Inflammation and Hypersensitivity in the Context of the Sensory Functions of Axonal Membranes: What Are the Molecular Mechanisms?
Inflammation and Hypersensitivity in the Context of the Sensory Functions of Axonal Membranes: What Are the Molecular Mechanisms?
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DOI：
10.1159/000268116
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发表时间：
2010-03
影响因子：
2.3
通讯作者：
S. Sauer;P. Reeh
中科院分区：
文献类型：
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作者：
S. Sauer;P. Reeh
背景资料：无髓鞘感觉神经纤维的轴突膜装备有不同的分子换能器分子，其建立特定的敏感性、通过炎症致敏的能力和产生异位动作电位，其有助于脊髓致敏，导致投射疼痛、异常性疼痛和痛觉过敏。研究方法：我们研究了无髓轴突的感觉特性，通过测量刺激的神经肽释放，记录从初级传入神经和诱发投射疼痛的刺激手术暴露的浅桡神经在一个有意识的人受试者。结果如下：辣椒素（TRPV 1）受体通道沿着轴突膜表达，并对酸、热和辣椒素刺激产生分级和钙依赖性降钙素基因相关肽释放。这些反应可由缓激肽或前列腺素促进，表明轴突膜上有功能性BK和EP受体沿着。TRPV 1基因敲除小鼠的制剂失去致敏作用。在分离的迷走神经，代表内脏神经支配，内源性香草素/内源性大麻素anandamide诱导或敏化降钙素基因相关肽的释放激活TRPV 1。我们的电生理记录显示异位产生的动作电位。完整的无髓鞘轴突表现出感觉能力，类似于他们的个人皮肤伤害性终端，相对于有毒的热敏感性。在人类受试者中，暴露的皮肤神经的有害热刺激在神经支配区域引起强烈的烧灼痛感觉。结论：不同的证据表明，伤害性轴突表现出的信号转导和穗产生机制的重要组成部分。当放大（例如通过炎症介质）时，这种轴突敏感性可能成为神经性疼痛的来源。
Background: The axonal membrane of unmyelinated sensory nerve fibers is well equipped with different molecular transducer molecules that establish specific sensitivities, the capacity for sensitization by inflammation and generation of ectopic action potentials that contribute to spinal sensitization, leading to projected pain, allodynia and hyperalgesia. Methods: We studied the sensory properties of unmyelinated axons in the midnerve by measuring stimulated neuropeptide release, recording from primary afferents and eliciting projected pain by stimulation of a surgically exposed superficial radial nerve in a conscious human subject. Results: Capsaicin (TRPV1) receptor channels are expressed along the axonal membrane and respond to acidic, thermal and capsaicin stimulation with a graded and calcium-dependent calcitonin gene-related peptide release. These responses can be facilitated by bradykinin or prostaglandin, indicating functional BK and EP receptors along the axonal membrane. Sensitizing effects are lost in preparations from TRPV1 knockout mice. In the isolated vagus nerve, representing visceral innervation, the endovanilloid/endocannabinoid anandamide induced or sensitized calcitonin gene-related peptide release by activation of TRPV1. Our electrophysiological recordings revealed ectopic generation of action potentials. Intact unmyelinated axons showed sensory capacities that resembled those of their individual cutaneous nociceptive terminals, with respect to noxious heat sensitivity. In the human subject, noxious heat stimulation of the exposed skin nerve evoked intense burning pain sensation in the innervation territory. Conclusion: Different lines of evidence indicate that nociceptive axons exhibit essential parts of the signal transduction and spike generation machinery. When amplified (e.g. by inflammatory mediators), this axonal sensitivity may become a source of neuropathic pain.