Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse Model.
Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse Model.
复制标题
在小鼠模型中，突破性癌症疼痛与通过调节连接蛋白 43 激活脊髓间隙连接有关。
DOI：
10.3389/fncel.2017.00207
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发表时间：
2017
影响因子：
5.3
通讯作者：
Huang D
中科院分区：
文献类型：
--
作者：
Li X;Jiang S;Yang H;Liao Q;Cao S;Yan X;Huang D
突破性癌痛（BTcP）是一种高强度、短持续时间、不可预测和无法控制的疼痛。近年来的研究表明，脊髓间隙连接（GJ）的激活在BTcP的发病机制中起重要作用。本实验检测了小鼠脊髓胶质细胞酸性蛋白（GFAP）、连接蛋白（Cx）43蛋白的表达及Cx43磷酸化（p-Cx43）。此外，我们还观察了选择性GJ阻断剂Gap 26对BTcP小鼠GFAP、Cx43和p-Cx43表达的影响。我们发现，在BTcP小鼠模型中，脊髓中GFAP和Cx43蛋白的表达显著上调，而p-Cx43则下调。Cx43蛋白在脊髓中的过表达增加了GJ的形成，并增强了BTcP。p-Cx43/T-Cx43（总Cx43）比值的变化影响GJ诱导BTcP的功能。此外，Gap 26通过降低疼痛超敏性来减轻BTcP。Gap 26对Cx43和p-Cx43的抑制使BTcP减弱，但在BTcP小鼠中Cx43的p/T比率保持不变。我们发现，Cx43的表达和磷酸化影响BTcP和GJ激活促进BTcP通过Cx43介导的信号在脊髓中。这一发现可能为临床上发现和开发治疗BTcP的新靶点提供科学依据。
Breakthrough cancer pain (BTcP) is a high-intensity, short-duration, unpredictable and uncontrollable pain. Recent studies have shown that activation of gap junction (GJ) in spinal cord plays an important role in the pathogenesis of BTcP. We examined the expressions of Glial fibrillary acidic protein (GFAP), connexin (Cx) 43 protein and phosphorylation of Cx43 (p-Cx43) in the spinal cord of mice. In addition, we investigated the effects of Gap26, a selective GJ blocker, on the expressions of GFAP, Cx43 and p-Cx43 in BTcP mice. We found that the expressions of GFAP and Cx43 proteins were significantly upregulated while p-Cx43 was down-regulated in the spinal cord in a mouse model of BTcP. The overexpression of Cx43 protein in the spinal cord increased GJ formation and enhanced BTcP. The variation of the ratio of p-Cx43/T-Cx43 (total Cx43) affected the function of GJ to induce BTcP. Furthermore, BTcP was alleviated by Gap26 via reducing pain hypersensitivity. The inhibition of Cx43 and p-Cx43 by Gap26 attenuated BTcP but the p/T ratio of Cx43 remained unchanged in BTcP mice. We reveal that the expression and phosphorylation of Cx43 affected BTcP and GJ activation facilitated BTcP via a Cx43-mediated signaling in the spinal cord. The finding may provide a scientific rationale for discovery and development of novel therapeutic targets for the treatment of BTcP clinically.
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