Multiple phases of relief from experimental mechanical allodynia by systemic lidocaine: responses to early and late infusions
Multiple phases of relief from experimental mechanical allodynia by systemic lidocaine: responses to early and late infusions
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DOI：
10.1016/s0304-3959(02)00350-0
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发表时间：
2003-05-01
期刊：
影响因子：
7.4
通讯作者：
Strichartz, GR
中科院分区：
文献类型：
--
作者：
Araujo, MC;Sinnott, CJ;Strichartz, GR
全身性利多卡因可缓解神经损伤后产生的各种形式的神经病理性疼痛。机械性异常性疼痛，定义为大鼠脊神经结扎（L5-L 6）后爪缩回阈值力的显著下降，可以通过以低至1-2 μ g/ml的恒定血浆浓度输注一次30分钟的利多卡因来逆转，当大鼠在数天和数周后进行测试时，该作用仍然存在。在这项研究中，我们解决了详细的时间过程中逆转同侧和对侧异常性疼痛的大鼠脊髓神经结扎单全身输注利多卡因，4 μ g/ml，结扎后2天（POD 2）或结扎后7天（POD 7）。在经历假手术或脊神经结扎以产生异常性疼痛后，检查雄性Sprague-Dawley大鼠21天，所述异常性疼痛通过仅产生缩爪所需的足底后爪处的von Frey毛的较低力（缩爪阈值，PWT）来定量。实验分为6组：L2组于术后第2天（POD 2）、L7组于术后第7天（POD 7）、S2组于术后第2天（POD 2）、K组于术后第7天（POD 7）、S2组于术后第2天（POD 2）、K组于术后第7天（POD 7）分别给予利多卡因和生理盐水。在单次30 min利多卡因输注的最后5 min;开始输注后30、60、90、120、240和360 min以及24、48和72 h，然后每1-3天测量一次PWT，直至21天。在L2和U组中，同侧缓解的三个明显的连续阶段是：（1）在输注期间PWT急性升高，在输注后30-60 min内恢复到输注前异常性疼痛水平;（2）在接下来的360 min内PWT第二次短暂升高;（3）PWT在输注后24 h内缓慢升高，并持续21 d。一个显着的，虽然较弱的对侧异常性疼痛发展更慢（> POD 8）比同侧的条件，并可以延迟超过2周的利多卡因输注POD 2，但只有1周的POD 7相同的治疗。假手术动物均未出现任何异常性疼痛体征，并且在结扎的异常性疼痛大鼠中，没有盐水输注升高PWT。这些不同阶段的结果意味着单次输注利多卡因后异常性疼痛的急性缓解和持续缓解之间存在机制差异，并可能为研究早期而非晚期治疗干预的优势提供实验范例。(C)2002年国际疼痛研究协会。出版社：Elsevier Science B. V. All Fights Reserved
Systemic lidocaine can relieve various forms of neuropathic pain that develop after nerve injury. Mechanical allodynia, defined by a significant drop in paw withdrawal threshold force following spinal nerve ligation (L5-L6) in rats, can be reversed by one 30 min lidocaine infusion at a constant plasma concentration as low as 1-2 mug/ml, an effect that is still present when the rats are tested days and weeks afterwards. In this study, we resolved the detailed time course of reversal of ipsilateral and contralateral allodynia in rats with spinal nerve ligation by a single systemic infusion of lidocaine, to 4 mug/ml, given either 2 days after ligation (POD2) or 7 days after ligation (POD7). Male Sprague-Dawley rats were examined for 21 days after undergoing sham operation or spinal nerve ligation to produce allodynia, which was quantified by a lower force of von Frey hairs at the plantar hind paw just required to produce paw withdrawal (paw withdrawal threshold, PWT). Six experimental protocols were followed: rats were infused with lidocaine on POD2 (L2) or on POD7 (L7), or with saline on POD2 (S2) or on POD7 (K), and sham operated rats were infused with lidocaine on POD2 or on POD7. PWTs were measured during the last 5 min of a single 30 min lidocaine infusion; at 30, 60, 90, 120, 240 and 360 min, and 24, 48 and 72 h after beginning infusion, and then every 1-3 days up to 21 days. Three distinct sequential phases of ipsilateral relief were apparent in both L2 and U groups: (1) an acute elevation of PWT during the infusion, returning to the pre-infusion allodynic level within 30-60 min after infusion; (2) a second, transient elevation of PWT within the next 360 min; (3) a sustained elevation of PWT developing slowly over 24 h after infusion and maintained over the next 21 days. A significant, although weaker contralateral allodynia developed more slowly (>POD8) than the ipsilateral condition, and could be delayed for more than 2 weeks by lidocaine infusion on POD2 but for only 1 week by the same treatment on POD7. None of the sham operated animals had any allodynic signs and no saline infusions elevated PWT in ligated, allodynic rats. These results of separate phases imply that there are mechanistic differences between the acute relief and the sustained relief of allodynia after a single infusion of lidocaine, and may present an experimental paradigm for investigating the advantages of earlier rather than late therapeutic intervention. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All fights reserved.