Dina Olayinka A, McCarter Gordon C, de Coupade Catherine, Levine Jon D
Department of Medicine, Division of Neuroscience and Biomedical Sciences Program, NIH Pain Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Neuron. 2003 Aug 14;39(4):613-24. doi: 10.1016/s0896-6273(03)00473-2.
Prostaglandin E(2) (PGE(2)) and epinephrine act directly on nociceptors to produce mechanical hyperalgesia through protein kinase A (PKA) alone or through a combination of PKA, protein kinase C epsilon (PKCepsilon), and extracellular signal-regulated kinase (ERK), respectively. Disruptors of the cytoskeleton (microfilaments, microtubules, and intermediate filaments) markedly attenuated the hyperalgesia in rat paws caused by injection of epinephrine or its downstream mediators. In contrast, the hyperalgesia induced by PGE(2) or its mediators was not affected by any of the cytoskeletal disruptors. These effects were mimicked in vitro, as measured by enhancement of the tetrodotoxin-resistant sodium current. When PGE(2) hyperalgesia was shifted to dependence on PKCepsilon and ERK as well as PKA, as when the tissue is "primed" by prior treatment with carrageenan, it too became dependent on an intact cytoskeleton. Thus, inflammatory mediator-induced mechanical hyperalgesia was differentially dependent on the cytoskeleton such that cytoskeletal dependence correlated with mediation by PKCepsilon and ERK.
前列腺素E(2)（PGE(2)）和肾上腺素分别单独通过蛋白激酶A（PKA）或通过PKA、蛋白激酶Cε（PKCε）和细胞外信号调节激酶（ERK）的组合直接作用于伤害感受器，产生机械性痛觉过敏。细胞骨架（微丝、微管和中间丝）的破坏剂显著减轻了因注射肾上腺素或其下游介质而导致的大鼠爪部痛觉过敏。相比之下，PGE(2)或其介质诱导的痛觉过敏不受任何细胞骨架破坏剂的影响。这些效应在体外也有体现，通过增强河豚毒素抗性钠电流来测量。当PGE(2)诱导的痛觉过敏像在组织经角叉菜胶预处理“致敏”时那样转变为依赖PKCε、ERK以及PKA时，它也变得依赖完整的细胞骨架。因此，炎症介质诱导的机械性痛觉过敏对细胞骨架的依赖存在差异，使得细胞骨架依赖性与PKCε和ERK介导的过程相关。
