NOCICEPTOR MODULATED CENTRAL SENSITIZATION CAUSES MECHANICAL HYPERALGESIA IN ACUTE CHEMOGENIC AND CHRONIC NEUROPATHIC PAIN
NOCICEPTOR MODULATED CENTRAL SENSITIZATION CAUSES MECHANICAL HYPERALGESIA IN ACUTE CHEMOGENIC AND CHRONIC NEUROPATHIC PAIN
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DOI：
10.1093/brain/117.3.579
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发表时间：
1994-06-01
期刊：
影响因子：
14.5
通讯作者：
WAHREN, LK
中科院分区：
文献类型：
--
作者：
KOLTZENBURG, M;TOREBJORK, HE;WAHREN, LK
刷引起的疼痛（机械性异常痛，动态机械性痛觉过敏）是神经性和炎症性疼痛状态的标志。在这里，我们研究了诱导和维持机械痛觉过敏的神经机制。这些实验的主要发现是，慢性疼痛性神经病患者和急性实验性化学性疼痛的正常受试者的刷诱发疼痛的严重程度与背景疼痛的强度相关。在9名正常受试者的实验中，局部应用芥菜油5分钟可引起强烈的灼痛感和对光机械刺激的痛觉过敏。不同的神经阻滞（通过压迫桡浅神经）表明，刷引起的疼痛是由A - β纤维传递的，这种纤维通常编码无痛的触觉，而灼痛是由c -纤维传递的。心理物理测量表明，芥菜油治疗导致伤害感受器对热的明显敏感，因此随后皮肤温度从35摄氏度到40摄氏度的无害变化导致了灼烧性背景痛的比例增加。持续灼痛强度的变化与刷引起的疼痛强度密切相关（r = 0.81）。a纤维的传导阻滞只消除了触摸引起的疼痛，而c纤维的传导阻滞立即消除了持续的和触摸引起的疼痛。对9例慢性神经痛患者（平均持续时间15年）进行持续性和刷诱发性疼痛检查。在6名患者中，A - β纤维的差异阻滞消除了触摸引起的疼痛，但当只有c -纤维传导时，持续的疼痛仍然存在。在两例患者中，通过静脉局部胍乙胍阻滞和另外两例患者中，通过局部麻醉阻滞供应症状性皮肤的神经，可以完全缓解持续疼痛和刺激引起的疼痛，这表明来自原始传入神经的输入对于维持疼痛是必要的，并且持续的疼痛不是单独由中枢机制自行延续的。定量感觉试验显示4例患者有热痛觉过敏。对于这些人来说，皮肤温度的升高会导致他们持续疼痛的分级增加，这与刷引起的疼痛水平密切相关（r = 0.94）。在其余5例患者中，没有热痛觉过敏，因此没有因皮肤温度升高而加重疼痛。然而，当背景疼痛的强度自发波动时，刷引起的疼痛的严重程度也有平行的变化（r = 0.88）。我们得出结论，在正常志愿者中，刷引起的疼痛可以通过短时间的伤害性c -纤维兴奋引起中枢神经敏化状态，作为a- β纤维介导的机械痛觉过敏的基础。这种中枢兴奋性的增加，使刷引起的疼痛得以表达，是非常具有延展性的，并且主要依赖于无髓鞘初级传入神经的持续兴奋。作为推论，我们提出这些机制可以解释慢性神经痛中持续的和刷引起的疼痛，尽管它们可能不能解释神经性疼痛状态中观察到的其他感觉异常。这可能意味着初级伤害性事件的兴奋是神经性疼痛的一个重要原因，随后负责刷子诱发疼痛的中枢机制是伤害感受器激活的正常后果。
Brush-evoked pain (mechanical allodynia, dynamic mechanical hyperalgesia) is a hallmark of neuropathic and inflammatory pain states. Here we have examined the neural mechanisms that induce and maintain this component of mechanical hyperalgesia. The principle finding of these experiments is that the severity of brush-evoked pain correlates with the intensity of background pain in patients suffering from chronic painful neuropathies and in normal subjects with acute experimental chemogenic pain.In experiments on nine normal subjects topical application of mustard oil for 5 min evoked strong burning pain and hyperalgesia to light mechanical stimuli. Differential nerve blocks (by compression of the superficial radial nerve) revealed that the brush-evoked pain was transmitted by A beta-fibres, which normally encode non-painful tactile sensations, while the burning pain was signalled by C-fibres. Psychophysical measurements showed that mustard oil treatment resulted in a pronounced sensitization of nociceptors to heat so that subsequent innocuous changes of skin temperature from 35 to 40 degrees C resulted in a proportional increase of burning background pain. Changes in the magnitude of ongoing burning pain were closely correlated (r = 0.81) to the intensity of brush-evoked pain. While conduction block of A-fibres eliminated only touch-evoked pain, blockade of C-fibre excitation instantaneously abolished both ongoing and touch-evoked pain.In nine patients with chronic neuralgia (15 years mean duration) ongoing and brush-evoked pain were examined. In six patients, differential block of A beta-fibres eliminated touch-evoked pain, but ongoing pain persisted when only C-fibres were conducting. Complete relief of both ongoing and stimulus-induced pain was obtained in two patients with intravenous regional guanethedine block and in two other individuals by local anaesthetic blocks of nerves supplying the symptomatic skin, indicating that input from primaly afferents was necessary for the maintenance of the pains and that ongoing pain was not self-perpetuated by central mechanisms alone. Quantitative sensory tests revealed heat hyperalgesia in four patients. fn those individuals, an increase of skin temperature produced a graded increase of their ongoing pain which was closely correlated (r = 0.94) with the level of brush-evoked pain. In the remaining five patients there was no heat hyperalgesia and consequently no aggravation of pain by increases of skin temperature. Nevertheless when the intensity of the background pain fluctuated spontaneously there were also parallel changes (r = 0.88) of the severity of brush-evoked pain.We conclude that in normal volunteers, brush-evoked pain can be induced by short periods of nociceptive C-fibre excitation which induces a state of central nervous sensitization as the basis of A beta-fibre-mediated mechanical hyperalgesia. This central excitability increase, which permits brush-evoked pain to be expressed, is very malleable and depends critically on the continuous excitation of unmyelinated primary afferents. As a corollary, we propose that these mechanisms could account for ongoing and brush-evoked pain in chronic neuralgia, although they probably do not explain other sensory abnormalities observed in neuropathic pain states. This could mean that an excitation of primary nociceptive afferents is an important cause of neuropathic pain and that the ensuing central mechanisms responsible for brush-evoked pain are a normal sequel of nociceptor activation.