Stress exacerbates neuropathic pain via glucocorticoid and NMDA receptor activation.
Stress exacerbates neuropathic pain via glucocorticoid and NMDA receptor activation.
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DOI：
10.1016/j.bbi.2009.04.001
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发表时间：
2009-08
影响因子：
15.1
通讯作者：
Popovich, Phillip G.
中科院分区：
文献类型：
--
作者：
Alexander, Jessica K.;DeVries, A. Courtney;Kigerl, Kristina A.;Dahlman, Jason M.;Popovich, Phillip G.
越来越多的人认识到心理压力会影响疼痛。包括对应激的生理反应的激素（例如皮质酮; CORT）可以与神经性疼痛的效应物相互作用。为了验证这一假设，小鼠在暴露于60分钟束缚应激后接受备用神经损伤（SNI）。在应激小鼠中，异常性疼痛持续增加。加剧疼痛反应的潜在机制涉及CORT通过糖皮质激素受体（GR）起作用; GR拮抗剂RU 486可防止应激诱导的异常性疼痛增加，而向非应激小鼠外源性给予CORT可重现应激引起的异常性疼痛反应。由于神经损伤诱导的小胶质细胞活化与神经病理性疼痛的发生和传播有关，因此我们评估了应激背景下小胶质细胞活化的细胞和分子指标。背角小胶质细胞的激活被应激加速;然而，这种效应是短暂的，并且与促炎表型的发生或维持无关。应激增强的异常性疼痛与背角细胞外信号调节激酶磷酸化（pERK）增加有关。ERK激活可能表明应激介导的谷氨酸能信号传导增加，因此在SNI和应激之前用美金刚（一种N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂）处理小鼠。美金刚可防止SNI后应激诱导的异常性疼痛增强。这些数据表明，激素反应引起的压力加剧神经性疼痛，通过增强中枢敏化。此外，抑制糖皮质激素（GC）和/或NMDAR信号传导的药物可以改善由压力引起的疼痛综合征。
There is growing recognition that psychological stress influences pain. Hormones that comprise the physiological response to stress (e.g. corticosterone; CORT) may interact with effectors of neuropathic pain. To test this hypothesis, mice received a spared nerve injury (SNI) after exposure to 60 min restraint stress. In stressed mice, allodynia was consistently increased. The mechanism(s) underlying the exacerbated pain response involves CORT acting via glucocorticoid receptors (GRs); RU486, a GR antagonist, prevented the stress-induced increase in allodynia whereas exogenous administration of CORT to non-stressed mice reproduced the allodynic response caused by stress. Since nerve injury-induced microglial activation has been implicated in the onset and propagation of neuropathic pain, we evaluated cellular and molecular indices of microglial activation in the context of stress. Activation of dorsal horn microglia was accelerated by stress; however, this effect was transient and was not associated with the onset or maintenance of a pro-inflammatory phenotype. Stress-enhanced allodynia was associated with increased dorsal horn extracellular signal-regulated kinase phosphorylation (pERK). ERK activation could indicate a stress-mediated increase in glutamatergic signaling, therefore mice were treated prior to SNI and stress with memantine, an N-methyl-D-aspartate receptor (NMDAR) antagonist. Memantine prevented stress-induced enhancement of allodynia after SNI. These data suggest that the hormonal responses elicited by stress exacerbate neuropathic pain through enhanced central sensitization. Moreover, drugs that inhibit glucocorticoids (GCs) and/or NMDAR signaling could ameliorate pain syndromes caused by stress.
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影响因子：
2.9
作者：
DeLeo, JA;Colburn, RW;Rickman, AJ
通讯作者：
Rickman, AJ
DOI：
10.1073/pnas.92.17.7744
发表时间：
1995-08-15
影响因子：
11.1
作者：
DEVRIES, AC;DEVRIES, MB;CARTER, CS
通讯作者：
CARTER, CS
影响因子：
2.9
作者：
Bomholt, SF;Mikkelsen, JD;Blackbum-Munro, G
通讯作者：
Blackbum-Munro, G
影响因子：
3.3
作者：
Cho, K;Little, HJ
通讯作者：
Little, HJ
影响因子：
3.8
作者：
Drew, PD;Chavis, JA
通讯作者：
Chavis, JA