Peterson M A, Basbaum A I, Abbadie C, Rohde D S, McKay W R, Taylor B K
W.M. Keck Foundation Center for Integrative Neuroscience and Department of Anatomy, University of California San Francisco, 94143-0452, USA.
Brain Res. 1997 Apr 25;755(1):9-16. doi: 10.1016/s0006-8993(97)00068-1.
Intraplantar injection of dilute formalin evokes brief (Phase 1) and persistent (Phase 2) increases in primary afferent activity, pain behavior, and cardiovascular responses, and induces spinal cord Fos-like immunoreactivity (Fos-LI). Although previous studies demonstrated that the destruction of small diameter primary afferents with neonatal capsaicin treatment decrease formalin-evoked nociception, these studies only evaluated behavioral responses, and did not distinguish between Phase 1 and 2. To address these questions, we simultaneously evaluated formalin-evoked pain behavior (flinching of the afflicted paw), cardiovascular responses (heart rate and mean arterial pressure), and lumbar spinal cord Fos expression in control rats and in rats treated with capsaicin (100 mg/kg) one day postpartum. We found that neonatal capsaicin-treated rats, compared to controls, exhibited similar cardiovascular responses and slightly less flinching behavior during Phase 1. During Phase 2, however, capsaicin-treated rats exhibited 59% less flinching and 45% smaller heart rate responses. Also, in capsaicin-treated rats, we counted 59% fewer Fos-labeled neurons in the spinal cord. These results indicate that capsaicin-sensitive afferents contribute to formalin-evoked behavioral and cardiovascular responses and to spinal cord neuronal responses. The differential effect of neonatal capsaicin on nociception during Phase 1 and Phase 2 suggests that sensitization mechanisms during Phase 1 do not contribute to the magnitude of nociceptive responses during Phase 2.
足底注射稀释的福尔马林会引起初级传入神经活动、疼痛行为和心血管反应的短暂增加（第1阶段）和持续增加（第2阶段），并诱导脊髓Fos样免疫反应性（Fos-LI）。尽管先前的研究表明，用新生期辣椒素处理破坏小直径初级传入神经可减少福尔马林诱发的伤害感受，但这些研究仅评估了行为反应，并未区分第1阶段和第2阶段。为了解决这些问题，我们同时评估了对照大鼠和产后一天用辣椒素（100 mg/kg）处理的大鼠中福尔马林诱发的疼痛行为（患侧爪子退缩）、心血管反应（心率和平均动脉压）以及腰脊髓Fos表达。我们发现，与对照组相比，新生期辣椒素处理的大鼠在第1阶段表现出相似的心血管反应，且退缩行为略少。然而，在第2阶段，辣椒素处理的大鼠退缩行为减少了59%，心率反应减小了45%。此外，在辣椒素处理的大鼠中，我们在脊髓中计数到的Fos标记神经元减少了59%。这些结果表明，辣椒素敏感的传入神经参与了福尔马林诱发的行为和心血管反应以及脊髓神经元反应。新生期辣椒素对第1阶段和第2阶段伤害感受的不同影响表明，第1阶段的敏化机制对第2阶段伤害性反应的程度没有贡献。
