SDF1-CXCR4 Signaling Contributes to the Transition from Acute to Chronic Pain State
SDF1-CXCR4 Signaling Contributes to the Transition from Acute to Chronic Pain State
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SDF1-CXCR4 信号传导有助于从急性疼痛状态向慢性疼痛状态的转变
DOI：
10.1007/s12035-016-9875-5
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发表时间：
2017-05
影响因子：
5.1
通讯作者：
Chen Jun
中科院分区：
文献类型：
--
作者：
Yang Fei;Sun Wei;Luo Wen-Jun;Yang Yan;Yang Fan;Wang Xiao-Liang;Chen Jun
越来越多的证据表明，基质细胞衍生因子1(SDF1，又称CXCL12)-CXCR4信号参与了多种疼痛状态。然而，SDF1-CXCR4信号导致慢性疼痛状态维持的潜在机制尚不清楚。在本研究中，我们试图通过应用一种从急性疼痛状态到慢性疼痛状态的转换模型，即痛觉过敏启动，来探讨SDF1-CXCR4信号在神经可塑性形成中的作用。利用足底注射蜂毒(BV)成功地建立了痛觉过敏状态，外周注射CXCR4拮抗剂AMD3100或神经节内注射CXCR4小干扰RNA(SiRNA)阻断CXCR4均可预防BV诱导的原发机械性痛敏和痛觉过敏。此外，我们还证明，足底注射一次活性SDF1蛋白就足以通过CXC4诱导急性机械性痛敏和痛觉过敏性启动。足底联合注射ERK抑制剂U0126和PI3K抑制剂LY294002，以及两种蛋白翻译抑制剂泰西莫司和虫草素，可阻止SDF1诱导的急性机械性痛敏和痛觉过敏性启动。最后，在完全弗氏佐剂(CFA)诱导的慢性炎症性疼痛和备用神经损伤(SNI)诱导的慢性神经病理性疼痛模型上，我们观察到CXCR4的敲除既可以阻止慢性疼痛的发展，又可以逆转慢性疼痛状态的维持。综上所述，我们目前的研究结果表明，SDF1-CXCR4信号通过调节ERK和PI3K-AKT信号通路，介导了急性疼痛向慢性疼痛状态的转变，最终参与了慢性疼痛的发生和维持。
Emerging evidence has demonstrated the involvement of stromal cell-derived factor 1 (SDF1, also known as CXCL12)-CXCR4 signaling in a variety of pain state. However, the underlying mechanisms of SDF1-CXCR4 signaling leading to the maintenance of chronic pain states are poorly understood. In the present study, we sought to explore the role of SDF1-CXCR4 signaling in the forming of neuroplasticity by applying a model of the transition from acute to chronic pain state, named as hyperalgesic priming. Utilizing intraplantar bee venom (BV) injection, we successfully established hyperalgesic priming state and found that peripheral treating with AMD3100, a CXCR4 antagonist, or knocking down CXCR4 by intraganglionar CXCR4 small interfering RNA (siRNA) injection could prevent BV-induced primary mechanical hyperalgesia and hyperalgesic priming. Moreover, we showed that single intraplantar active SDF1 protein injection is sufficient to induce acute mechanical hyperalgesia and hyperalgesic priming through CXC4. Intraplantar coinjection of ERK inhibitor, U0126, and PI3K inhibitor, LY294002, as well as two protein translation inhibitors, temsirolimus and cordycepin, prevented the development of SDF1-induced acute mechanical hyperalgesia and hyperalgesic priming. Finally, on the models of complete Freund’s adjuvant (CFA)-induced chronic inflammatory pain and spared nerve injury (SNI)-induced chronic neuropathic pain, we observed that knock-down of CXCR4 could both prevent the development and reverse the maintenance of chronic pain state. In conclusion, our present data suggested that through regulating ERK and PI3K-AKT pathways-mediated protein translation SDF1-CXCR4 signaling mediates the transition from acute pain to chronic pain state and finally contributes to the development and maintenance of chronic pain.
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影响因子：
9.3
作者：
Shen W;Hu XM;Liu YN;Han Y;Chen LP;Wang CC;Song C
通讯作者：
Song C
影响因子：
2.8
作者：
Knerlich-Lukoschus, Friederike;von der Ropp-Brenner, Beata;Held-Feindt, Janka
通讯作者：
Held-Feindt, Janka
影响因子：
3.4
作者：
Limatola, C;Giovannelli, A;Eusebi, F
通讯作者：
Eusebi, F
影响因子：
5.3
作者：
Kim, Ji-Young V.;Tillu, Dipti V.;Price, Theodore J.
通讯作者：
Price, Theodore J.
影响因子：
7.4
作者：
Araldi D;Ferrari LF;Levine JD
通讯作者：
Levine JD