The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.
The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.
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DOI：
10.1371/journal.pone.0007383
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发表时间：
2009-10-08
期刊：
影响因子：
3.7
通讯作者：
Heppenstall PA
中科院分区：
文献类型：
--
作者：
Caspani O;Zurborg S;Labuz D;Heppenstall PA
冷痛是神经病理性疼痛的一个共同特征，然而这种对冷的敏感性增强的潜在机制尚不清楚。最近，瞬时受体电位(Trp)通道TRPM8和TRPA1已被鉴定出来，并被认为是寒冷的分子传感器。在此，我们研究了TRPM8和TRPA1在背根节(DRG)中的表达，并检测了慢性建筑损伤(CCI)小鼠神经病理性疼痛模型中外周感觉神经元的冷敏感性。在行为学实验中，坐骨神经慢性压迫损伤(CCI)导致对寒冷和TRPM8激动剂薄荷醇的超敏反应，损伤后2天出现，并保持稳定至少2周。应用定量RT-PCR和原位杂交技术检测TRPM8和TRPA1在DRG中的表达。损伤后，这两个通道的表达水平都显著降低，但在已识别的神经元亚群中，它们的分布模式没有改变。此外，在钙成像实验中，我们没有发现DRG中冷或薄荷醇反应神经元的数量发生变化，也没有发现损伤后冷传导的功能特性发生变化。然而，有趣的是，对TRPA1激动剂芥子油的反应显著降低。我们的结果表明，在慢性挤压损伤后，受损的感觉神经元不会发展出异常的冷敏感性，TRPM8和TRPA1表达的变化不太可能直接参与这种神经病理性疼痛模型中冷痛的发病机制。
Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP) channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG) and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI) model of neuropathic pain in mice. In behavioral experiments, chronic constriction injury (CCI) of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced. Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.
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影响因子：
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