Drummond Eleanor S, Maker Garth, Birklein Frank, Finch Philip M, Drummond Peter D
Centre for Research on Chronic Pain and Inflammatory Diseases, Murdoch University, Perth, Western Australia.
Department of Neurology, University Medical Center, Mainz, Germany.
Eur J Pain. 2016 Jul;20(6):926-35. doi: 10.1002/ejp.817. Epub 2015 Nov 16.
The sympathetic nervous system may play an important role in certain forms of chronic pain. The main aim of this study was to determine whether functional blockade of α1 -adrenoceptors would alter sensitivity to cutaneous stimulation in patients with complex regional pain syndrome (CRPS).
In an initial study, high-performance liquid chromatography-mass spectrometry of intradermal interstitial fluid collected from the forearms of three healthy individuals established that the α1 -adrenoceptor antagonist prazosin penetrated the skin barrier when mixed in Lipoderm(®) cream base. Next, we found that application of this cream to the forearm of 10 healthy participants attenuated axon reflex vasodilatation to the iontophoresis of phenylephrine, demonstrating functional blockade of α1 -adrenoceptors. Subsequently, effects of the cream on sensitivity to mechanical and thermal stimulation were investigated in 14 healthy participants and 19 patients with CRPS (eight with an apparent adrenergic component of pain). Both in patients and controls, topical application of the prazosin cream increased sensitivity to skin cooling but reduced sensations evoked by gentle brushing. In addition, hyperalgesia to sharp stimulation was lower at the prazosin- than vehicle-treated site in the CRPS-affected limb, and allodynia to brushing was lower at the prazosin-treated than vehicle-treated site in patients with an adrenergic component of pain.
Prazosin cream inhibited adrenergic axon reflex vasodilatation in healthy volunteers, and also inhibited dynamic allodynia and punctate hyperalgesia in the CRPS-affected limb of some patients. Further studies are required to assess the potential benefits of topically applied prazosin for CRPS.
交感神经系统可能在某些形式的慢性疼痛中起重要作用。本研究的主要目的是确定α1肾上腺素能受体的功能阻断是否会改变复杂区域疼痛综合征（CRPS）患者对皮肤刺激的敏感性。
在一项初步研究中，通过高效液相色谱-质谱法对从三名健康个体前臂采集的皮内组织间液进行分析，结果表明，α1肾上腺素能受体拮抗剂哌唑嗪与Lipoderm®乳膏基质混合后能够穿透皮肤屏障。接下来，我们发现将这种乳膏应用于10名健康参与者的前臂，可减弱对苯肾上腺素离子导入的轴突反射性血管舒张，表明α1肾上腺素能受体被功能性阻断。随后，在14名健康参与者和19名CRPS患者（其中8名患者的疼痛明显有肾上腺素能成分）中研究了该乳膏对机械和热刺激敏感性的影响。在患者和对照组中，局部应用哌唑嗪乳膏均增加了对皮肤冷却的敏感性，但减少了轻刷引起的感觉。此外，在CRPS受累肢体中，与使用赋形剂治疗的部位相比，使用哌唑嗪治疗的部位对尖锐刺激的痛觉过敏较低；在有肾上腺素能疼痛成分的患者中，与使用赋形剂治疗的部位相比，使用哌唑嗪治疗的部位对轻刷的异常性疼痛较低。
哌唑嗪乳膏在健康志愿者中抑制了肾上腺素能轴突反射性血管舒张，并且在一些患者的CRPS受累肢体中也抑制了动态异常性疼痛和点状痛觉过敏。需要进一步研究以评估局部应用哌唑嗪治疗CRPS的潜在益处。
