Formalin-evoked activity in identified primary afferent fibers: Systemic lidocaine suppresses phase-2 activity

Formalin-evoked activity in identified primary afferent fibers: Systemic lidocaine suppresses phase-2 activity
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DOI:
10.1016/0304-3959(95)00121-2
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发表时间:
1996-02-01
期刊:
影响因子:
7.4
通讯作者:
Sorkin, LS
Sorkin, LS
中科院分区:
医学1区
文献类型:
--
作者:
Puig, S;Sorkin, LS

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福尔马林皮下注射到爪子中是一种常用的疼痛测定法;它引起最初的舔和退缩期,随后是一段静止期,最后是第二段强烈和延长的舔和退缩期。突出的第二阶段被认为反映了中枢(脊髓)易化的发展。这一结论是基于这样的假设,即福尔马林引起了一个最初的爆发活动的细传入纤维,随后在C纤维的长期低水平的活动。证实这一基本假设的详细报告尚未发表。因此,我们在巴比妥酸盐麻醉大鼠的单个腓肠神经纤维上原位记录了它们的传导速度和形式,(2.5%,50 μ l)注射到它们的感受野中,在A β和A δ纤维以及高阈值C伤害性传入纤维中,在A δ纤维中观察到2相活性,其感受野在有毛皮肤和所有机械敏感的C纤维中。这些纤维中的平均2相活性是1相中达到的量级的1/2-2/3。机械不敏感的纤维和A δ和C纤维的感受野中心的注射区以外的注射后15分钟或更长时间开始发射,将有助于阶段2,但不是阶段1,行为活动。静脉输注低剂量利多卡因,在第2阶段期间给予血浆水平为3.6-7.9 μ g/ml,以剂量相关方式阻断初级传入纤维中福尔马林诱发的活动,而不阻断电或机械诱发的活动。有效的血浆剂量与缓解神经性疼痛的剂量相当。这些数据表明,在福尔马林试验的第二阶段是更密切相关的持续传入输入比以前认为的。
Formalin injected subcutaneously into the paw is a frequently used pain assay; it evokes an initial period of licking and flinching followed by a period of quiescence and last by a second period of intense and protracted licking and flinching. The prominent second phase is believed to reflect the development of a central (spinal cord) facilitation. This conclusion is based on the assumption that formalin evokes an initial burst of activity in fine afferent fibers, followed by prolonged low levels of activity in C fibers. Detailed reports substantiating this essential assumption have not been published, Thus, we recorded in situ from single sural nerve fibers, identified by their conduction velocity and modality, in the barbiturate anesthetized rat, Following formalin (2.5%, 50 mu l) injection into their receptive fields, phase-1 activity was prominent in A beta and A delta fibers as well as in high-threshold C nociceptive afferent fibers, Phase-2 activity was observed in A delta fibers with receptive fields in hairy skin and in all mechanically sensitive C fibers. Mean phase-2 activity in these fibers was 1/2-2/3 of the magnitude achieved in phase 1. Mechanically insensitive fibers and A delta and C fibers with receptive field centers outside of the injection zone began firing 15 min or more post-injection and would contribute to phase-2 but not phase-1, behavioral activity. Intravenous infusion of low doses of lidocaine yielding plasma levels of 3.6-7.9 mu g/ml administered during phase 2 blocked formalin-evoked activity in primary afferent fibers in a dose-related fashion without blocking either electrically or mechanically evoked activity. Effective plasma doses were comparable to those found to relieve neuropathic pain. These data indicate that phase 2 in the formalin test is more closely related to ongoing afferent input than had previously been thought.