疼痛应对策略测量工具的研究概况

摘要:

摘要 目的：探讨缝隙连接蛋白Cx43在炎性镜像痛大鼠脊髓背角的表达。方法：1、行为学研究：鞘内置管成功的雄性SD大鼠24只，随机分为3组（n＝8）。CFA模型组：于大鼠左后肢踝关节外侧皮下注射完全弗氏佐剂（CFA）50μl建立佐剂性关节炎性痛模型，鞘内注射NS 10μl；CBX处理组：皮下注射CFA50μl，鞘内注射缝隙连接阻滞剂甘珀酸（CBX）100μg（10μl）；NS对照组：皮下注射NS 50μl，鞘内注射NS 10μl。分别于CFA致炎前1d(基础值)和致炎后0.5h、1d、3d、5d、7d、10d、14d每次鞘内注射后2h测定双侧的热缩足反射潜伏期（PWTL）。2、形态学研究：雄性SD大鼠20只，随机分为4组（n＝5）：NS生理盐水组、C1d组、C3d组和C7d组。分别在CFA致炎后相应时间点取腰段脊髓行Cx43免疫组织化学染色分析，测定双侧脊髓背角积分光密度值。结果：1、单侧踝关节外侧皮下注射CFA可以在致炎后2h～7d诱导出双侧的热痛觉过敏，呈现明显的镜像痛和域外痛现象(P<0.01或0.05)，鞘内注射CBX可以在炎性痛的不同阶段逆转上述改变。2、单侧CFA致炎后，大鼠脊髓双侧Cx43的表达与对照组相比均显著增加(P<0.01或0.05)，主要集中于Ⅰ～Ⅱ层和Ⅹ层，其时程变化与行为学变化基本一致。结论：大鼠单侧CFA致炎诱导的佐剂性关节炎性痛模型，具有显著的镜像痛特征。脊髓双侧背角Cx43表达增加，鞘内应用缝隙连接阻滞剂可以逆转镜像痛现象，提示脊髓缝隙连接可能在疼痛中枢敏感化中扮演重要角色。 关键词 佐剂性关节炎；镜像痛；缝隙连接；连接蛋白43；脊髓背角；甘珀酸

Abstract:

GAP JUNCTION CONNEXIN 43 EXPRESSION AT SPINAL DORSAL HORN IN A RAT MODEL OF INFLAMMATORY MIRROR-IMAGE PAIN HOU Yong-Heng, YANG Jian-Ping, ZHANG Hui-Juan , WANG Li-Na，CHENG Hao, YAO Ming (Department of Anesthesiology, The first affiliated hospital, Soochow University, Suzhou 215006) Abstract Objective：To investigate the expression of gap junction connexin 43（Cx43）on spinal dorsal horn in a rat model of adjuvant arthritis induced mirror-image pain. Methods: 1) Animal behavior research：After lumbar intrathecal catheters were successfully implanted, 24 male rats were randomly divided into 3 groups (n=8). CFA group: Rats were given subcutaneous injection (SC) of complete Freud’s adjuvant (CFA) 50μl at outer side of left ankle joint to make adjuvant arthritis model, and then given intrathecal (IT) NS 20μl; CBX group: CFA 50μl SC and carbenoxolone (CBX) 100μg IT; NS control group: NS 50μl SC and NS 20μl IT. Bilateral paw withdrawal thermal latency (PWTL) was measured at 2h after each drug delivery in post-inoculation 2h, 1d, 3d, 5d, 7d, 10d, 14d. 2) Morphological study: 20 male rats were randomly divided into 4 groups (n=5): NS control, C1d, C3d and C7d group. Immunohistochemical analysis was respectively conducted to study the change of Cx43 expression in bilateral lumbar spinal dorsal horn at relevant time in post-inoculation. Outcomes 1) Unilateral inoculation of CFA in outer side of the rat ankle joint could induce thermal hyperalgesia in injured ipsilateral (P<0.01) and contralateral (mirror-image) side (P<0.01 or 0.05) in post-inoculation 3h~7d. Itrathecal CBX could reverse such change (P<0.01 or 0.05). 2) Compared with NS control group，the expression of Cx43 increased significantly in bilateral spinal dorsal horn after CFA inoculation (P<0.01 or 0.05 ). Conclusions: Unilateral inoculation of CFA induced adjuvant arthritis had a significant phenomenon of mirror-image pain. The increase of Cx43 expression in lumbar spinal bilateral dorsal horn of rats and the reversion effect of itrathecal CBX suggested spinal gap junction may play an important role in pain central sensitization. Key words Adjuvant arthritis rats; Mirror-image pain; Gap junctions; Connexin 43; Spinal dorsal horn; Carbenoxolone