GABAB receptor activation attenuates inflammatory orofacial pain by modulating interleukin-1β in satellite glial cells: Role of NF-κB and MAPK signaling pathways
GABAB receptor activation attenuates inflammatory orofacial pain by modulating interleukin-1β in satellite glial cells: Role of NF-κB and MAPK signaling pathways
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DOI：
10.1016/j.brainresbull.2019.04.018
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发表时间：
2019-07-01
影响因子：
3.8
通讯作者：
Shen, Jie-Fei
中科院分区：
文献类型：
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作者：
Liu, Fei;Zhang, Yan-Yan;Shen, Jie-Fei
口面部炎症可以激活三叉神经节 (TG) 中的卫星胶质细胞 (SGC) 产生白细胞介素 1 β (IL-1 β)，其在炎性疼痛的发生中起着至关重要的作用。最近的研究表明，γ-氨基丁酸-B (GABA(B)) 受体可以调节脊髓小胶质细胞和星形胶质细胞中炎症细胞因子的表达。本研究的目的是探讨 TG SGC 中的 GABA(B) 受体是否通过介导炎症后的 IL-1β 来减轻炎症性面部疼痛及其机制。将完全弗氏佐剂（CFA）注射到大鼠的胡须垫中以诱导体内炎症。将脂多糖（LPS）添加到培养基中以在体外激活SGC。行为测量表明，将巴氯芬（一种选择性 GABA(B) 受体激动剂）微量注射到 TG 中可改善 CFA 治疗大鼠的机械异常性疼痛。有趣的是，巴氯芬预处理抑制了SGC的激活和IL-1β的产生，然而，在体内CFA和体外LPS激活的SGC中保留了GABA(B)受体表达的降低。此外，巴氯芬抑制体外LPS处理的SGC中p-NF-kappa B p65、p-I kappa B α和p-p38 MAPK表达的增加，同时逆转I kappa B α产量的减少，并进一步增强p-ERK(1/2)表达的增加。最后，与沙氯芬（一种特定的 GABA(B) 受体拮抗剂）共同给药消除了巴氯芬的这些作用。总之，这些结果首次证明，GABA(B) 受体的激活可能通过抑制 NF-kappa B 和 p38 MAPK 信号通路激活来抑制 IL-1 β 的产生，并恢复 SGC 中的 GABA(B) 受体表达，从而减轻炎症性面部疼痛
Orofacial inflammation could activate satellite glial cells (SGCs) in the trigeminal ganglion (TG) to produce interleukin 1 beta (IL-1 beta) which plays crucial roles in the development of inflammatory pain. Recent studies have shown that gamma-amino butyric acid-B (GABA(B)) receptor could modulate the expression of inflammatory cytokines in microglia and astrocytes in the spinal cord. The objective of this study was to investigate whether GABA(B) receptors in TG SGCs attenuate inflammatory facial pain via mediating IL-1 beta following inflammation and its mechanisms. Complete Freund's adjuvant (CFA) was injected into the whisker pad of rats to induce inflammation in vivo. Lipopolysaccharide (LPS) was added to culture medium to activate SGCs in vitro. Behavioral measures showed that microinjection of baclofen (a selective GABA(B) receptor agonist) into the TG ameliorated the mechanical allodynia of CFA-treated rats. Interestingly, baclofen pretreatment inhibited SGC activation and IL-1 beta production, however, preserved the decreased expression of GABA(B) receptors in SGCs activated by CFA in vivo and LPS in vitro. In addition, baclofen suppressed the increased expression of p-NF- kappa B p65, p-I kappa B alpha, and p-p38 MAPK, while reversed the decreased production of I kappa B alpha, and further enhanced the increased expression of p-ERK(1/2) in LPS-treated SGCs in vitro. Finally, those effects of baclofen were abolished by saclofen (a specific GABA(B) receptor antagonist) co-administration. Altogether, these results demonstrated for the first time that activation of GABA(B) receptor might inhibit IL-1 beta production by suppressing NF- kappa B and p38 MAPK signaling pathway activation and restore GABA(B) receptor expression in SGCs to attenuate inflammatory facial pain