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
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
基金This work was supported by the Project of Science and Technology Exploitation of Fujian ProvinceChina(No.2005D073)+3 种基金the Natural Science Foundation of Fujian ProvinceChina(No.C0410018)the Project of Science and Technology Bureau of Fujian ProvinceChina(No.2006F5046)
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.
