Institute of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Erlangen, Germany.
Dig Dis. 2009;27 Suppl 1:11-5. doi: 10.1159/000268116. Epub 2010 Mar 4.
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.
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.
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.
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.
未髓鞘感觉神经纤维的轴突膜上配备有不同的分子转导分子，这些分子决定了感觉的特异性、对炎症的敏感性以及产生异位动作电位的能力，这些都有助于脊髓敏化，导致投射性疼痛、痛觉过敏和痛觉超敏。
我们通过测量刺激神经肽释放、记录初级传入纤维和刺激暴露的桡浅神经诱发投射性疼痛来研究中神经无髓纤维的感觉特性，该研究在一位意识清醒的人类受试者中进行。
辣椒素（TRPV1）受体通道沿轴突膜表达，对酸性、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。这种反应可以被缓激肽或前列腺素促进，表明沿轴突膜存在功能性 BK 和 EP 受体。在 TRPV1 基因敲除小鼠的标本中，这种敏化作用消失。在代表内脏传入的分离迷走神经中，内源性大麻素/内源性大麻素激动剂大麻素通过激活 TRPV1 诱导或敏化降钙素基因相关肽释放。我们的电生理记录显示异位动作电位的产生。完整的无髓纤维表现出与单个皮肤伤害性末端相似的感觉能力，表现为对有害热的敏感性。在人类受试者中，暴露皮肤神经的有害热刺激在其支配区域诱发强烈的烧灼感。
不同的证据表明伤害性轴突表现出信号转导和锋电位产生机制的重要部分。当这种轴突敏感性被放大（例如通过炎症介质）时，它可能成为神经病理性疼痛的来源。
