Davis K D, Treede R D, Raja S N, Meyer R A, Campbell J N
Department of Neurosurgery, Johns Hopkins University, Baltimore, MD 21205 U.S.A. Department of Anesthesiology, Johns Hopkins University, Baltimore, MD 21205 U.S.A. The Applied Physics Laboratory, Johns Hopkins University, Baltimore, MD 21205 U.S.A.
Pain. 1991 Dec;47(3):309-317. doi: 10.1016/0304-3959(91)90221-I.
Patients with reflex sympathetic dystrophy or causalgia characteristically have ongoing pain and pain to light touch (hyperalgesia). Some of these patients obtain relief of their pain following interruption of sympathetic function to the affected area and, therefore, have sympathetically maintained pain (SMP). Evidence suggests that the pain and hyperalgesia in SMP are related to activation of peripheral adrenergic receptors. We wished to determine the contribution of alpha 1- and alpha 2-adrenergic receptors in SMP and thus examined the effects of local application of adrenergic agents in patients with SMP. The alpha 2-adrenergic agonist clonidine, available as a transdermal patch, was delivered topically to the patients' hyperalgesic skin. In four patients with SMP, clonidine eliminated or substantially reduced hyperalgesia to mechanical and cold stimuli. In three of these patients the effects were confined to the skin region beneath the patch, suggesting a peripheral and not central effect. The relief of hyperalgesia was not due to a local anesthetic effect since touch thresholds were unaffected. Topical clonidine did not relieve hyperalgesia of similar severity for two other patients whose hyperalgesia and pain were unaffected by sympathetic ganglion blocks (i.e., diagnosed as having sympathetically independent pain). In two SMP patients, intradermal injection of norepinephrine or phenylephrine (a specific alpha 1-adrenergic agonist) at a site treated with clonidine evoked intense pain and rekindled the pre-clonidine hyperalgesia at that site. It is likely that clonidine locally blocks the release of norepinephrine via activation of alpha 2 receptors on the sympathetic terminals. This study suggests, therefore, that SMP is mediated via alpha 1-adrenergic receptors located in the affected tissue.
患有反射性交感神经营养不良或灼性神经痛的患者通常会持续疼痛，且对轻触敏感（痛觉过敏）。这些患者中的一些人在受影响区域的交感神经功能中断后疼痛得到缓解，因此患有交感神经维持性疼痛（SMP）。有证据表明，SMP中的疼痛和痛觉过敏与外周肾上腺素能受体的激活有关。我们希望确定α1和α2肾上腺素能受体在SMP中的作用，因此研究了在SMP患者中局部应用肾上腺素能药物的效果。α2肾上腺素能激动剂可乐定有透皮贴剂，将其局部应用于患者的痛觉过敏皮肤。在4例SMP患者中，可乐定消除或显著减轻了对机械和冷刺激的痛觉过敏。在其中3例患者中，效果局限于贴剂下方的皮肤区域，表明是外周而非中枢作用。痛觉过敏的缓解并非由于局部麻醉作用，因为触觉阈值未受影响。对于另外2例痛觉过敏和疼痛不受交感神经节阻滞影响（即诊断为交感神经独立疼痛）的患者，局部应用可乐定并未缓解类似严重程度的痛觉过敏。在2例SMP患者中，在可乐定治疗过的部位皮内注射去甲肾上腺素或苯肾上腺素（一种特异性α1肾上腺素能激动剂）引发了剧烈疼痛，并在该部位重新引发了可乐定治疗前的痛觉过敏。可乐定可能通过激活交感神经末梢上的α2受体局部阻断去甲肾上腺素的释放。因此，这项研究表明，SMP是通过位于受影响组织中的α1肾上腺素能受体介导的。
