Objective: To investigate the possible mechanisms in acupuncture analgesia by interaction of δ-opioid receptor with neurotransmitter transport proteins or the Na^+-K^+ pump. Methods: Microinjection of respective ...Objective: To investigate the possible mechanisms in acupuncture analgesia by interaction of δ-opioid receptor with neurotransmitter transport proteins or the Na^+-K^+ pump. Methods: Microinjection of respective heterologous cRNA into the Xenopus oocytes as a model system, and measurement of steady-state currents under two-electrode voltage clamp. Results: The co-expression of the 8-opioid receptor with GAT1, EAAC 1 or the sodium pump resulted in reducing activity of the respective transporter. Opioid receptor activation affected transporter activity in different ways: 1) GAT1 was further inhibited; 2) EAAC1 was stimulated; 3) Na^+-K^+ pump activity interfered with agonist sensitivity of DOR. Pump inhibition led to higher sensitivity for DPDPE. Conclusion: GABA transporter inhibition and glutamate transporter stimulation may counteract pain sensation by affecting the neurotransmitter concentration in the synaptic cleft and, therefore, may contribute synergistically to pain suppression by acupuncture. Sodium pump inhibition by endogenous ouabain may amplify these effects. These synergistic effects may be the molecular mechanism of inhibiting pain sense and/or acupuncture analgesia.展开更多
Objective:To explore the central neurobiological mechanisms of pleasure effect on rats with neuralgia treated by tuina manipulations of An-pressing and Rou-kneading Huantiao (GB 30).Methods:A total of 64 male Sprague-...Objective:To explore the central neurobiological mechanisms of pleasure effect on rats with neuralgia treated by tuina manipulations of An-pressing and Rou-kneading Huantiao (GB 30).Methods:A total of 64 male Sprague-Dawley (SD) rats were used in this study.Eighteen rats were randomly selected as a normal group,and the other 46 rats were used to duplicate the chronic constriction injury (CCI) model.Ten rats failed in modeling and 36 rats succeeded.These 36 rats were then randomly divided into a model group and a tuina group,with 18 rats in each group.The rats in the normal group and the model group did not receive any interventions,while those in the tuina group received An-pressing and Rou-kneading Huantiao (GB 30),1 min for each time,once a day,3 weeks in total.Heating tests were evaluated to observe the change of pain-sensitivity score before intervention,1 week after intervention,2 weeks after intervention,and 3 weeks after intervention.After 1 week of intervention,2 weeks of intervention,and 3 weeks of intervention,6 rats were randomly selected from each group respectively for brain extraction.The change of Nissl's body and β-endorphin in the accumbens nucleus as well as amygdaloid nucleus of pleasure circuits,and pro-opiomelanocortin (POMC) in the arcuate nucleus were analyzed by methods of histochemistry and molecular biology.Results:After modeling,the pain-sensitivity scores of the tuina group and the model group were statistically different from the score of the normal group (both P<0.05).After An-pressing and Rou-kneading Huantiao (GB 30) for one week,the pain-sensitivity score of the tuina group had statistical difference compared with that of the model group (P<0.05).At each different time point:the amounts of Nissl's body in accumbens nucleus and amygdaloid nucleus of the tuina group were significantly more than those of the model group (all P<0.01).Besides,the numbers of β-endorphin immunoreactive cells in the accumbens nucleus and amygdaloid nucleus of the rats in the tuina group were significantly higher than those in the model group (all P<0.01),and so was the expression of POMC in arcuate nucleus (all P<0.01).Conclusion:An-pressing and Rou-kneading Huantiao (GB 30),where the sciatic nerve is ligated,can reduce pain-sensitivity score and increase pain tolerance value of rats with chronic neuralgia.It can increase the activity of neurons in accumbens nucleus and amygdaloid nucleus of pleasure circuits,which indicates that the analgesia effect of tuina therapy may correlate with pleasure effect,and also reveals a part of neurobiological mechanisms of neuralgia.展开更多
