Our previous studies have shown that analgesia induced by electroacupuncture (EA ) of different frequencies is mediated by different kinds of Opioid peptides. Th us, low frequency (2 Hz) EA increases the release of en...Our previous studies have shown that analgesia induced by electroacupuncture (EA ) of different frequencies is mediated by different kinds of Opioid peptides. Th us, low frequency (2 Hz) EA increases the release of enkepahlins (ENK) and beta endorphin (END) in the central nervous system, whereas high frequency EA (100 Hz) increases the release of dynorphin (DYN) in the spinal cord. In recent years , ne w experiments have yielded new data that further substantiate the hypothesis put forward several years ago. 1. How to accelerate the release of endomorphin (EM) in the central nervous syst em EM is an endogenously produced morphine like peptide composed of 4 amino aci ds, showing a high specificity to mu Opioid receptor. Han et al (1999) have show n that intrathecal injection of anti EM antibody to the rat spinal cord blocked 2 Hz but not 100 Hz EA induced analgesia. Likewise, intracerebroventricular (IC V) injection of anti EM antibody or the mu receptor blocker CTOP attenuated 2 H z but not 100 Hz EA induced analgesia (Huang et al, 2000). The results suggest tha t 2 Hz EA accelerated the release of EM in brain and spinal cord to interact wit h mu Opioid receptor to produce analgesic effect. High frequency EA was not effec tive. 2. How to activate both neural pathways mediating both low and high frequency EA effect Pharmacological studies have shown that intrathecal injection of both enkepah lin and dynorphin produces a synergistic analgesic effect. It would naturally l ead to the supposition that EA analgesia may be potentiated if one could activat e both pathways simultaneously. Two paradigms could be used. Paradigm A is to us e low frequency (LF) and high frequency (HF) alternatively, each lasting for a c ertain period (already optimized to be 3 sec). Paradigm B is to use LF in one li mb and HF in another limb. Pharmacological studies were used to analyze the recept or mechanisms; neurochemical detection and antibody microinjection technique wer e used to identify the neuropeptides responsible for producing the analgesic eff ect. All three lines of evidence pointed to the conclusion that it was the parad igm A which produced the maximal (synergistic) effect, whereas paradigm B produc ed an effect almost identical to that of 100 Hz EA. The results suggested that in the later case, the signal of 2 Hz was immersed into and masked by that of 100 H z, and could not stand out as an independent component of LF EA (to be published ). 3. Effect of EA on neuropathic pain Neuropathic pain model was constructed by L 5/L 6 nerve ligation in the rat . Mecha nical allodynia was shown by the 50% withdrawal threshold, whereas cold induced ongoing pain was detected by the number of paw lifts from the 5 ℃ cold plate i n 5 min. While EA of both frequencies could reduce mechanical allodynia, the effec t of 2 Hz was much stronger, with a shorter latency and longer duration as compa red to that of 100 Hz stimulation. In terms of relieving the cold induced ongoi n g pain (hyperalgesia), the effect of 2 Hz was also significantly stronger and lo nger lasting (up to 48 hr for one treatment) as compared to 2～4 hr in 100 Hz st imulation (Sun et al, to be published). 4. EA treatment for morphine withdrawal syndrome and for craving For the treatment of withdrawal syndrome, including tachycardia, weight loss and wet dog shakes in the rat, 100 Hz EA was better than 2 Hz EA. This was true not only in the rat experiment but also in the humans. High rate of relapse characterized the outcome of drug abusers after the success ful detoxification, and craving may constitute the main cause of relapse. In ord er to study the mechanisms of Opioid craving, an animal model is indispensable. A conditioned place preference (CPP) model was constructed in this laboratory, a nd stress or drug priming was used for the reinstatement of the extinguished CPP . In this model, it was only 2 Hz or 2/100 Hz, but not pure 100 Hz peripheral stimulation, that was effective to suppress the CPP. Thus, a sharp contrast can be made展开更多
Brain functions are regulated by neurotransmitters and/or neuromodulators,including neuropeptides.It has been shown that electrical stimulation of identified frequencies placed on certain sites of the body would induc...Brain functions are regulated by neurotransmitters and/or neuromodulators,including neuropeptides.It has been shown that electrical stimulation of identified frequencies placed on certain sites of the body would induce the release of specific neuropeptides in the central nervous system.This may explain,at least partly,the mechanisms by which acupuncture exerts its therapeutic effects.展开更多
