Light touch induces ERK activation in superficial dorsal horn neurons after inflammation: involvement of spinal astrocytes and JNK signaling in touch-evoked central sensitization and mechanical allodynia.
Light touch induces ERK activation in superficial dorsal horn neurons after inflammation: involvement of spinal astrocytes and JNK signaling in touch-evoked central sensitization and mechanical allodynia.
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DOI：
10.1111/j.1471-4159.2010.06946.x
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发表时间：
2010-10
影响因子：
4.7
通讯作者：
Ji RR
中科院分区：
文献类型：
--
作者：
Gao YJ;Ji RR
脊髓神经元细胞外信号调节激酶（ERK）的激活可作为持续性痛时背角神经元敏感化的标志。ERK通常被高阈值伤害性刺激激活。我们研究了低阈值机械刺激如何在完全弗氏佐剂（CFA）诱导的炎症后激活ERK。单侧注射CFA可引起同侧热痛敏和双侧机械性痛觉超敏。CFA诱导的同侧背角神经元ERK激活在2天后下降。有趣的是，低阈值的机械刺激，无论是在发炎的爪子或对侧非发炎的爪子上的轻触显着增加ERK磷酸化（pERK）在同侧的背角触摸刺激。值得注意的是，轻触主要在I-IIo层的浅层神经元中诱导pERK。CFA后第2天鞘内注射星形胶质细胞毒素L-α-氨基己二酸酯（L-α-AA）可逆转CFA诱导的双侧机械性异常性疼痛，但不能逆转热痛觉过敏。此外，L-α-AA、神经胶质抑制剂氟柠檬酸盐和c-Jun N-末端激酶（JNK）的肽抑制剂均减少了光触摸诱发的ERK激活。总的来说，这些数据表明：（a）在病理条件下，低阈值机械刺激可激活浅表背角神经元中的ERK，（B）轻触激活ERK与机械异常性疼痛相关，需要星形胶质细胞网络。
Activation of extracellular signal-regulated kinase (ERK) in spinal cord neurons could serve as a marker for sensitization of dorsal horn neurons in persistent pain. ERK is normally activated by high-threshold noxious stimuli. We investigated how low-threshold mechanical stimuli could activate ERK after complete Freund’s adjuvant (CFA)-induced inflammation. Unilateral injection of CFA induced ipsilateral heat hyperalgesia and bilateral mechanical allodynia. CFA-induced ERK activation in ipsilateral dorsal horn neurons declined after 2 days. Interestingly, low threshold mechanical stimulation given by light touch either on the inflamed paw or the contralateral non-inflamed paw dramatically increased ERK phosphorylation (pERK) in the dorsal horn ipsilateral to touch stimulation. Notably, light touch induced pERK mainly in superficial neurons in laminae I-IIo. Intrathecal administration of the astroglial toxin L-α-aminoadipate (L-α-AA) on post-CFA day 2 reversed CFA-induced bilateral mechanical allodynia but not heat hyperalgesia. Furthermore, L-α-AA, the glial inhibitor fluorocitrate, and a peptide inhibitor of c-Jun N-terminal Kinase (JNK) all reduced light touch-evoked ERK activation ipsilateral to touch. Collectively, these data suggest that (a) ERK can be activated in superficial dorsal horn neurons by low threshold mechanical stimulation under pathological condition and (b) ERK activation by light touch is associated with mechanical allodynia and requires an astrocyte network.
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