ERK MAP kinase activation in superficial spinal cord neurons induces prodynorphin and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity
ERK MAP kinase activation in superficial spinal cord neurons induces prodynorphin and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity
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DOI：
10.1523/jneurosci.22-02-00478.2002
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发表时间：
2002-01-15
影响因子：
5.3
通讯作者：
Woolf, CJ
中科院分区：
文献类型：
--
作者：
Ji, RR;Befort, K;Woolf, CJ
外周伤害性刺激激活脊髓背角神经元的ERK（细胞外信号调节激酶）MAP（丝裂原活化蛋白）激酶有助于短期疼痛超敏反应。我们研究了外周炎症引起的ERK激活及其参与调节脊髓基因表达和促进炎性疼痛超敏反应。将完全弗氏佐剂（CFA）注射到后爪中产生了持续的炎症和背角浅层（层I-llo）中神经元中的持续ERK激活。CFA还诱导背角神经元中强啡肽原和神经激肽-1（NK-1）的上调，这被MEK（MAP激酶激酶）抑制剂U 0126的鞘内递送所抑制。CFA诱导的磷酸化ERK主要与前强啡肽和NK-1共定位于背角浅层神经元。虽然鞘内注射U 0126不影响基础疼痛敏感性，但它确实减弱了持续性炎性热和机械超敏反应的建立和维持。因此，在伤害感受性脊髓神经元的亚群中ERK通路的激活有助于持续性疼痛超敏反应，这可能通过基因（如强啡肽原和NK-1）的转录调节。
Activation of ERK (extracellular signal-regulated kinase) MAP (mitogen-activated protein) kinase in dorsal horn neurons of the spinal cord by peripheral noxious stimulation contributes to short-term pain hypersensitivity. We investigated ERK activation by peripheral inflammation and its involvement in regulating gene expression in the spinal cord and in contributing to inflammatory pain hypersensitivity. Injection of complete Freund's adjuvant (CFA) into a hindpaw produced a persistent inflammation and a sustained ERK activation in neurons in the superficial layers (laminae l-llo) of the dorsal horn. CFA also induced an upregulation of prodynorphin and neurokinin-1 (NK-1) in dorsal horn neurons, which was suppressed by intrathecal delivery of the MEK (MAP kinase kinase) inhibitor U0126. CFA-induced phospho-ERK primarily colocalized with prodynorphin and NK-1 in superficial dorsal horn neurons. Although intrathecal injection of U0126 did not affect basal pain sensitivity, it did attenuate both the establishment and maintenance of persistent inflammatory heat and mechanical hypersensitivity. Activation of the ERK pathway in a subset of nociceptive spinal neurons contributes, therefore, to persistent pain hypersensitivity, possibly via transcriptional regulation of genes, such as prodynorphin and NK-1.