Contribution of afferent pathways to nerve injury-induced spontaneous pain and evoked hypersensitivity.
Contribution of afferent pathways to nerve injury-induced spontaneous pain and evoked hypersensitivity.
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DOI：
10.1016/j.pain.2011.04.020
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发表时间：
2011-09
期刊：
影响因子：
7.4
通讯作者：
Porreca F
中科院分区：
文献类型：
--
作者：
King T;Qu C;Okun A;Mercado R;Ren J;Brion T;Lai J;Porreca F
神经性疼痛患者的主要主诉是自发性疼痛，通常被描述为“烧灼感”。最近的研究表明，负强化可以用来揭露自发性神经病理性疼痛，允许机制的调查。在这里，上行通路，可能有助于诱发和自发成分的实验性神经病理性疼痛模型进行了探讨。全身性树脂毒素（RTX）脱敏TRPV 1阳性纤维取消脊神经结扎（SNL）损伤引起的热过敏和自发性疼痛，但对触觉过敏没有影响。脊髓NK-1受体表达神经元的消融阻断了SNL诱导的热和触觉超敏反应以及自发性疼痛。神经损伤后，神经肽Y（NPY）的上调几乎只在大直径纤维中观察到，而在脑干中这些纤维的靶点失活。股薄肌可防止触觉过敏，但不能防止热过敏。阻断n内的NPY信号。股薄肌未能阻断SNL诱导的自发性疼痛或热痛觉过敏，而完全逆转触觉过敏。此外，在n.股薄肌产生强烈的触觉过敏，但未能诱导条件性位置厌恶。这些数据表明，自发性神经病理性疼痛和热痛觉过敏是由TRPV 1阳性纤维和脊髓NK-1阳性上行投射介导的。相反，大直径的背柱投射可以介导神经损伤引起的触觉过敏，但不有助于自发性疼痛。由于触觉超敏反应的抑制可以通过脊髓操作或通过神经内信号的失活来实现。在股薄肌中，由触觉刺激诱发的增强的缩爪反应不一定反映“异常性疼痛”。
A predominant complaint in patients with neuropathic pain is spontaneous pain, often described as “burning”. Recent studies have demonstrated that negative reinforcement can be used to unmask spontaneous neuropathic pain allowing for mechanistic investigations. Here, ascending pathways that might contribute to evoked and spontaneous components of experimental neuropathic pain model were explored. Desensitization of TRPV1 positive fibers with systemic resiniferatoxin (RTX) abolished spinal nerve ligation (SNL) injury-induced thermal hypersensitivity and spontaneous pain, but had no effect on tactile hypersensitivity. Ablation of spinal NK-1 receptor expressing neurons blocked SNL-induced thermal and tactile hypersensitivity as well as spontaneous pain. Following nerve injury, upregulation of neuropeptide Y (NPY) is observed almost exclusively in large diameter fibers and inactivation of the brainstem target of these fibers in the n. gracilis prevents tactile, but not thermal, hypersensitivity. Blockade of NPY signaling within the n. gracilis failed to block SNL-induced spontaneous pain or thermal hyperalgesia while fully reversing tactile hypersensitivity. Moreover, microinjection of NPY into n. gracilis produced robust tactile hypersensitivity, but failed to induce conditioned place aversion. These data suggest that spontaneous neuropathic pain and thermal hyperalgesia are mediated by TRPV1 positive fibers and spinal NK-1 positive ascending projections. In contrast, the large diameter dorsal column projection can mediate nerve injury-induced tactile hypersensitivity, but does not contribute to spontaneous pain. As inhibition of tactile hypersensitivity can be achieved either by spinal manipulations or by inactivation of signaling within the n. gracilis, the enhanced paw withdrawal response evoked by tactile stimulation does not necessarily reflect “allodynia”.
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