3种青蒿素衍生物对神经病理性疼痛小鼠痛共情绪障碍干预效果的比较

Application of three artemisinin derivatives in neuropathic pain:evaluating co-curation of nociceptive and emotional syndromes in spinal cord ligation mice

该研究以机械痛、焦虑及抑郁为指标,在脊神经结扎小鼠（spinal cord ligation,SNL）中,评价并比较双氢青蒿素（DHA）、青蒿琥酯（ART）及蒿甲醚（ARTN）3种青蒿素衍生物对神经病理性疼痛（neuropathic pain,NP）的干预效果。实验以临床等效剂量的NP一线药物普瑞巴林（PGB）25 mg·kg^-1、阿米替林（ARP）20 mg·kg^-1为阳性对照;在造模后4~17 d,以40 mg·kg^-1DHA,ART,ARTN灌胃给药;以Von Frey法,评价小鼠机械痛;以旷场、悬尾实验,评价小鼠焦虑及抑郁行为。结果显示,在SNL模型中,PGB具有迅速镇痛、部分缓解的特点,但对痛诱发焦虑及抑郁无效;而ARP在镇痛方面起效缓慢且仅部分缓解,而对焦虑的缓解不稳定,但抗抑郁效果好。在给药7~14 d,3种青蒿素衍生物逐渐显现镇痛,抗焦虑及抑郁效果。给药14 d,在机械痛方面,灌胃后1.5 h,3种青蒿素衍生物组均恢复到假手术状态;在3 h,DHA及ART组小鼠机械痛阈值较1.5h无显著变化,而ARTN组机械痛阈值较1.5 h显著下降;在24 h,3组青蒿素衍生物小鼠机械痛阈值均较1.5 h显著降低,但高于PGB组。在焦虑及抑郁方面,DHA,ART组恢复到假手术组水平,显著优于ARTN组。该研究发现3种青蒿衍生物对神经病理性疼痛小鼠痛共情绪障碍均有抑制作用。其中,DHA和ART的镇痛持续时间、抗焦虑和抑郁作用显著优于ARTN。

In this study,on aspects of the nociceptive,anxiety and depressive syndromes in neuropathic pain（NP）,the effects of dihydroartemisinine（DHA）,artesunate（ART） and artemether（ARTN）（40 mg·kg^-1） were analyzed in the spinal cord ligation（SNL） mice. Clinical equivalent dose of the first-line drug for NP,pregabalin（PGB,25 mg·kg^-1） and amitriptyline（ARP,20 mg·kg^-1）,were used as positive controls. General,from day 7 to 14,significant remissions of the nociceptive,anxiety and depressive behaviors were achieved by DHA,ART and ARTN separately. Moreover,on day 14,on aspects of the nociceptive behaviors,analyzed1. 5 h after the gavage administration,no significant difference between the shamed mice and mice administrated with DHA,ART and ARTN was detected; analyzed 3 h after the gavage,significant decreases of pain thresholds in ARTN,but not in DHA nor ART group,were detected as compared with thresholds measured 1. 5 h; analyzed 24 h after gavage,pain thresholds in DHA,ART and ARTN were still higher than PGB,in spite of the significant decreases as compared to Sham group. On aspects of the anxiety and depressive behaviors,no significant difference was detected between the shamed mice and mice administrated with DHA nor ART. However,differences still remained between the shamed ones and ones administrated with ARTN. Preliminarily,the effects of DHA,ART and ARTN were consolidated in SNL mice. On aspects of the duration of analgesic effects and the control of negative emotion,ART and ARTN were proven more favorable than ARTN.