目的在炎症大鼠上研究中脑导水管周围灰质注射降钙素基因相关肽(CGRP)对痛觉的影响.方法大鼠左侧足底皮下注射0.1 mL 2%的鹿角菜碱致炎后,观察中脑导水管周围灰质(PAG)注射CGRP对伤害性热刺激和机械刺激引起的后爪缩爪反应潜伏期的影响...目的在炎症大鼠上研究中脑导水管周围灰质注射降钙素基因相关肽(CGRP)对痛觉的影响.方法大鼠左侧足底皮下注射0.1 mL 2%的鹿角菜碱致炎后,观察中脑导水管周围灰质(PAG)注射CGRP对伤害性热刺激和机械刺激引起的后爪缩爪反应潜伏期的影响.结果(1)大鼠左侧足底皮下注射0.1 mL2%的鹿角菜碱引起同侧爪体积增加,双侧后爪对热刺激引起的缩爪潜伏期和机械刺激引起的缩爪阈值缩短,尤以同侧为甚;(2)PAG注射0.26 nmol/μL和0.52 nmol/μL的CGRP能引起大鼠双侧后爪对热刺激引起的缩爪潜伏期和机械刺激引起的缩爪阈值延长,但0.13 nmol/μL的CGRP没有显著性影响.结论:PAG注射CGRP有镇痛作用.展开更多
文章研究了经典名方程氏蠲痹汤(Cheng Shi Juan Bi Tang,CSJBT)对佐剂性关节炎(adjuvant arthritis,AA)大鼠的治疗作用。实验选取SD大鼠,采用弗氏完全佐剂(complete Freund's adjuvant,CFA)建立AA大鼠模型,实验设立正常组、模型组...文章研究了经典名方程氏蠲痹汤(Cheng Shi Juan Bi Tang,CSJBT)对佐剂性关节炎(adjuvant arthritis,AA)大鼠的治疗作用。实验选取SD大鼠,采用弗氏完全佐剂(complete Freund's adjuvant,CFA)建立AA大鼠模型,实验设立正常组、模型组、雷公藤多苷(glycosides of tripterygium wilfordii,GTW)组(0.01g/kg)、CSJBT 3个剂量组(分别为2.55、5.10、10.20g/kg)共6个组,考察CSJBT给药治疗14d后,其对AA大鼠足肿胀度、脏器指数和血清免疫球蛋白水平的影响,并采用HE染色法观察AA大鼠踝关节组织的形态学变化。结果显示CSJBT可缓解AA大鼠关节肿胀,降低血清Ig G水平,改善其关节组织的病理学变化,表明CSJBT对AA大鼠具有较好的治疗作用。展开更多
目的:研究催产素在侧脑室(Lv)内对正常大鼠的镇痛作用。方法:在大鼠的Lv内分别微量注射浓度为1.25、2.5和5.0 nmol/μl催产素,采用热板和压板测痛仪分别测量大鼠在5、10、15、20、30、45和60 min 7个时间点上的后爪缩爪反应潜伏期(HWL)...目的:研究催产素在侧脑室(Lv)内对正常大鼠的镇痛作用。方法:在大鼠的Lv内分别微量注射浓度为1.25、2.5和5.0 nmol/μl催产素,采用热板和压板测痛仪分别测量大鼠在5、10、15、20、30、45和60 min 7个时间点上的后爪缩爪反应潜伏期(HWL)作为衡量大鼠痛觉的指标,并与注射生理盐水相比较,观察催产素对正常大鼠的镇痛效果。结果:注射催产素以后,大鼠的HWL与注射生理盐水相比明显延长,其中浓度为1.25nmol/μl的催产素对大鼠左爪热刺激和机械刺激HWL差异有统计学意义(P<0.05),对大鼠右爪机械刺激的HWL差异有统计学意义(P<0.01);浓度为2.5nmol/μl催产素对大鼠左、右爪热刺激、机械刺激的HWL差异有统计学意义(P<0.01);浓度为5 nmol/μl对大鼠左爪热刺激和机械刺激的HWL差异有统计学意义(P<0.01),对大鼠右爪热刺激和机械刺激差异有统计学意义(P<0.01)。不同浓度催产素在侧脑室内对正常大鼠具有镇痛作用,这种镇痛作用具有剂量依赖性,且在20 min时效果最为明显。结论:催产素在Lv内延长大鼠的HWL,即催产素在Lv内具有镇痛作用。展开更多
Neuropathic pain is of serious clinical concern and only about half of patients achieve partial relief with currently-available treatments,so it is critical to find new drugs for this condition.Recently,the cellsurfac...Neuropathic pain is of serious clinical concern and only about half of patients achieve partial relief with currently-available treatments,so it is critical to find new drugs for this condition.Recently,the cellsurface trafficking of pain-related receptors has been suggested as an important mechanism underlying persistent neuropathic pain.Here,we used the short peptide GluA_（2-3y）,which specifically inhibits the GluA2-dependent endocytosis of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors,and tested its anti-nociceptive effect in the periaqueductal grey（PAG） of intact rats and rats with neuropathic pain.Intra-PAG injection of 0.15,1.5,7.5,and 15 pmol of GluA_（2-3y） induced dose-dependent increases in hindpaw withdrawal latencies to noxious thermal and mechanical stimuli in intact rats,suggesting that GluA2 cell-surface trafficking in the PAG is involved in pain modulation.Furthermore,GluA_（2-3y） had