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减少病理性感觉神经节中的交感神经芽生:利多卡因治疗神经性疼痛的新机制。

Decreasing sympathetic sprouting in pathologic sensory ganglia: a new mechanism for treating neuropathic pain using lidocaine.

作者信息

Zhang Jun-Ming, Li Huiqing, Munir Muhammad A

机构信息

Department of Anesthesiology, University of Arkansas for Medical Sciences, 4301 W. Markham St., #515, Little Rock, AR 72205, USA.

出版信息

Pain. 2004 May;109(1-2):143-9. doi: 10.1016/j.pain.2004.01.033.

DOI:10.1016/j.pain.2004.01.033
PMID:15082136
Abstract

Lidocaine brings relief to those suffering from certain neuropathic pain syndromes in humans and in animal models. Evidence suggests that some neuropathic pain behaviors are closely associated with extensive sprouting of noradrenergic sympathetic fibers in the dorsal root ganglia (DRG). Using immunohistochemistry, we examined lidocaine's effects on abnormal sprouting of sympathetic fibers in two animal models: rats with unilateral spinal nerve ligation (SNL) and rats with complete sciatic nerve transection (CSNT). For the first time, we have demonstrated that systemic lidocaine beginning at the time of surgery via an implanted osmotic pump remarkably reduces sympathetic sprouting (2-3 fold) (e.g. the density of sympathetic fibers and the number of DRG neurons surrounded by sympathetic fibers) in axotomized DRGs in SNL rats. The effects of systemic lidocaine lasted more than 7 days after the termination of lidocaine administration. Similar results were obtained after topical application of lidocaine to the nerve trunk to block abnormal discharges originating in the neuroma in CSNT rats. Results strongly suggest that sympathetic sprouting in pathologic DRG may be associated with abnormal spontaneous activity originating in the DRG or the injured axons (e.g. neuroma). This finding provides new insight into the mechanisms underlying sympathetic sprouting and increases our current understanding of the prolonged therapeutic effects of lidocaine on neuropathic pain syndromes.

摘要

利多卡因能缓解人类和动物模型中某些神经性疼痛综合征患者的疼痛。有证据表明,一些神经性疼痛行为与背根神经节(DRG)中去甲肾上腺素能交感神经纤维的广泛发芽密切相关。我们使用免疫组织化学方法,在两种动物模型中研究了利多卡因对交感神经纤维异常发芽的影响:单侧脊神经结扎(SNL)大鼠和坐骨神经完全横断(CSNT)大鼠。我们首次证明,在手术时通过植入的渗透泵开始全身给予利多卡因,可显著减少SNL大鼠轴突切断的DRG中交感神经发芽(2 - 3倍)(例如交感神经纤维的密度以及被交感神经纤维包围的DRG神经元数量)。在利多卡因给药终止后,全身利多卡因的作用持续超过7天。在CSNT大鼠的神经干局部应用利多卡因以阻断神经瘤产生的异常放电后,也获得了类似结果。结果强烈表明,病理性DRG中的交感神经发芽可能与DRG或受损轴突(如神经瘤)产生的异常自发活动有关。这一发现为交感神经发芽的潜在机制提供了新的见解,并加深了我们目前对利多卡因对神经性疼痛综合征的长期治疗效果的理解。

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