Delta opioid receptors presynaptically regulate cutaneous mechanosensory neuron input to the spinal cord dorsal horn.
Delta opioid receptors presynaptically regulate cutaneous mechanosensory neuron input to the spinal cord dorsal horn.
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DOI：
10.1016/j.neuron.2014.01.044
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发表时间：
2014-03-19
期刊：
影响因子：
16.2
通讯作者：
Scherrer G
中科院分区：
文献类型：
--
作者：
Bardoni R;Tawfik VL;Wang D;François A;Solorzano C;Shuster SA;Choudhury P;Betelli C;Cassidy C;Smith K;de Nooij JC;Mennicken F;O'Donnell D;Kieffer BL;Woodbury CJ;Basbaum AI;MacDermott AB;Scherrer G
皮肤机械感觉神经元检测产生触觉和痛觉的机械刺激。虽然阿片类药物一般只与疼痛的控制，在这里，我们报告说，阿片类药物系统实际上广泛调节皮肤机械感觉，包括触摸。这种功能主要由δ阿片受体（DOR）辅助，其由形成迈斯纳小体、默克尔细胞-神经突复合物和周向毛囊末梢的有髓鞘机械感受器表达。这些传入还包括一小部分表达CGRP的有髓伤害感受器，我们现在将其鉴定为共表达μ和δ阿片受体的体感神经元。我们进一步证明，DOR激活中枢终末的有髓机械感受器抑制突触输入脊髓背角，通过抑制电压门控钙通道。总的来说，我们的研究结果揭示了阿片类药物调节皮肤机械感觉的分子机制，并为靶向DOR以减轻损伤诱导的机械超敏反应提供了理论基础。
Cutaneous mechanosensory neurons detect mechanical stimuli that generate touch and pain sensation. Although opioids are generally associated only with the control of pain, here we report that the opioid system in fact broadly regulates cutaneous mechanosensation, including touch. This function is predominantly subserved by the delta opioid receptor (DOR), which is expressed by myelinated mechanoreceptors that form Meissner corpuscles, Merkel cell-neurite complexes, and circumferential hair follicle endings. These afferents also include a small population of CGRP-expressing myelinated nociceptors that we now identify as the somatosensory neurons that coexpress mu and delta opioid receptors. We further demonstrate that DOR activation at the central terminals of myelinated mechanoreceptors depresses synaptic input to the spinal dorsal horn, via the inhibition of voltage-gated calcium channels. Collectively our results uncover a molecular mechanism by which opioids modulate cutaneous mechanosensation and provide a rationale for targeting DOR to alleviate injury-induced mechanical hypersensitivity.
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