Centre for Research on Chronic Pain and Inflammatory Diseases, Murdoch University, Perth, Western Australia.
Department of Anesthesia, Faculty of Dentistry, and The Alan Edwards Centre for Research on Pain, McGill University, Montréal, Quebec, Canada.
J Pain. 2014 Feb;15(2):188-96. doi: 10.1016/j.jpain.2013.10.010. Epub 2013 Nov 7.
α1-Adrenoceptor expression on nociceptors may play an important role in sympathetic-sensory coupling in certain neuropathic pain syndromes. The aim of this study was to determine whether α1-adrenoceptor expression was upregulated on surviving peptidergic, nonpeptidergic, and myelinated nerve fiber populations in the skin after chronic constriction injury of the sciatic nerve in rats. Seven days after surgery, α1-adrenoceptor expression was upregulated in the epidermis and on dermal nerve fibers in plantar skin ipsilateral to the injury but not around blood vessels. This α1-adrenoceptor upregulation in the plantar skin was observed on all nerve fiber populations examined. However, α1-adrenoceptor expression was unaltered in the dorsal hind paw skin after the injury. The increased expression of α1-adrenoceptors on cutaneous nociceptors in plantar skin after chronic constriction injury suggests that this may be a site of sensory-sympathetic coupling that increases sensitivity to adrenergic agonists after nerve injury. In addition, activation of upregulated α1-adrenoceptors in the epidermis might cause release of factors that stimulate nociceptive signaling.
Our findings indicate that peripheral nerve injury provokes upregulation of α1-adrenoceptors on surviving nociceptive afferents and epidermal cells in the skin. This might contribute to sympathetically maintained pain in conditions such as complex regional pain syndrome, painful diabetic neuropathy, and postherpetic neuralgia.
伤害感受器上的α1-肾上腺素受体表达可能在某些神经病理性疼痛综合征中的交感感觉偶联中起重要作用。本研究的目的是确定在慢性缩窄性坐骨神经损伤后的大鼠皮肤中,存活的肽能、非肽能和有髓神经纤维群体上的α1-肾上腺素受体表达是否上调。手术后 7 天,损伤侧足底皮肤的表皮和真皮神经纤维上α1-肾上腺素受体表达上调,但血管周围没有上调。在所有检查的神经纤维群体中都观察到这种足底皮肤的α1-肾上腺素受体上调。然而,损伤后,后足背部皮肤的α1-肾上腺素受体表达没有改变。慢性缩窄性损伤后,伤害感受器在足底皮肤中的α1-肾上腺素受体表达增加,表明这可能是感觉-交感偶联的部位,可增加神经损伤后对肾上腺素能激动剂的敏感性。此外,表皮中上调的α1-肾上腺素受体的激活可能导致刺激伤害性信号的因子释放。
我们的发现表明,周围神经损伤会引起皮肤中存活的伤害性传入神经和表皮细胞上α1-肾上腺素受体的上调。这可能导致在复杂区域疼痛综合征、痛性糖尿病神经病变和带状疱疹后神经痛等情况下出现交感神经维持的疼痛。