TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury
TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury
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DOI：
10.1172/jci23437
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发表时间：
2005-09-01
影响因子：
15.9
通讯作者：
Noguchi, K
中科院分区：
文献类型：
--
作者：
Obata, K;Katsura, H;Noguchi, K
冷痛过敏是炎症性和神经性疼痛的一种有充分证据的症状；然而，这种对寒冷的敏感性增强的潜在机制尚不清楚。瞬时受体电位（TRP）通道的一个子集介导热感觉，并在感觉组织中表达，如伤害感受器和皮肤。在这里，我们报道了初级感觉神经元中TRPA1的药物阻断逆转了由炎症和神经损伤引起的冷痛觉过敏。炎症和神经损伤增加了TRPA1在表达酪氨酸激酶a的背根神经节（DRG）神经元中的表达，而不增加TRPM8的表达。鞘内给予抗神经生长因子（抗ngf）、p38 MAPK抑制剂或TRPA1反义寡核苷酸可减少TRPA1的诱导，并抑制炎症和神经损伤引起的冷痛过敏。相反，鞘内注射NGF，而不是胶质细胞系来源的神经营养因子，通过p38 MAPK途径增加DRG神经元中的TRPA1。综上所述，这些结果表明ngf通过p38激活诱导感觉神经元TRPA1增加是冷痛觉过敏所必需的。因此，阻断感觉神经元中的TRPA1可能为治疗由炎症和神经损伤引起的冷痛觉过敏提供了一种富有成效的策略。
Cold hyperalgesia is a well-documented symptom of inflammatory and neuropathic pain; however, the underlying mechanisms of this enhanced sensitivity to cold are poorly understood. A subset of transient receptor potential (TRP) channels mediates thermosensation and is expressed in sensory tissues, such as nociceptors and skin. Here we report that the pharmacological blockade of TRPA1 in primary sensory neurons reversed cold hyperalgesia caused by inflammation and nerve injury. Inflammation and nerve injury increased TRPA1, but not TRPM8, expression in tyrosine kinase A-expressing dorsal root ganglion (DRG) neurons. Intrathecal administration of anti-nerve growth factor (anti-NGF), p38 MAPK inhibitor, or TRPA1 antisense oligode-oxynucleotide decreased the induction of TRPA1 and suppressed inflammation- and nerve injury-induced cold hyperalgesia. Conversely, intrathecal injection of NGF, but not glial cell line-derived neurotrophic factor, increased TRPA1 in DRG neurons through the p38 MAPK pathway. Together, these results demonstrate that an NGF-induced TRPA1 increase in sensory neurons via p38 activation is necessary for cold hyperalgesia. Thus, blocking TRPA1 in sensory neurons might provide a fruitful strategy for treating cold hyperalgesia caused by inflammation and nerve damage.