Sympathetic fibre sprouting in the skin contributes to pain-related behaviour in spared nerve injury and cuff models of neuropathic pain.
Sympathetic fibre sprouting in the skin contributes to pain-related behaviour in spared nerve injury and cuff models of neuropathic pain.
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DOI：
10.1186/s12990-015-0062-x
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发表时间：
2015-09-17
期刊：
影响因子：
3.3
通讯作者：
Ribeiro-da-Silva A
中科院分区：
文献类型：
--
作者：
Nascimento FP;Magnussen C;Yousefpour N;Ribeiro-da-Silva A
坐骨区域的袖带和幸免神经损伤（SNI）被广泛用于模拟神经性疼痛。因为伤害性信息首先在皮肤中被检测到，所以了解周围神经支配的改变如何在每个模型中促进疼痛是很重要的。在16周的雄性大鼠中，使用免疫组织化学标记袖带和SNI后皮肤感觉和自主神经支配的变化有髓鞘（神经丝200阳性- NF200+）和肽能（降钙素基因相关肽阳性- CGRP+）初级传入神经和交感神经纤维（多巴胺β-羟化酶阳性- dbh +）袖带和SNI引起足底后爪皮肤NF200和CGRP纤维的早期丢失和后来的再神经支配。在两种模型中，DBH+纤维在损伤后4周和6周在足底皮肤上真皮层萌发。尽管有这些相似之处，但每个模型的行为疼痛测量值有显著差异。使用胍乙啶进行交感神经切除术可显著缓解袖带后6周的机械异常性痛，此时观察到交感神经芽的峰值，但在2周纤维缺失时没有效果。在SNI动物中，2周和6周时，胍乙啶显著改善了侧足的机械异常性痛，6周时，胍乙啶减轻了与异位交感纤维外观大致相似的冷痛觉过敏的发生。交感神经纤维在2周或6周时没有长出背根神经节，表明它们在这两种模型中对疼痛行为不重要。皮肤交感神经支配的改变是导致袖带和SNI型神经性疼痛模型疼痛的重要机制。
Cuff and spared nerve injury (SNI) in the sciatic territory are widely used to model neuropathic pain. Because nociceptive information is first detected in skin, it is important to understand how alterations in peripheral innervation contribute to pain in each model. Over 16 weeks in male rats, changes in sensory and autonomic innervation of the skin were described after cuff and SNI using immunohistochemistry to label myelinated (neurofilament 200 positive—NF200+) and peptidergic (calcitonin gene-related peptide positive—CGRP+) primary afferents and sympathetic fibres (dopamine β-hydroxylase positive—DBH+) Cuff and SNI caused an early loss and later reinnervation of NF200 and CGRP fibres in the plantar hind paw skin. In both models, DBH+ fibres sprouted into the upper dermis of the plantar skin 4 and 6 weeks after injury. Despite these similarities, behavioural pain measures were significantly different in each model. Sympathectomy using guanethidine significantly alleviated mechanical allodynia 6 weeks after cuff, when peak sympathetic sprouting was observed, having no effect at 2 weeks, when fibres were absent. In SNI animals, mechanical allodynia in the lateral paw was significantly improved by guanethidine at 2 and 6 weeks, and the development of cold hyperalgesia, which roughly paralleled the appearance of ectopic sympathetic fibres, was alleviated by guanethidine at 6 weeks. Sympathetic fibres did not sprout into the dorsal root ganglia at 2 or 6 weeks, indicating their unimportance to pain behaviour in these two models. Alterations in sympathetic innervation in the skin represents an important mechanism that contributes to pain in cuff and SNI models of neuropathic pain.