BACKGROUND： Following morphine withdrawal, anxiety is associated with abnormal norepinephrine content change. However, increasing blood lactic acid content can induce anxiety or panic in patients with anxiety disorde...BACKGROUND： Following morphine withdrawal, anxiety is associated with abnormal norepinephrine content change. However, increasing blood lactic acid content can induce anxiety or panic in patients with anxiety disorder or endogenous opioid peptide functional disorder. OBJECTIVE： This study was designed to observe the effects of electro-acupuncture, at the ＂Sanyinjiao＂ point （SP 6）, on brain tissue norepinephrine and blood lactic acid content in anxiety-model mice after morphine withdrawal. DESIGN： A randomized controlled animal experiment. SETTING： This study was performed in the Laboratory of Acupuncture, Electro-acupuncture ＆ Tuina College, Chengdu University of Traditional Chinese Medicine, from June to September 2001. MATERIALS： A total of 50 healthy Kunming male mice were provided by the Laboratory Animal Center of Chengdu University of Traditional Chinese Medicine. The protocol was performed in accordance with ethical guidelines stated in the Guide for the use and care of laboratory animals, approved by the Committee on the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources Commission on Life Sciences, National Research Council, China （1985）. Experimental reagents and equipment used were as follows： morphine hydrochloride （Lot No. 930503, Shenyang No.1 Pharmaceutical Factory, China）, norepinephrine （Sigma Chemical Company, USA）, fluorospectrophotometer （RF-510, Shimadzu Corporation, Japan）, Han electro-acupuncture apparatus （WQ 1002, No. zun （91）-227270-588, Beijing Anlong Photoelectricity-Technique Company, China）, and T-maze （self-made）. METHODS： A total of 50 mice were randomly divided into 5 groups, with 10 mice in each group： blank control, T-maze, model, model ＋ electro-acupuncture, and electro-acupuncture groups. Establishment of anxiety model after morphine withdrawal： the mouse hot plate assay was used to detect the activity of morphine. The median effective dose of morphine, 2.95 mg/kg, was defined as the base. Mice were subcutaneously administered morphine, 3 times a day, for 4 days successively （initially 2.95 mg/kg, then increased day by day, as described below）. Interventions： In the model ＋ electro-acupuncture group, after model induction, mice were subjected electro-acupuncture at bilateral ＂Sanyinjiao＂ （SP6） points using a Han electro-acupuncture apparatus with sparse-dense waves and frequency of 2-100 Hz, once a day, for 6 days. In the model group, after anxiety-model induction, mice were subjected to fixation as same as model ＋ electro-acupuncture group within 6 days of model induction. In the electro-acupuncture group, the anxiety model was not induced and mice were subjected to fixation, electro-acupuncture and the T-maze test. In the T-maze group, the anxiety model was not induced and mice were subjected to fixation. The T-maze test was performed in the 4 groups after experiment. In the blank control group, the anxiety model was not induced and mice were subjected to fixation only. MAIN OUTCOME MEASURES： Brain tissue norepinephrine content of morphine-withdrawal anxiety mice was detected by fluorospectrophotometry after 6 days of electro-acupuncture. Blood lactic acid content was detected by visible spectrophotometry. RESULTS： A total of 50 mice were included in the final analysis. Brain norepinephrine content was significantly greater in the model group compared to the T-maze, blank control, electro-acupuncture and model ＋ electro-acupuncture groups, （P 〈 0.05-0.01）. Brain norepinephrine content was similar between the model ＋ electro-acupuncture and the blank control groups （P 〉 0.05）. There was no significant difference in blood lactic acid content among the groups （P 〉 0.05）. CONCLUSION： Electro-acupuncture lowers brain norepinephrine content but does not influence peripheral blood lactic acid content in morphine-withdrawn, anxiety-modeled mice. These results demonstrate that anxiety-inhibiting effects of electro-acupuncture, after morphine withdrawal, might be related to regulation of norepinephrine release.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the Grant from Administration of Traditional Chinese Medicine of Sichuan Province, No. 2000-48
