Puig S, Sorkin L S
Department of Anesthesiology, University of California at San Diego, La Jolla, CA 92093-0818 USA.
Pain. 1996 Feb;64(2):345-355. doi: 10.1016/0304-3959(95)00121-2.
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 microliters) 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 micrograms/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.
将福尔马林皮下注射到爪部是一种常用的疼痛测定方法；它会引发一个最初的舔舐和退缩期，接着是一段静止期，最后是第二个强烈且持久的舔舐和退缩期。人们认为突出的第二阶段反映了中枢（脊髓）易化作用的发展。这一结论基于这样的假设：福尔马林会引发细传入纤维的初始活动爆发，随后C纤维出现持续的低水平活动。然而，尚未发表详细报告来证实这一关键假设。因此，我们在巴比妥类麻醉的大鼠中，通过传导速度和模式鉴定，对单个腓肠神经纤维进行了原位记录。在将福尔马林（2.5%，50微升）注射到它们的感受野后，Aβ和Aδ纤维以及高阈值C伤害性传入纤维中第一阶段的活动很突出。在有毛皮肤感受野的Aδ纤维和所有机械敏感的C纤维中观察到了第二阶段的活动。这些纤维中第二阶段的平均活动量是第一阶段所达到量的1/2 - 2/3。机械不敏感纤维以及感受野中心在注射区域之外的Aδ和C纤维在注射后15分钟或更久开始放电，并且会促成第二阶段而非第一阶段的行为活动。在第二阶段静脉输注低剂量利多卡因，使血浆浓度达到3.6 - 7.9微克/毫升，以剂量相关的方式阻断了初级传入纤维中福尔马林诱发的活动，而没有阻断电刺激或机械刺激诱发的活动。有效的血浆剂量与那些被发现可缓解神经性疼痛的剂量相当。这些数据表明，福尔马林试验中的第二阶段与持续的传入输入比之前认为的更为密切相关。
