jun;149(6):760-780. doi: 10.1111/jnc.14650. Epub 2019 Jan 31.