Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, 42 Jebongro Dong-gu, Gwangju 501-757, Republic of Korea.
Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, 42 Jebongro Dong-gu, Gwangju 501-757, Republic of Korea The Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University, Gwangju, Republic of Korea
Br J Anaesth. 2014 Jul;113(1):138-47. doi: 10.1093/bja/aet336. Epub 2013 Oct 14.
Spinal serotonin (5-HT) receptors 3 (5-HT3R) and 7 (5-HT7R) are differentially involved in facilitatory or inhibitory descending modulation, respectively. Electrophysiological studies of the spinal cord have demonstrated that 5-HT3R is involved in nociception induced by intraplantar injection of formalin, but not carrageenan. In addition, depletion of spinal serotonin has been shown to attenuate pain behaviour in the formalin test, but there have been no such reports regarding the carrageenan model. This study compared the role of 5-HT7R and the influence of descending serotonergic modulation between formalin- and carrageenan-induced inflammatory pain.
Effects of intrathecal (i.t.) AS-19 (5-HT7R agonist) and SB-269970 (5-HT3R antagonist) on flinching response in the formalin test and mechanical allodynia in the carrageenan model were evaluated in male Sprague-Dawley rats. The effect of serotonin depletion by i.t. 5,7-dihydroxytryptamine was also examined in the two models.
Intrathecal AS-19 significantly reduced the flinching responses in the formalin test (P<0.01), which was reversed by i.t. SB269970. However, neither AS-19 nor SB269970 produced a significant change in mechanical allodynia in the carrageenan model. Depletion of spinal serotonin attenuated the flinching response in phase 2 of the formalin test (P<0.01), but increased mechanical allodynia in the carrageenan model compared with controls (P<0.01).
Spinal 5-HT7R plays a significant inhibitory role in descending serotonergic modulation in pain induced by formalin but not carrageenan. Descending serotonergic modulation is differentially involved in inflammatory pain induced by formalin and carrageenan, with facilitatory and inhibitory effects, respectively.
脊髓 5-羟色胺（5-HT）受体 3（5-HT3R）和 7（5-HT7R）分别参与促进或抑制下行调制。脊髓的电生理学研究表明，5-HT3R 参与了足底注射福尔马林引起的痛觉过敏，但不参与角叉菜胶引起的痛觉过敏。此外，脊髓 5-HT 的耗竭已被证明可减轻福尔马林试验中的疼痛行为，但尚无关于角叉菜胶模型的此类报道。本研究比较了 5-HT7R 在福尔马林和角叉菜胶诱导的炎症性疼痛中的作用，以及下行 5-羟色胺能调制的影响。
在雄性 Sprague-Dawley 大鼠中，评估鞘内（i.t.）给予 AS-19（5-HT7R 激动剂）和 SB-269970（5-HT3R 拮抗剂）对福尔马林试验中退缩反应和角叉菜胶模型中机械性痛觉过敏的影响。还在两种模型中检查了 i.t.5,7-二羟基色胺对 5-羟色胺耗竭的影响。
鞘内 AS-19 显著减少了福尔马林试验中的退缩反应（P<0.01），而鞘内 SB269970 则逆转了这一反应。然而，AS-19 或 SB269970 对角叉菜胶模型中的机械性痛觉过敏均无显著变化。脊髓 5-羟色胺耗竭减少了福尔马林试验第二阶段的退缩反应（P<0.01），但与对照组相比，增加了角叉菜胶模型中的机械性痛觉过敏（P<0.01）。
脊髓 5-HT7R 在福尔马林诱导的疼痛下行 5-羟色胺能调制中发挥显著的抑制作用，但在角叉菜胶诱导的疼痛中则没有。下行 5-羟色胺能调制分别参与了福尔马林和角叉菜胶诱导的炎症性疼痛，具有促进和抑制作用。
