Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli
Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli
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DOI：
10.1073/pnas.0901507106
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发表时间：
2009-06-02
影响因子：
11.1
通讯作者：
Anderson, David J.
中科院分区：
文献类型：
--
作者：
Cavanaugh, Daniel J.;Lee, Hyosang;Anderson, David J.
对疼痛刺激的行为反应需要称为伤害感受器的外周感觉神经元。电生理学研究表明，大多数C纤维伤害性感受器是多模态的（即。例如，对多种有害刺激形式（例如机械和热）作出反应;然而，这些刺激被感知为不同的。因此，人们认为，这些模式之间的歧视只发生在脊柱或脊髓上的处理水平。在这里，我们提供了相反的证据。成年期表达G蛋白偶联受体Mrgprd的无髓鞘感觉神经元的基因消融降低了对有害机械刺激的行为敏感性，但对热或冷刺激不敏感。相反，TRPV 1（+）伤害感受器的中央分支（构成非重叠群体）的药物消融选择性地消除了有害的热痛敏感性。两个群体的联合消除产生了加性表型，没有额外的行为缺陷，排除了这些群体对热和机械疼痛敏感性的多余贡献。这种双重分离表明，大脑可以区分不同的伤害性刺激形式的感觉处理的最早阶段。
Behavioral responses to painful stimuli require peripheral sensory neurons called nociceptors. Electrophysiological studies show that most C-fiber nociceptors are polymodal (i. e., respond to multiple noxious stimulus modalities, such as mechanical and thermal); nevertheless, these stimuli are perceived as distinct. Therefore, it is believed that discrimination among these modalities only occurs at spinal or supraspinal levels of processing. Here, we provide evidence to the contrary. Genetic ablation in adulthood of unmyelinated sensory neurons expressing the G protein-coupled receptor Mrgprd reduces behavioral sensitivity to noxious mechanical stimuli but not to heat or cold stimuli. Conversely, pharmacological ablation of the central branches of TRPV1(+) nociceptors, which constitute a nonoverlapping population, selectively abolishes noxious heat pain sensitivity. Combined elimination of both populations yielded an additive phenotype with no additional behavioral deficits, ruling out a redundant contribution of these populations to heat and mechanical pain sensitivity. This double-dissociation suggests that the brain can distinguish different noxious stimulus modalities from the earliest stages of sensory processing.