基于疼痛抑制行为测试的青藤碱镇痛作用

Analgesic effect of sinomenine targeting the assay of pain-depressed behaviors

目的:建立基于疼痛抑制行为的测试方法,观察青藤碱对疼痛抑制行为的改善作用。方法:应用不同预处理时间及不同浓度的乳酸腹腔注射小鼠,建立化学刺激疼痛模型,以扭体反应作为疼痛激发行为指标,同时以自主活动和筑巢为疼痛抑制行为指标。观察青藤碱对乳酸诱导的疼痛激发行为及抑制行为的改善作用,并考察其剂量依赖性和药效经时过程。另以酮洛芬作为阳性对照药,将其作用与青藤碱进行比较。结果:0.32%的乳酸且预处理时间为0 min时即能显著性激发扭体行为,维持时间<30 min。仅只有0.32%乳酸显著抑制小鼠自主活动,而0.18%与0.32%乳酸均能显著抑制筑巢行为,其中0.32%乳酸作用最为显著,作用维持时间至少60 min。青藤碱(10~30 mg/kg)能剂量依赖性抑制乳酸扭体反应,其最佳作用时间为30 min。青藤碱3 mg/kg能显著改善乳酸诱发的自主活动抑制,最佳作用时间30 min,维持时间可达90 min;而剂量10~30 mg/kg时则无明显改善作用。另外青藤碱在3~30 mg/kg范围内对正常小鼠自主活动无明显影响。青藤碱20~30 mg/kg均能改善乳酸诱发的筑巢行为抑制,最佳作用剂量为20 mg/kg,最佳作用时间为30 min。酮洛芬对乳酸诱发的疼痛激发行为及抑制行为均有改善作用,青藤碱在减轻扭体行为及改善自主活动抑制方面要弱于酮洛芬,但对筑巢抑制的恢复作用要强于酮洛芬。结论:青藤碱对疼痛诱导的激发行为和抑制行为都具有改善作用,进一步证实了青藤碱的镇痛作用,为青藤碱作为镇痛药物应用于临床提供了可靠的依据。

Objective:Basing on the establishment of the assays of pain-depressed behaviors,the beneficial effects of sinomenine on pain-depressed behaviors were observed.Methods:Different pretreatment time and different concentration of lactic acid intraperitoneal injection were manipulated to build a chemical-stimulated pain model,using writhing response as an indicator of pain-stimulated behavior,and using locomotor activity and nesting as indicators of pain-depressed behaviors.Then the analgesic effect of sinomenine on lactic acid-induced writhing response as well as lactic acid-depressed locomotor activity and nesting behavior were measured.The dose-dependent and pharmacodynamic time-dependent processes of sinomenine were investigated.Meanwhile,ketoprofen was used as a positive control drug to compare its effect with that of sinomenine.Results:0.32%lactic acid at pretreatment time of 0 min significantly stimulated writhing response and its duration was less than 30 min.Lactic acid inhibited locomotor activity and nesting behavior in mice in a concentration-dependent manner.Only 0.32%lactic acid significantly suppressed locomotor activity in mice,while 0.18%and 0.32%lactic acid both significantly suppressed the nesting behavior,and the effect of 0.32%concentration was most significant with a duration of action exceeding 60 min.Sinomenine(10-30 mg/kg)dose-dependently inhibited lactic acid-induced writhing response with the optimal action time of 30 min.For locomotor activity testing,a dose of 3 mg/kg sinomenine significantly improved lactic acid-depressed locomotor activity with an optimal time of 30 min,and the effect maintained up to 90 min.However,the dose of 10-30 mg/kg sinomenine didn′t show improvement on locomotor activity.In addition,sinomenine had no effect on the locomotor activity of normal mice within the range of 3-30 mg/kg.For nesting experiment,sinomenine(20-30 mg/kg)significantly improved lactic acid-depressed nesting behavior with the optimal effect dose of 20 mg/kg and the optimal action time of 30 min.Ketoprofen both improved the pain-stimulated behavior and depressed behaviors induced by lactic acid.As compared with ketoprofen,the effect of sinomenine was weaker than ketoprofen for relieving pain-stimulated behavior and improving depressed locomotor activity,but was stronger than ketoprofen for recovering the pain-depressed nesting behavior.Conclusion:Sinomenine can both improve pain-stimulated and pain-depressed behaviors,further confirming its analgesic effect,which provides a reliable evidence for its application as an analgesic drug in clinical practice.