C-fiber spontaneous discharge evoked by chronic inflammation is suppressed by a long-term infusion of lidocaine yielding nanogram per milliliter plasma levels
C-fiber spontaneous discharge evoked by chronic inflammation is suppressed by a long-term infusion of lidocaine yielding nanogram per milliliter plasma levels
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DOI：
10.1016/j.pain.2008.02.018
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发表时间：
2008-06-30
期刊：
影响因子：
7.4
通讯作者：
Bennett, Gary J.
中科院分区：
文献类型：
--
作者：
Xiao, Wen Hua;Bennett, Gary J.
支配发炎组织的伤害感受器会产生异常的自发放电，这被认为至少是伴随炎症的持续自发疼痛、异常性疼痛和痛觉过敏的部分原因。最近的研究表明，慢性炎性疼痛患者可以通过透皮应用利多卡因获得镇痛效果，利多卡因的血浆浓度非常低（130-225 ng/ml）。本研究的目的是调查 7 天暴露于如此低血浆浓度的利多卡因是否对大鼠炎症诱发的自发放电有影响。后爪注射完全弗氏佐剂 (CFA) 7 天后，我们证实存在肌炎、疼痛过敏，以及支配肌肉和皮肤的 A 纤维和 C 纤维自发放电发生率显着增加。然后，我们比较了注射 CFA 的动物在注射生理盐水或利多卡因 7 天后肌肉和皮肤纤维自发放电的发生率。利多卡因输注的血浆浓度为 210 ng/ml。肌肉C纤维放电被利多卡因输注完全抑制，皮肤C纤维放电被抑制50%。利多卡因输注对肌肉或皮肤 A 纤维自发放电的发生率没有影响。利多卡因输注可减轻机械性痛觉过敏，但对机械性痛觉过敏或热痛觉过敏没有影响。我们的结论是，临床上观察到的经皮利多卡因给药产生低血浆水平的镇痛效果可能是由于药物对自发活性 C 纤维的全身作用所致。 (C) 2008 年国际疼痛研究协会。由 Elsevier B.V. 出版。保留所有权利。
Nociceptors innervating inflamed tissue acquire an abnormal spontaneous discharge that is believed to be at least part of the reason for the persistent spontaneous pain, allodynia, and hyperalgesia that accompany inflammation. Recent studies suggest that patients with chronic inflammatory pain may obtain an analgesic effect with transdermal application of lidocaine that yields very low plasma levels (130-225 ng/ml). The aim of this study was to investigate whether a 7-day exposure to such low plasma levels of lidocaine had an effect on inflammation-evoked spontaneous discharge in the rat. Seven days after a hind-paw injection of Complete Freund's Adjuvant (CFA), we confirmed the presence of myositis, pain hypersensitivity, and a significant increase in the incidence of spontaneous discharge in A-fibers and C-fibers innervating both muscle and skin. We then compared the incidence of spontaneous discharge in muscle and cutaneous fibers in CFA-injected animals treated with a 7-day infusion of saline or lidocaine. The lidocaine infusion yielded a plasma level of 210 ng/ml. The muscle C-fiber discharge was completely inhibited by the lidocaine infusion and the cutaneous C-fiber discharge was suppressed by 50%. Lidocaine infusion had no effect on the incidence of spontaneous discharge in muscle or cutaneous A-fibers. Lidocaine infusion reduced mechano-hyperalgesia but had no effect on mechano-allodynia or heat-hyperalgesia. We conclude that the analgesic effects seen clinically with transdermal lidocaine administration yielding low plasma levels may be due to a systemic drug action on spontaneously active C-fibers. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.