基金the Science Foundation of Shanghai Municipal Commission of Science and Technology(05DZ19745,06DZ19732,064319053,07DZ19722,07DZ19733)the National Basic Research Program of China(973 Program,2005CB523306)Shanghai Leading Academic Discipline Project(B112 and T0302)
文摘Objective: To investigate the possible mechanisms in acupuncture analgesia by interaction of δ-opioid receptor with neurotransmitter transport proteins or the Na^+-K^+ pump. Methods: Microinjection of respective heterologous cRNA into the Xenopus oocytes as a model system, and measurement of steady-state currents under two-electrode voltage clamp. Results: The co-expression of the 8-opioid receptor with GAT1, EAAC 1 or the sodium pump resulted in reducing activity of the respective transporter. Opioid receptor activation affected transporter activity in different ways: 1) GAT1 was further inhibited; 2) EAAC1 was stimulated; 3) Na^+-K^+ pump activity interfered with agonist sensitivity of DOR. Pump inhibition led to higher sensitivity for DPDPE. Conclusion: GABA transporter inhibition and glutamate transporter stimulation may counteract pain sensation by affecting the neurotransmitter concentration in the synaptic cleft and, therefore, may contribute synergistically to pain suppression by acupuncture. Sodium pump inhibition by endogenous ouabain may amplify these effects. These synergistic effects may be the molecular mechanism of inhibiting pain sense and/or acupuncture analgesia.
基金Shanghai University of Traditional Chinese Medicine(上海中医药大学预算内课题,2015YSN13)The Three-year Development Project for Traditional Chinese Medicine of Shanghai(上海市进一步加快中医药事业发展三年行动计划项目,ZY(2018-2020)-CCCX-2001-05).
文摘Objective:To explore the central neurobiological mechanisms of pleasure effect on rats with neuralgia treated by tuina manipulations of An-pressing and Rou-kneading Huantiao (GB 30).Methods:A total of 64 male Sprague-Dawley (SD) rats were used in this study.Eighteen rats were randomly selected as a normal group,and the other 46 rats were used to duplicate the chronic constriction injury (CCI) model.Ten rats failed in modeling and 36 rats succeeded.These 36 rats were then randomly divided into a model group and a tuina group,with 18 rats in each group.The rats in the normal group and the model group did not receive any interventions,while those in the tuina group received An-pressing and Rou-kneading Huantiao (GB 30),1 min for each time,once a day,3 weeks in total.Heating tests were evaluated to observe the change of pain-sensitivity score before intervention,1 week after intervention,2 weeks after intervention,and 3 weeks after intervention.After 1 week of intervention,2 weeks of intervention,and 3 weeks of intervention,6 rats were randomly selected from each group respectively for brain extraction.The change of Nissl's body and β-endorphin in the accumbens nucleus as well as amygdaloid nucleus of pleasure circuits,and pro-opiomelanocortin (POMC) in the arcuate nucleus were analyzed by methods of histochemistry and molecular biology.Results:After modeling,the pain-sensitivity scores of the tuina group and the model group were statistically different from the score of the normal group (both P<0.05).After An-pressing and Rou-kneading Huantiao (GB 30) for one week,the pain-sensitivity score of the tuina group had statistical difference compared with that of the model group (P<0.05).At each different time point:the amounts of Nissl's body in accumbens nucleus and amygdaloid nucleus of the tuina group were significantly more than those of the model group (all P<0.01).Besides,the numbers of β-endorphin immunoreactive cells in the accumbens nucleus and amygdaloid nucleus of the rats in the tuina group were significantly higher than those in the model group (all P<0.01),and so was the expression of POMC in arcuate nucleus (all P<0.01).Conclusion:An-pressing and Rou-kneading Huantiao (GB 30),where the sciatic nerve is ligated,can reduce pain-sensitivity score and increase pain tolerance value of rats with chronic neuralgia.It can increase the activity of neurons in accumbens nucleus and amygdaloid nucleus of pleasure circuits,which indicates that the analgesia effect of tuina therapy may correlate with pleasure effect,and also reveals a part of neurobiological mechanisms of neuralgia.