鞘内注射甘珀酸对佐剂性关节炎大鼠热痛阈的影响

Effects of intrathecal carbenoxolone on thermal pain threshold of complete Freund’s adjuvant arthritis rats

目的研究鞘内注射缝隙连接(GJ)阻滞剂甘珀酸(CBX)对佐剂性关节炎大鼠热痛阈的影响。方法首先研究鞘内注射CBX对正常大鼠后爪热缩足反射潜伏期(PWTL)的影响,确定其时效与量效关系。根据以上结果,另取实验大鼠随机均为五组,建立佐剂性关节炎模型,随机选择一组在致炎前0.5h鞘内注射CBX100μg进行预处理,其余四组分别以CBX25、50、100μg的剂量和NS对照在致炎后0.5h、1、3、5、7、10和14d鞘内注射,每次给药后2h测定致炎侧PWTL,并连续观测0、100和100μg预处理组PWTL在致炎1d内的变化。结果(1)CBX可以可逆性、剂量依赖性地提高正常大鼠的辐射热痛阈(P<0.05或P<0.01)。在给药后1h痛阈就显著增加,2h达到高峰,持续1～2h后逐渐消退。(2)CBX在炎性痛的不同阶段都可以逆转外周完全弗氏佐剂(CFA)诱导的辐射热痛觉过敏(P<0.05或P<0.01)。(3)致炎前使用CBX预处理可以在致炎第1天延缓痛觉过敏的出现(P<0.01)。结论CBX对大鼠佐剂性关节炎诱导的病理性疼痛具有显著的抗伤害作用,提示GJ可能参与炎性痛的发生发展过程。

Objective To investigate the effects of intrathecal carbenoxolone（CBX） ,a gap junction blocker, on thermal pain threshold of complete Freund＇ s adjuvant arthritis rats. Methods At first,the time-effect and dose-effect relationships between intrathecal CBX and paw withdrawal thermal latency（PWTL） were studied in normal rats. Then on the abasis of the above outcomes,experiment rats were randomly divided into 5 groups. Adjuvant arthritis model was produced by inoculation of complete Freud＇s adjuvant（CFA） at outer side of left ankle joint. One group of them was given intrathecal CBX 100μg at 0.5 h pre-CFA inoulation as pretreatment. Four doses of CBX（0,25,50,100 μg） were respectively administered in the other 4 groups at 0.5 h, 1,3,5,7,10 and 14 d post-CFA. PWTL was measured at 2h after each drug delivery. During the first day of inoculation,the change of PWTL was espectially continually observed. Results 1. CBX could increase the threshold of radiant heat-induced pain reversibly and dose-dependently（P〈0.05 or 0. 01）. The summit effect is at 2 nd hour. 2. CBX could reverse periphery CFA-induced thermal hyperpalgesia dose-dependently in all phrases of inflammatory pain（P〈0. 05 or 0. 01）. 3. Pretreatment of CBX could postpone the appearance of thermal hyperalgesia during the first day（P〈0.01）. Conclusion Carbonexolone,as a kind of GJ blocker,has significant antinociceptive effects on adjuvant arthritis-induced pain, which suggests gap junction may play an important role in inflammatory pain.