much stronger anti-nociceptive effects in rats with neuropathic pain induced by sciatic nerve ligation.Interestingly,the intra-PAG injection of 15 pmol GluA_（2-3y） had an analgesic effect similar to 10 ug（35nmol） morphine in rats with neuropathic pain.Taken together,our results suggested that GluA2 trafficking in the PAG plays a critical role in pain modulation,and inhibiting GluA2 endocytosis with GluA_（2-3y） has potent analgesic effects in rats with neuropathic pain.These findings strongly support the recent hypothesis that targeting receptor trafficking could be a new strategy for the treatment of neuropathic pain.展开更多
文摘文章研究了经典名方程氏蠲痹汤(Cheng Shi Juan Bi Tang,CSJBT)对佐剂性关节炎(adjuvant arthritis,AA)大鼠的治疗作用。实验选取SD大鼠,采用弗氏完全佐剂(complete Freund's adjuvant,CFA)建立AA大鼠模型,实验设立正常组、模型组、雷公藤多苷(glycosides of tripterygium wilfordii,GTW)组(0.01g/kg)、CSJBT 3个剂量组(分别为2.55、5.10、10.20g/kg)共6个组,考察CSJBT给药治疗14d后,其对AA大鼠足肿胀度、脏器指数和血清免疫球蛋白水平的影响,并采用HE染色法观察AA大鼠踝关节组织的形态学变化。结果显示CSJBT可缓解AA大鼠关节肿胀,降低血清Ig G水平,改善其关节组织的病理学变化,表明CSJBT对AA大鼠具有较好的治疗作用。
基金supported by the National Natural Science Foundation of China (30670658)support from the Minzu University 985 Academic Team-building Fund (YLDX01013, 2015MDTD13C and 25C)the 111 Project of China (B08044)
文摘Neuropathic pain is of serious clinical concern and only about half of patients achieve partial relief with currently-available treatments,so it is critical to find new drugs for this condition.Recently,the cellsurface trafficking of pain-related receptors has been suggested as an important mechanism underlying persistent neuropathic pain.Here,we used the short peptide GluA_（2-3y）,which specifically inhibits the GluA2-dependent endocytosis of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors,and tested its anti-nociceptive effect in the periaqueductal grey（PAG） of intact rats and rats with neuropathic pain.Intra-PAG injection of 0.15,1.5,7.5,and 15 pmol of GluA_（2-3y） induced dose-dependent increases in hindpaw withdrawal latencies to noxious thermal and mechanical stimuli in intact rats,suggesting that GluA2 cell-surface trafficking in the PAG is involved in pain modulation.Furthermore,GluA_（2-3y） had much stronger anti-nociceptive effects in rats with neuropathic pain induced by sciatic nerve ligation.Interestingly,the intra-PAG injection of 15 pmol GluA_（2-3y） had an analgesic effect similar to 10 ug（35nmol） morphine in rats with neuropathic pain.Taken together,our results suggested that GluA2 trafficking in the PAG plays a critical role in pain modulation,and inhibiting GluA2 endocytosis with GluA_（2-3y） has potent analgesic effects in rats with neuropathic pain.These findings strongly support the recent hypothesis that targeting receptor trafficking could be a new strategy for the treatment of neuropathic pain.
