NEUROGENIC HYPERALGESIA - THE SEARCH FOR THE PRIMARY CUTANEOUS AFFERENT-FIBERS THAT CONTRIBUTE TO CAPSAICIN-INDUCED PAIN AND HYPERALGESIA
NEUROGENIC HYPERALGESIA - THE SEARCH FOR THE PRIMARY CUTANEOUS AFFERENT-FIBERS THAT CONTRIBUTE TO CAPSAICIN-INDUCED PAIN AND HYPERALGESIA
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DOI：
10.1152/jn.1991.66.1.212
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发表时间：
1991-07-01
影响因子：
2.5
通讯作者：
LAMOTTE, RH
中科院分区：
文献类型：
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作者：
BAUMANN, TK;SIMONE, DA;LAMOTTE, RH
1.局部皮肤损伤可在损伤区域内产生原发性痛觉过敏，并在正常周围皮肤中产生继发性痛觉过敏。皮内注射辣椒素会对周围皮肤的热刺激和机械刺激产生强烈的疼痛和痛觉过敏。对人类的心理物理学研究支持这样的结论，即痛觉过敏主要是继发性的，并且依赖于一组神经元敏化另一组神经元（“神经源性痛觉过敏”），并且后一组神经元位于中枢而不是外周神经系统。为了进一步验证这一假设并寻找局部损伤引起疼痛和神经源性痛觉过敏的外周神经机制，我们在猴（Macaca fascicularis）中进行了神经生理学实验，并记录了皮肤初级传入纤维对皮内注射辣椒素以及注射前后给予的机械和热刺激的反应。大多数C-和A-纤维mechanoheat-sensitive伤害性传入纤维（CMH和AMH，分别）反应太弱或短暂的辣椒素定量辣椒素疼痛的幅度。在用辣椒素注射测试的已知初级传入神经中，只有热选择性伤害感受器的反应可能解释人类心理学测量的疼痛。此外，一种新型的初级传入-暂时称为“化学伤害感受”-可能也有贡献。在感受野（RF）外部、附近或内部注射辣椒素后，伤害性感受纤维对机械或热刺激均不敏感;发生的任何变化都不能解释在人类中观察到的对机械或热刺激的痛觉过敏。在将辣椒素注射到猴子的RF内之后，猴子中的有髓鞘和无髓鞘伤害感受纤维对注射部位的热和/或机械刺激的降低的反应性（“脱敏”）与在人类中的辣椒素注射部位处观察到的镇痛相关。辣椒素，局部应用于RF在车辆的二甲基亚砜或酒精，兴奋CMH和AMH和增强的反应，这些纤维的一些热和/或抚摸皮肤。在某些情况下，单独使用溶剂也会产生类似的结果。然而，辣椒素而不是媒介物降低了一些CMH对热的阈值。因此，CMH的致敏作用有助于已知在直接暴露于局部施用的辣椒素的皮肤区域内发生的原发性痛觉过敏。我们的结论是：1）CMH和AMH的脱敏有助于在注射辣椒素的部位产生的皮肤镇痛和2）延长神经源性痛觉过敏加热和机械刺激周围的皮肤皮内注射辣椒素是不占的外周伤害性感受器的敏化。据推测，致敏神经元的神经源性痛觉过敏是位于中枢神经系统。
1. A local cutaneous injury can produce primary hyperalgesia within the injured area and secondary hyperalgesia in the normal surrounding skin. An intradermal injection of capsaicin in humans causes intense pain and hyperalgesia to heat and to mechanical stimuli in the surrounding skin. Psychophysical studies in humans supported the conclusions that the hyperalgesia was predominantly the secondary type and depended on one set of neurons sensitizing another ("neurogenic hyperalgesia") and that the latter set of neurons is located in the central and not the peripheral nervous system. To further test this hypothesis and to search for peripheral neural mechanisms contributing to the pain and neurogenic hyperalgesia from a local injury, we performed neurophysiological experiments in the monkey (Macaca fascicularis) and recorded the responses of cutaneous primary afferent fibers to an intradermal injection of capsaicin and to mechanical and heat stimuli delivered before and after the injection.2. Most C- and A-fiber mechanoheat-sensitive nociceptive afferent fibers (CMHs and AMHs, respectively) responded too weakly or transiently to capsaicin to account quantitatively for the magnitude of capsaicin pain. Of the known primary afferents tested with capsaicin injections, only the responses of heat-selective nociceptors could potentially account for the pain measured psychophysically in the human. In addition, a novel type of primary afferent-tentatively termed "chemonociceptive"-may have contributed as well.3. Nociceptive fibers did not become sensitized to either mechanical or heat stimulation after an injection of capsaicin either outside, adjacent to, or inside the receptive field (RF); any changes that occurred could not explain the hyperalgesia to mechanical or heat stimuli observed in humans.4. The depressed responsiveness ("desensitization") of both myelinated and unmyelinated nociceptive fibers in the monkey to heat and/or mechanical stimulation of the injection site after capsaicin was injected inside their RFs correlated with the analgesia observed at the capsaicin injection site in the human.5. Capsaicin, topically applied to the RF in a vehicle of dimethyl sulfoxide or alcohol, excited CMHs and AMHs and enhanced the responses of some of these fibers to heat and/or to stroking the skin. In some cases, similar results were produced by the vehicle alone. However, capsaicin and not the vehicle lowered the thresholds of some CMHs to heat. Thus the sensitization of CMHs contributes to the primary hyperalgesia known to occur within the area of skin directly exposed to topically applied capsaicin.6. We conclude that 1) the desensitization of CMHs and AMHs contributes to the cutaneous analgesia produced at the site of injection of capsaicin and 2) the prolonged neurogenic hyperalgesia to heating and mechanical stimulation of the skin surrounding an intradermal injection of capsaicin is not accounted for by the sensitization of peripheral nociceptors. It is hypothesized that the sensitized neurons contributing to neurogenic hyperalgesia are located in the CNS.