文摘Our previous studies have shown that analgesia induced by electroacupuncture (EA ) of different frequencies is mediated by different kinds of Opioid peptides. Th us, low frequency (2 Hz) EA increases the release of enkepahlins (ENK) and beta endorphin (END) in the central nervous system, whereas high frequency EA (100 Hz) increases the release of dynorphin (DYN) in the spinal cord. In recent years , ne w experiments have yielded new data that further substantiate the hypothesis put forward several years ago. 1. How to accelerate the release of endomorphin (EM) in the central nervous syst em EM is an endogenously produced morphine like peptide composed of 4 amino aci ds, showing a high specificity to mu Opioid receptor. Han et al (1999) have show n that intrathecal injection of anti EM antibody to the rat spinal cord blocked 2 Hz but not 100 Hz EA induced analgesia. Likewise, intracerebroventricular (IC V) injection of anti EM antibody or the mu receptor blocker CTOP attenuated 2 H z but not 100 Hz EA induced analgesia (Huang et al, 2000). The results suggest tha t 2 Hz EA accelerated the release of EM in brain and spinal cord to interact wit h mu Opioid receptor to produce analgesic effect. High frequency EA was not effec tive. 2. How to activate both neural pathways mediating both low and high frequency EA effect Pharmacological studies have shown that intrathecal injection of both enkepah lin and dynorphin produces a synergistic analgesic effect. It would naturally l ead to the supposition that EA analgesia may be potentiated if one could activat e both pathways simultaneously. Two paradigms could be used. Paradigm A is to us e low frequency (LF) and high frequency (HF) alternatively, each lasting for a c ertain period (already optimized to be 3 sec). Paradigm B is to use LF in one li mb and HF in another limb. Pharmacological studies were used to analyze the recept or mechanisms; neurochemical detection and antibody microinjection technique wer e used to identify the neuropeptides responsible for producing the analgesic eff ect. All three lines of evidence pointed to the conclusion that it was the parad igm A which produced the maximal (synergistic) effect, whereas paradigm B produc ed an effect almost identical to that of 100 Hz EA. The results suggested that in the later case, the signal of 2 Hz was immersed into and masked by that of 100 H z, and could not stand out as an independent component of LF EA (to be published ). 3. Effect of EA on neuropathic pain Neuropathic pain model was constructed by L 5/L 6 nerve ligation in the rat . Mecha nical allodynia was shown by the 50% withdrawal threshold, whereas cold induced ongoing pain was detected by the number of paw lifts from the 5 ℃ cold plate i n 5 min. While EA of both frequencies could reduce mechanical allodynia, the effec t of 2 Hz was much stronger, with a shorter latency and longer duration as compa red to that of 100 Hz stimulation. In terms of relieving the cold induced ongoi n g pain (hyperalgesia), the effect of 2 Hz was also significantly stronger and lo nger lasting (up to 48 hr for one treatment) as compared to 2～4 hr in 100 Hz st imulation (Sun et al, to be published). 4. EA treatment for morphine withdrawal syndrome and for craving For the treatment of withdrawal syndrome, including tachycardia, weight loss and wet dog shakes in the rat, 100 Hz EA was better than 2 Hz EA. This was true not only in the rat experiment but also in the humans. High rate of relapse characterized the outcome of drug abusers after the success ful detoxification, and craving may constitute the main cause of relapse. In ord er to study the mechanisms of Opioid craving, an animal model is indispensable. A conditioned place preference (CPP) model was constructed in this laboratory, a nd stress or drug priming was used for the reinstatement of the extinguished CPP . In this model, it was only 2 Hz or 2/100 Hz, but not pure 100 Hz peripheral stimulation, that was effective to suppress the CPP. Thus, a sharp contrast can be made
文摘Brain functions are regulated by neurotransmitters and/or neuromodulators,including neuropeptides.It has been shown that electrical stimulation of identified frequencies placed on certain sites of the body would induce the release of specific neuropeptides in the central nervous system.This may explain,at least partly,the mechanisms by which acupuncture exerts its therapeutic effects.
