Spinal and Supraspinal Mechanisms of Neuropathic Pain
Spinal and Supraspinal Mechanisms of Neuropathic Pain
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DOI：
10.1111/j.1749-6632.2000.tb06673.x
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发表时间：
2000-01
影响因子：
5.2
通讯作者：
M. Ossipov;J. Lai;T. Malan;F. Porreca
中科院分区：
文献类型：
--
作者：
M. Ossipov;J. Lai;T. Malan;F. Porreca
摘要：神经病理性疼痛与异常的触觉和热反应有关，这些反应可能超出受伤神经的范围。重要的是，触觉异常性疼痛和热痛觉过敏可能涉及不同的途径，因为在脊髓神经结扎（SNL）后，完全和部分脊髓损伤阻止了异常性疼痛，但不能阻止痛觉过敏。此外，背柱损伤和微注射到背柱核中的利多卡因仅阻止触觉异常性疼痛。相反，树脂毒素的 C 纤维脱敏作用可阻断热痛觉过敏，但不能阻断触觉异常性疼痛。因此，触觉异常性疼痛可能是由大直径 Aβ 纤维介导的，并且不易受到脊髓阿片类药物的调节，而痛觉过敏是由无髓鞘 C 纤维介导的，并且对脊髓阿片类药物的阻断敏感。此外，神经病理性疼痛中异常的自发传入驱动可能通过谷氨酸和脊髓强啡肽的非阿片类药物作用导致 NMDA 介导的中枢敏化。相应地，SNL 引起受伤神经进入区及其附近的脊髓节段中脊髓强啡肽含量升高，并伴有神经性疼痛的迹象。 SNL 后，给予强啡肽 A(1-17) 或 MK-801 抗血清，脊髓可阻断热痛觉过敏，但不会出现触觉异常性疼痛，并且还能恢复减弱的吗啡抗伤害作用。最后，传入驱动可能会引起延髓头腹内侧（RVM）的下降促进。用布比卡因阻断传入驱动也可以恢复 PAG 吗啡失去的效力，RVM 中的 CCK 拮抗剂也是如此。这一观察结果与传入驱动激活 RVM 的下行促进一致，从而减少阿片类药物活性，并且可能是神经性疼痛对阿片类药物反应有限的临床观察的基础
Abstract: Neuropathic pain is associated with abnormal tactile and thermal responses that may be extraterritorial to the injured nerve. Importantly, tactile allodynia and thermal hyperalgesia may involve separate pathways, since complete and partial spinal cord lesions have blocked allodynia, but not hyperalgesia, after spinal nerve ligation (SNL). Furthermore, lesions of the dorsal column, and lidocaine microinjected into dorsal column nuclei block only tactile allodynia. Conversely, thermal hyperalgesia, but not tactile allodynia was blocked by desensitizatin of C‐fibers with resiniferotoxin. Therefore, it seems that tactile allodynia is likely to be mediated by large diameter Aβ fibers, and not susceptible to modulation by spinal opioids, whereas hyperalgesia is mediated by unmyelinated C‐fibers, and is sensitive to blockade by spinal opioids. Additionally, abnormal, spontaneous afferent drive in neuropathic pain may contribute to NMDA‐mediated central sensitization by glutamate and by non‐opioid actions of spinal dynorphin. Correspondingly, SNL elicited elevation in spinal dynorphin content in spinal segments at and adjacent to the zone of entry of the injured nerve along with signs of neuropathic pain. Antiserum to dynorphin A(1–17) or MK‐801 given spinally blocked thermal hyperalgesia, but not tactile allodynia, after SNL, and also restored diminished morphine antinociception. Finally, afferent drive may induce descending facilitation from the rostroventromedial medulla (RVM). Blocking afferent drive with bupivicaine also restored lost potency of PAG morphine, as did CCK antagonists in the RVM. This observation is consistent with afferent drive activating descending facilitation from the RVM, and thus diminishing opioid activity, and may underlie the clinical observation of limited responsiveness of neuropathic pain to opioids