Upregulation of α1-adrenoceptors on cutaneous nerve fibres after partial sciatic nerve ligation and in complex regional pain syndrome type II
Upregulation of α1-adrenoceptors on cutaneous nerve fibres after partial sciatic nerve ligation and in complex regional pain syndrome type II
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DOI：
10.1016/j.pain.2013.12.021
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发表时间：
2014-03-01
期刊：
影响因子：
7.4
通讯作者：
Phillips, Jacqueline K.
中科院分区：
文献类型：
--
作者：
Drummond, Peter D.;Drummond, Eleanor S.;Phillips, Jacqueline K.
在周围神经损伤后，伤害性传入获得对肾上腺素能药剂的异常兴奋性，这可能是由于这些神经纤维上的α（1）-肾上腺素受体（α（1）-AR）的表达增强。为了在本研究中对此进行研究，在涉及坐骨神经部分结扎的神经性疼痛动物模型中，使用免疫组织化学评估了皮肤和坐骨神经干中神经纤维上α（1）-AR表达的变化。此外，在外周神经损伤后发生复杂性局部疼痛综合征（CRPS）（CRPS II型）的患者的疼痛和未受影响的皮肤中检查神经纤维上的α（1）-AR表达。坐骨神经部分结扎后4天，在损伤后存活的真皮神经纤维上的α（1）-AR表达高于假手术后的真皮神经纤维。在损伤的坐骨神经、真皮神经束和乳头状真皮中的非肽能伤害性传入纤维上观察到α 1-AR表达增强。周围神经损伤后真皮神经束中α（1）-AR的表达增加也与神经丝200（有髓神经纤维的标记物）共定位。在每一个受检查的患者中，CRPS影响的皮肤中的神经纤维上的α（1）-AR表达高于同一患者或无疼痛对照的未受影响的皮肤。总之，这些发现为周围神经损伤后皮肤伤害性传入的α（1）-AR上调提供了令人信服的证据。循环或局部分泌的儿茶酚胺激活这些受体可能导致CRPS II型慢性疼痛。(C)2013年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
After peripheral nerve injury, nociceptive afferents acquire an abnormal excitability to adrenergic agents, possibly due to an enhanced expression of alpha(1)-adrenoceptors (alpha(1)-ARs) on these nerve fibres. To investigate this in the present study, changes in alpha(1)-AR expression on nerve fibres in the skin and sciatic nerve trunk were assessed using immunohistochemistry in an animal model of neuropathic pain involving partial ligation of the sciatic nerve. In addition, alpha(1)-AR expression on nerve fibres was examined in painful and unaffected skin of patients who developed complex regional pain syndrome (CRPS) after a peripheral nerve injury (CRPS type II). Four days after partial ligation of the sciatic nerve, alpha(1)-AR expression was greater on dermal nerve fibres that survived the injury than on dermal nerve fibres after sham surgery. This heightened alpha(1)-AR expression was observed on nonpeptidergic nociceptive afferents in the injured sciatic nerve, dermal nerve bundles, and the papillary dermis. Heightened expression of alpha(1)-AR in dermal nerve bundles after peripheral nerve injury also colocalized with neurofilament 200, a marker of myelinated nerve fibres. In each patient examined, alpha(1)-AR expression was greater on nerve fibres in skin affected by CRPS than in unaffected skin from the same patient or from pain-free controls. Together, these findings provide compelling evidence for an upregulation of alpha(1)-ARs on cutaneous nociceptive afferents after peripheral nerve injury. Activation of these receptors by circulating or locally secreted catecholamines might contribute to chronic pain in CRPS type II. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.