Electroacupuncture Ameliorates Propofol-Induced Cognitive Impairment via an Opioid Receptor-Independent Mechanism.

While general anesthesia is known to induce cognitive deficits in elderly and pediatric patients, its influence on adults is less well-characterized. The present study was designed to evaluate the influence of propofol on the learning and memory of young adult rats, as well as the potential neuroprotective role of electroacupuncture (EA) in propofol-induced cognitive impairment. Intravenous anesthesia with propofol was administered to young adult male Sprague-Dawley (SD) rats for 6 h, and EA was administered three times before and after anesthesia. The Morris Water Maze (MWM) test was conducted to determine the rat's cognitive performance following the anesthesia treatment. Our results showed that propofol induced obvious cognitive impairment in young adult rats, which could be ameliorated by multiple EA treatments. Moreover, the decreased level of phosphorylated glycogen synthase kinase 3 ß (pGSK-3ß) in the CA1 region of the hippocampus accompanying the cognitive impairment was also reversed by EA treatment. Further experiments demonstrated that neither 2 nor 10 mg/kg (I.P.) naloxone blocked the effect of EA, indicating that the neuroprotective effect of EA on propofol-induced cognitive impairment was not mediated via the opioid receptors. The present study suggests that EA could ameliorate the cognitive impairment induced by prolonged anesthesia with propofol in young adult rats, which is likely associated with pGSK-3ß levels in the CA1 independently of opioid receptors. These findings imply that EA may be used as a potential neuroprotective therapy for post-operative cognitive dysfunction (POCD).

Transcutaneous electrical acupoint stimulation for the treatment of withdrawal syndrome in heroin addicts.

OBJECTIVE: To assess the therapeutic effect of transcutaneous electric acupoint stimulation (TEAS) for the treatment of withdrawal syndrome in heroin addicts. METHODS: A total of 63 male heroin addicts with withdrawal score higher than 20 were recruited in the Detoxification Center of Zhongshan city, Guangdong province, China. They were randomly distributed into two groups: TEAS group (n = 31) received TEAS by using a Han's acupoint nerve stimulator (HANS) model 200A with two output channels, 2-3 sessions per day, 30 minutes per session for 10 consecutive days. Electrical stimulation of alternating frequencies of 2- and 100-Hz with 3 second each, and with intensity of 10-15 mA was applied on Hegu (LI-4) and Laogong (PC-8) points on one hand, and Neiguan (PC-6) and Waiguan (SJ-5) points on the other forearm via electroconductive skin pads of 4 cm × 4 cm in size. The control group (n = 32) was treated with similar procedure except that the leads of the output of the stimulator was disconnected. Assessments of the severity of the withdrawal syndrome were conducted one day before and on each day during the whole treatment period of 10 days. Buprenorphin of 1 mg per day sublingually was provided to all subjects in the first two days, and then to those with withdrawal score over 20 in the following days. RESULTS: The TEAS treatment dramatically alleviated the withdrawal syndrome during heroin detoxification. No significant difference was found in withdrawal scores between the two groups at the beginning of the observation. Withdrawal scores showed a more marked drop in TEAS group than the control starting from the second day, and maintained at a lower level for the whole course of treatment. The area under the curve of withdrawal score in TEAS group was only 40% of that in the control (P < 0.001, two way repeated measures analysis of variance), and the requirement of buprenorphine was only 10% of that in the control. No adverse effects were observed in either group. CONCLUSION: TEAS of 2/100 Hz for 10 days in abrupt abstinence of the heroin addicts resulted in a marked reduction of the withdrawal syndrome as well as a reduced requirement for rescue opioids.

Acupuncture for the treatment of drug addiction.

Over the last four decades, there has been an increasing interest in acupuncture treatment of substance abuse around the world. Three important steps can be identified in this field. Dr. Wen of Hong Kong was the first (1972) to report that acupuncture at four body points and two ear points combined with electric stimulation can relieve opioid withdrawal signs in the addicts. The second major step was made by Dr. M. Smith in New York, the head of the National Acupuncture Detoxification Association (NADA) of the United States, who finalized a protocol (1985), using only ear points without electric stimulation for the treatment of cocaine dependence. The recent advance in this field was made by Dr. Han of the Peking University, Beijing, who characterized a protocol (2005), using electric stimulation of identified frequencies on body points to ameliorate heroin withdrawal signs and reduce relapse of heroin use. In this chapter, the efficacy of acupuncture and related techniques for the treatment of drug dependence in experimental settings and clinical practice will be reviewed, and the possible mechanisms underlying this effect be discussed.

Damage of splenic T lymphocyte proliferation and differentiation and its normalization by electroacupuncture in morphine-dependent mice mode.

