Pretreatment with intrathecal amitriptyline potentiates anti-hyperalgesic effects of post-injury intra-peritoneal amitriptyline following spinal nerve ligation

ABSTRACT: BACKGROUND: Amitriptyline, a tricyclic antidepressant and potent use-dependent blocker of sodium channels, has been shown to attenuate acute and chronic pain in several preclinical modes. The purpose of this study was to investigate whether intrathecal pretreatment with amitriptyline combined with post-injury intra-peritoneal amitriptyline is more effective than post-injury treatment alone on L5 spinal nerve ligation (SNL)-induced neuropathic pain. Methods: 96 adult male Sprague-Dawley rats were allocated into 4 groups: group S, Sham; group L, L5 spinal nerve Ligation with vehicle treatment; group A, SNL and post-injury intra-peritoneal (Abdominal) amitriptyline twice daily x 3 days; group P, intrathecal Pretreatment with amitriptyline, SNL and intra-peritoneal amitriptyline twice daily x 3 days. Responses to thermal and mechanical stimuli, as well as sodium channel expression in injured dorsal root ganglion (DRG) and activated glial cells in spinal dorsal horn (SDH) were measured pre-operatively and on post-operative day (POD) 4, 7, 14, 21 and 28. Results: SNL-evoked hyper-sensitivities responses to thermal and mechanical stimuli, up-regulated Nav1.3 and down-regulated Nav1.8 expression in DRG, and activated microglia and astrocytes in SDH. In group A, intra-peritoneal amitriptyline alone alleviated thermal hypersensitivity on POD7, reversed Nav1.8 and reduced activated microglia on POD14. In group P, intrathecal pretreatment with amitriptyline not only potentiated the effect of intra-peritoneal amitriptyline on thermal hypersensitivity and Nav1.8, but attenuated mechanical hypersensitivity on POD7 and reduced up-regulated Nav1.3 on POD14. Furthermore, this treatment regimen reduced astrocyte activation on POD14. Conclusions: Concomitant intrathecal pretreatment and post-injury intra-peritoneal amitriptyline was more effective than post-injury treatment alone on attenuation of behavioral hypersensitivity, decrease of activated microglia and astrocytes and dysregulated Nav1.3 and 1.8.     

柑橘精油及壳聚糖复合处理对橄榄果实采后生理和耐贮性的影响

为探究柑橘精油(0.25%、0.75%、1.5%)和壳聚糖(0.25%、0.75%、1.5%)复合处理对橄榄(Canarium album)果实采后生理和耐贮性的影响，以鲜食橄榄品种(系)‘檀香’、‘梅埔2号’为材料，对采后贮藏期间的腐烂率、褐变指数、相对电导率、呼吸强度、丙二醛含量、内源抗氧化物质谷胱甘肽含量、过氧化物酶(POD)、抗坏血酸过氧化物酶(APX)活性进行测定，筛选橄榄果实复合保鲜剂的最佳浓度组合。结果表明，与对照相比，所有柑橘精油和壳聚糖复合处理均可有效降低橄榄果实在贮藏期间腐烂率、褐变指数和丙二醛的积累，抑制呼吸作用，保持较高的内源抗氧化物质谷胱甘肽含量和POD、APX活性。因此柑橘精油及壳聚糖处理能够有效延长橄榄果实的保鲜时间，提高耐贮性，其中以1.5%柑橘精油和1.5%壳聚糖组合的保鲜效果最佳。