Taylor B K, Peterson M A, Basbaum A I
W. M. Keck Foundation Center for Integrative Neuroscience, University of California at San Francisco 94143, USA.
J Neurosci. 1995 Nov;15(11):7575-84. doi: 10.1523/JNEUROSCI.15-11-07575.1995.
Hindpaw injection of formalin produces acute (Phase 1) and persistent (Phase 2) nociceptive behaviors. This model has provided critical evidence supporting a contribution of central sensitization (hyperexcitability of spinal neurons) to the expression of persistent pain. Here, we evaluated the contribution of ongoing peripheral nerve inputs to Phase 2 pain responses. In addition to pain behavior (flinching), we measured formalin-evoked increases in arterial pressure and heart rate; these cardiovascular responses were also biphasic in nature. The arterial pressure response correlated highly with behavior, and was dependent on formalin concentration (0.625-5.0%), indicating that it was largely driven by noxious input. Lightly anesthetized (0.7% halothane) rats exhibited robust increases in blood pressure in the absence of pain behavior, indicating cardiovascular responses did not reflect somatomotor-cardiovascular coupling. Animals obtained from Charles River exhibited slightly larger Phase 2 flinching and heart rate responses compared to those obtained from Bantin and Kingman, suggesting cardiovascular-related pain responses can vary with the source of animal. We next evaluated the contribution of ongoing peripheral nerve activity to the expression of the Phase 2 pressor, tachycardia, and flinch responses. After Phase 1 subsided, but before Phase 2 began, we locally anesthetized the ipsilateral or contralateral (control) hindpaw with a hydrophilic lidocaine derivative, QX-314 (2%). Intraplantar QX-314 blocked Phase 2 pressor, tachycardia and behavioral responses only when injected into the paw that received formalin (2.5% or 10.0%). We conclude that persistent ongoing activity in peripheral afferent fibers during Phase 2 is required for the persistent pain evoked by formalin.
后爪注射福尔马林会产生急性（第1阶段）和持续性（第2阶段）伤害性反应。该模型提供了关键证据，支持中枢敏化（脊髓神经元的过度兴奋）对持续性疼痛表达的作用。在此，我们评估了持续的外周神经输入对第2阶段疼痛反应的作用。除了疼痛行为（退缩）外，我们还测量了福尔马林诱发的动脉血压和心率升高；这些心血管反应本质上也是双相的。动脉血压反应与行为高度相关，并且依赖于福尔马林浓度（0.625 - 5.0%），表明它在很大程度上是由伤害性输入驱动的。轻度麻醉（0.7%氟烷）的大鼠在没有疼痛行为的情况下血压显著升高，表明心血管反应并不反映躯体运动 - 心血管耦合。与从班廷和金曼公司获得的动物相比，从查尔斯河公司获得的动物表现出稍大的第2阶段退缩和心率反应，表明与心血管相关的疼痛反应可能因动物来源而异。接下来，我们评估了持续的外周神经活动对第2阶段升压、心动过速和退缩反应表达的作用。在第1阶段消退后，但在第2阶段开始前，我们用亲水性利多卡因衍生物QX - 314（2%）对同侧或对侧（对照）后爪进行局部麻醉。足底注射QX - 314仅在注射到接受福尔马林（2.5%或10.0%）的爪子时才会阻断第2阶段的升压、心动过速和行为反应。我们得出结论，第2阶段外周传入纤维的持续活动是福尔马林诱发持续性疼痛所必需的。