In a previous paper we reported that electroacupuncture (EA) could suppress opioid withdrawal syndrome and increase the appetite, sleep, and body weight in heroin addicts or morphine dependent animals. Considering that opioids were known to inhibit immune function, the present study was designed to observe whether EA could modulate the immune status of morphine dependent and withdrawal mice. We found that chronic morphine-induced decrease of splenic T lymphocyte proliferation and IL-2 production can be significantly raised by 2 Hz EA, and the fluctuation of CD4(+)/CD8(+) ratio was also run to the baseline level by the EA. These findings indicated that chronic morphine exposure-induced immune dysfunction in mice could be normalized by 2 Hz EA.

Multiple 100 Hz electroacupuncture treatments produced cumulative effect on the suppression of morphine withdrawal syndrome: Central preprodynorphin mRNA and p-CREB implicated.

Alleviating opiate withdrawal syndrome in addicts is a critical precondition to break away from drug and further to prevent reuse. Electroacupuncture (EA) was claimed to be effective for alleviating withdrawal syndrome, but the optimal protocol remained unclear. In the present study we found that (1) 100 Hz EA administered 12-24h after the last morphine injection suppressed the withdrawal syndrome in rats, multiple sessions of EA were more effective than single session, with the after-effect lasting for at least 7 days. (2) A down-regulation of preprodynorphin (PPD) mRNA level was observed in spinal cord, PAG and hypothalamus 60 h after the last morphine injection, which could be reversed by multiple sessions, but not a single session of EA. (3) Accompanied with the decrease of PPD mRNA level, there was an up-regulation of p-CREB in the three CNS regions, which was abolished by 100 Hz EA treatment. The findings suggest that down-regulation of p-CREB and acceleration of dynorphin synthesis in spinal cord, PAG and hypothalamus may be implicated in the cumulative effect of multiple 100Hz EA treatment for opioid detoxification.

Electroacupuncture treatment normalized sleep disturbance in morphine withdrawal rats.

Sleep disturbance is considered as an important symptom of acute and protracted opiate withdrawal. Current results suggest that sleep disturbance may be taken as a predictor of relapse. Appropriate sleep enhancement therapy will be in favor of the retention in treatment for opiate addicts. Our previous studies have shown that electroacupuncture (EA) is effective in suppressing morphine withdrawal syndrome. The aim of the present study is to investigate the effect of 2 and 100 Hz EA on the sleep disturbance during morphine withdrawal. Rats were made dependent on morphine by repeated morphine injections (escalating doses of 5-80 mg kg(-1), subcutaneously, twice a day) for 5 days. EA of 2 or 100 Hz was given twice a day for 3 days, starting at 48 h after the last morphine injection. Electroencephalogram and electromyogram were monitored at the end of the first and the last EA treatments, respectively. Results showed that non-rapid eye movement (NREM) sleep, REM sleep and total sleep time decreased dramatically, while the sleep latency prolonged significantly during acute morphine withdrawal. Both 2 and 100 Hz EA produced a significant increase in NREM sleep, REM sleep and total sleep time. It was suggested that EA could be a potential treatment for sleep disturbance during morphine withdrawal.

Morphine-induced conditioned place preference in rats is inhibited by electroacupuncture at 2 Hz: role of enkephalin in the nucleus accumbens.

Our previous studies have demonstrated that morphine-induced conditioned place preference (CPP) can be inhibited by 2 Hz electroacupuncture (EA). This inhibition can be blocked by either the opioid receptor antagonist naloxone (i.p.) or lesion in the nucleus accumbens (NAc), providing evidence that endogenous opioid system in the NAc mediates the effects of EA. Here we report that 1) A single session of 2 Hz EA produced a significant increase of the content of enkephalin in the NAc of morphine-induced CPP rats, and this effect was stronger in three consecutive sessions of EA; 2) Intracerebroventricular injection of the mu-opioid receptor antagonist CTAP or delta-opioid receptor antagonist NTI, but not kappa-opioid receptor antagonist nor-BNI, dose-dependently reversed the inhibitory effects of 2 Hz EA on the expression of morphine-induced CPP; 3) Three consecutive sessions of 2 Hz EA up-regulated the mRNA level of preproenkephalin in the NAc of morphine-induced CPP rats. The results suggest that the inhibitory effects of 2 Hz EA on the expression of the morphine CPP is mediated by mu- and delta-, but not kappa-opioid receptor, possibly via accelerating both the release and synthesis of enkephalin in the NAc. These findings support the possibility of using 2 Hz EA for the treatment of opiate addiction.

Acupuncture for the treatment of drug addiction.