文摘BACKGROUND： Following morphine withdrawal, anxiety is associated with abnormal norepinephrine content change. However, increasing blood lactic acid content can induce anxiety or panic in patients with anxiety disorder or endogenous opioid peptide functional disorder. OBJECTIVE： This study was designed to observe the effects of electro-acupuncture, at the ＂Sanyinjiao＂ point （SP 6）, on brain tissue norepinephrine and blood lactic acid content in anxiety-model mice after morphine withdrawal. DESIGN： A randomized controlled animal experiment. SETTING： This study was performed in the Laboratory of Acupuncture, Electro-acupuncture ＆ Tuina College, Chengdu University of Traditional Chinese Medicine, from June to September 2001. MATERIALS： A total of 50 healthy Kunming male mice were provided by the Laboratory Animal Center of Chengdu University of Traditional Chinese Medicine. The protocol was performed in accordance with ethical guidelines stated in the Guide for the use and care of laboratory animals, approved by the Committee on the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources Commission on Life Sciences, National Research Council, China （1985）. Experimental reagents and equipment used were as follows： morphine hydrochloride （Lot No. 930503, Shenyang No.1 Pharmaceutical Factory, China）, norepinephrine （Sigma Chemical Company, USA）, fluorospectrophotometer （RF-510, Shimadzu Corporation, Japan）, Han electro-acupuncture apparatus （WQ 1002, No. zun （91）-227270-588, Beijing Anlong Photoelectricity-Technique Company, China）, and T-maze （self-made）. METHODS： A total of 50 mice were randomly divided into 5 groups, with 10 mice in each group： blank control, T-maze, model, model ＋ electro-acupuncture, and electro-acupuncture groups. Establishment of anxiety model after morphine withdrawal： the mouse hot plate assay was used to detect the activity of morphine. The median effective dose of morphine, 2.95 mg/kg, was defined as the base. Mice were subcutaneously administered morphine, 3 times a day, for 4 days successively （initially 2.95 mg/kg, then increased day by day, as described below）. Interventions： In the model ＋ electro-acupuncture group, after model induction, mice were subjected electro-acupuncture at bilateral ＂Sanyinjiao＂ （SP6） points using a Han electro-acupuncture apparatus with sparse-dense waves and frequency of 2-100 Hz, once a day, for 6 days. In the model group, after anxiety-model induction, mice were subjected to fixation as same as model ＋ electro-acupuncture group within 6 days of model induction. In the electro-acupuncture group, the anxiety model was not induced and mice were subjected to fixation, electro-acupuncture and the T-maze test. In the T-maze group, the anxiety model was not induced and mice were subjected to fixation. The T-maze test was performed in the 4 groups after experiment. In the blank control group, the anxiety model was not induced and mice were subjected to fixation only. MAIN OUTCOME MEASURES： Brain tissue norepinephrine content of morphine-withdrawal anxiety mice was detected by fluorospectrophotometry after 6 days of electro-acupuncture. Blood lactic acid content was detected by visible spectrophotometry. RESULTS： A total of 50 mice were included in the final analysis. Brain norepinephrine content was significantly greater in the model group compared to the T-maze, blank control, electro-acupuncture and model ＋ electro-acupuncture groups, （P 〈 0.05-0.01）. Brain norepinephrine content was similar between the model ＋ electro-acupuncture and the blank control groups （P 〉 0.05）. There was no significant difference in blood lactic acid content among the groups （P 〉 0.05）. CONCLUSION： Electro-acupuncture lowers brain norepinephrine content but does not influence peripheral blood lactic acid content in morphine-withdrawn, anxiety-modeled mice. These results demonstrate that anxiety-inhibiting effects of electro-acupuncture, after morphine withdrawal, might be related to regulation of norepinephrine release.
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.
