Rostral ventromedial medulla-mediated descending facilitation following P2X7 receptor activation is involved in the development of chronic post-operative pain
Rostral ventromedial medulla-mediated descending facilitation following P2X7 receptor activation is involved in the development of chronic post-operative pain
复制标题
P2X7 受体激活后延髓头侧腹内侧介导的下降促进参与慢性术后疼痛的发生
DOI：
10.1111/jnc.14650
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发表时间：
2019
影响因子：
4.7
通讯作者：
Wei Xu Hong
中科院分区：
文献类型：
--
作者：
Wang Wei;Zhong Xiongxiong;Li Yongyong;Guo Ruixian;Du Sujuan;Wen Lili;Ying Yanlu;Yang Tao;Wei Xu Hong
慢性术后疼痛（CPSP）仍然是一个医学问题。来自吻侧腹内侧髓质（RVM）的伤害性传递的下行调节是否在大腿皮肤/肌肉切开和收缩（SMIR）诱导的CPSP中起作用尚不清楚。在这项研究中，我们发现SMIR手术，诱导双侧或单侧机械异常性疼痛，激活小胶质细胞，上调白细胞介素- 1β (IL - 1β)，一种重要的细胞因子，和8 -羟基鸟嘌呤，RVM中的氧化应激标志物。此外，SMIR后双侧或单侧疼痛大鼠的同侧和对侧RVM中5‐羟色胺（5‐HT）的释放增加。在双侧疼痛的SMIR大鼠中，5‐HT水平升高，5‐HT3受体（5‐HT3R）上调，小胶质细胞激活，但在单侧疼痛的SMIR大鼠中，仅在同侧出现。鞘内注射5‐HT3R拮抗剂Y25130可阻止SMIR诱导的CPSP的发展和脊髓小胶质细胞的激活。此外，P2X7受体（P2X7R）在RVM小胶质细胞中上调。将P2X7R拮抗剂亮蓝G （BBG，一种非竞争性P2X7R拮抗剂）微注射到RVM中，可以阻止机械性异常痛的发展，抑制小胶质细胞的激活，并降低SMIR后RVM中IL - 1β和8 -羟基鸟嘌呤的表达。重要的是，注入RVM的BBG也降低了腰3 （L3）脊髓中小胶质细胞的激活和5‐HT的水平。将P2X7R激动剂BzATP、NADPH氧化酶激活剂phorbol‐12‐肉肉酸盐‐13‐醋酸盐或IL‐1β微量注射到RVM中，可诱导双侧机械异常性疼痛、小胶质细胞激活和L3脊髓背角5‐HT释放。综上所述，SMIR后RVM小胶质细胞中P2X7R的激活可能通过激活血清素下降通路导致CPSP的发展。开放科学徽章本文获得了*开放材料*的徽章，因为它提供了手稿中复制研究的所有相关信息。本文的完整开放科学披露表可在文章末尾找到。关于开放实践徽章的更多信息可以在https://cos.io/our-services/open-science-badges/上找到。
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‐1β (IL‐1β), 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‐1β 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‐1β 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 badgesThis 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/.