Over the last three decades there has been an increasing interest in acupuncture treatment of substance abuse around the world. Three important steps can be identified in this field. Dr. Wen of Hong Kong was the first (1972) to report that acupuncture at 4 body points and 2 ear points combined with electrical stimulation can relieve opioid withdrawal signs in the addicts. The second major step was made by Dr. M. Smith in New York, the head of the National Acupuncture Detoxification Association (NADA) of the USA, who finalized a protocol (1985), using only ear points without electrical stimulation for the treatment of drug abuse. The recent advance in this field was made by Dr. Han of the Peking University, Beijing, who characterized a protocol (2005), using electrical stimulation of identified frequencies on body points to ameliorate heroin withdrawal signs and prevent relapse of heroin use. In this review, the efficacy of acupuncture and related techniques for the treatment of drug dependence in experimental settings and clinical practice will be reviewed, and the possible mechanisms underlying this effect be discussed.

The Neuroscience Research Institute at Peking University: a place for the solution of pain and drug abuse.

Neuroscience research in China has undergone rapid expansion since 1980. The Neuroscience Research Institute of Peking University, one of the most active neuroscience research groups in China, was founded in 1987. Currently, the institute is overseeing four research areas, i.e., (1) pain and analgesia, (2) drug abuse and acupuncture treatment for drug addiction, (3) the mechanism of neurological degenerative disorders, and (4) the role of neuroglia in central nervous system injury. The institute is simultaneously investigating both theoretical and clinical studies. Acupuncture remains the core of research, while pain and drug abuse form the two disciplines.

[Acupuncture for the treatment of drug addiction].

Over the last three decades there has been an increasing interest in acupuncture treatment of substance abuse around the world. Three important steps can be identified in this field. Dr. H. L. Wen of Hong Kong was the first (1973) to report that acupuncture at 4 body points and 2 ear points combined with electrical stimulation can relieve opiate withdrawal signs in the addicts. The second major step was made by Dr. M. Smith in New York, the head of the National Acupuncture Detoxification Association (NADA) of the U.S.A., who finalized a protocol (1985), using only ear points without electrical stimulation for the treatment of drug abuse. The recent advance in this field was made by Prof. J. S. Han and his colleagues in Neuroscience Research Institute of the Peking University, Beijing, who characterized a protocol (1992- ), using electrical stimulation of identified frequencies on body points to ameliorate heroin withdrawal signs and prevent relapse to heroin use. In this review, the efficacy of acupuncture and related techniques for the treatment of drug dependence in experimental settings and clinical practice will be reviewed, and the possible mechanisms underlying this effect be discussed.

Suppression of cue-induced heroin craving and cue-reactivity by single-trial transcutaneous electrical nerve stimulation at 2 Hz.

The purpose of the present study was to investigate the efficacy of 2 Hz transcutaneous electrical nerve stimulation (TENS) to reduce cue-induced heroin craving and the corresponding cardiovascular responses. Seventy heroin addicts with at least 1 month of abstinence were enrolled and randomly divided into two groups of 35, to receive single-trial 2 Hz TENS (TENS group) or mock TENS (mock group) during experimental procedure, respectively. They were required to express their degree of craving by visual analog scale before and after the presentation of a video-cue, and after TENS treatment, which lasted for 30 minutes. Heart rate and arterial blood pressure were simultaneously monitored in 56 cases, with 28 in each group. Results show that in mock group, video-cue induced a dramatic increase of craving score, which did not return to baseline in 150 minutes, whereas in the TENS group, 2 Hz TENS treatment produced a significant decrease of craving, reaching baseline in 90 minutes. Video-cue induced a significant increase of heart rate and systolic and diastolic blood pressure, which remained elevated for at least 60 minutes in the mock group; whereas in the TENS group, they returned to baseline immediately after the termination of TENS. These results indicate that the craving induced by a heroin-related cue can be immediately and significantly suppressed, and the cardiovascular activation totally abolished by a single-trial 2 Hz TENS for 30 minutes.

Electroacupuncture facilitates recovery of male sexual behavior in morphine withdrawal rats.

The effect of electroacupuncture (EA) on the sexual behavior of male rats undergoing morphine withdrawal was studied by measuring various parameters of sexual behavior. In addition, the total serum testosterone (TST) concentrations in male rats at different times of morphine administration and abstinence were measured. Acute and chronic administration of morphine severely inhibited the sexual behavior of the rats and lowered their TST concentrations. TST concentrations recovered to normal within 24 h after the last morphine injection, while sexual behavior remained suppressed for at least 7 days. Electroacupuncture (2/100 Hz alternately) administered once daily for 7 days during morphine withdrawal facilitated the recovery of male sexual behavior and increased TST concentrations to above normal. The effect of EA on sexual behavior may involve both neuronal and hormonal pathways.