Fast-conducting mechanoreceptors contribute to withdrawal behavior in normal and nerve injured rats.
Fast-conducting mechanoreceptors contribute to withdrawal behavior in normal and nerve injured rats.
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DOI：
10.1016/j.pain.2014.09.030
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发表时间：
2014-12
期刊：
影响因子：
7.4
通讯作者：
Ririe DG
中科院分区：
文献类型：
--
作者：
Boada DM;Martin TJ;Peters CM;Hayashida K;Harris MH;Houle TT;Boyden ES;Eisenach JC;Ririe DG
快速传导髓鞘高阈机械感受器（AHTMR）被广泛认为是从外周传递急性伤害感觉。然而，它们在正常戒断和神经损伤引起的痛觉过敏中的作用尚不为人所接受。外周神经元亚群的调节将有助于确定它们在戒断行为中的作用。将光活性质子泵ArchT置于带有CAG启动子的AAV8病毒载体中，并通过鞘内注射使其在有髓鞘神经元中表达。在表达ArchT的神经元中，胞体和经皮对周围神经元的光抑制是可能的，而在对照动物的神经元中则没有。感受野特征和电生理学确定抑制是神经元亚型特异性的，只有AHTMR神经元被抑制。神经损伤后一周，AHTMR呈高兴奋性，但在胞体和经皮仍可被抑制。在正常和痛觉神经损伤动物的机械刺激下，经皮光照射后爪也增加了戒断阈值。这表明AHTMR神经元不仅在正常动物阈值相关戒断行为中起作用，而且在神经损伤后的致敏状态中也起作用。这是第一次对神经元亚群进行可逆调节，以测试它们在神经损伤前后对戒断相关行为的贡献。这项技术可能有助于确定不同疼痛状态下选择性神经元群的作用。
Fast conducting myelinated high threshold mechanoreceptors (AHTMR) are largely thought to transmit acute nociception from the periphery. However, their roles in normal withdrawal and in nerve injury induced hyperalgesia are less well accepted. Modulation of this subpopulation of peripheral neurons would help define their roles in withdrawal behaviors. The optically active proton pump, ArchT, was placed in an AAV8 viral vector with the CAG promoter and was administered by intrathecal injection resulting in expression in myelinated neurons. Optical inhibition of peripheral neurons at the soma and transcutaneously was possible in the neurons expressing ArchT, but not in neurons from control animals. Receptive field characteristics and electrophysiology determined that inhibition was neuronal subtype specific with only AHTMR neurons being inhibited. One week following nerve injury the AHTMR are hyperexcitable, but can still be inhibited at the soma and transcutaneously. Withdrawal thresholds to mechanical stimuli in normal and in hyperalgesic nerve injured animals were also increased by transcutaneous light to the affected hindpaw. This suggests that AHTMR neurons play a role not only in threshold related withdrawal behavior in the normal animal, but also in sensitized states after nerve injury. This is the first time this subpopulation of neurons has been reversibly modulated to test their contribution to withdrawal related behaviors before and after nerve injury. This technique may prove useful to define the role of selective neuronal populations in different pain states.
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