Effects of acupuncture on stress-induced relapse to cocaine-seeking in rats

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I can't evaluate the validity of this study, but wanted to cite it because they use the same point, Heart 7, as in this study, that looked at alcoholism in rats.  In the clinic there is a decline in alcohol consumption in patients that is quite pronounced.  The two studies look at different mechanisms for the craving and effect of acupuncture, but I wanted to draw attention to the similarity.

Effects of acupuncture on stress-induced relapse to cocaine-seeking in rats.
Yoon SS, Yang EJ, Lee BH, Jang EY, Kim HY, Choi SM, Steffensen SC, Yang CH.Psychopharmacology (Berl). 2012 Mar 29.
College of Oriental Medicine, Daegu Haany University, 165 Sang-Dong, Suseong-Gu, Daegu, 706-828, South Korea.
Abstract
RATIONALE:
Cocaine addiction is associated with high rates of relapse, and stress has been identified as a major risk factor. We have previously demonstrated that acupuncture reduces drug self-administration and dopamine release in the nucleus accumbens (NAc), a brain structure implicated in stress-induced reinstatement of drug-seeking behavior.
OBJECTIVE:
This study was conducted to investigate the effects of acupuncture on footshock-induced reinstatement of cocaine-seeking and the expression of c-Fos and the transcription factor cAMP response element-binding protein (CREB) in the NAc, used as markers of neuronal activation in conditions of stress-induced reinstatement to cocaine.
METHODS:
Male Sprague-Dawley rats were trained to self-administer cocaine (1.0 mg/kg) for 14 days, followed by extinction and then footshock stress. Acupuncture was applied at bilateral Shenmen (HT7) points for 1 min after footshock stress.
RESULTS AND CONCLUSIONS:
Acute footshock stress reinstated cocaine-seeking behavior and enhanced c-Fos expression and phosphorylated CREB (pCREB) activation in the NAc shell in cocaine pre-exposed rats. On the other hand, acupuncture at HT7, but not at control point (LI5), markedly reduced reinstatement of cocaine-seeking (86.5 % inhibition vs. control value), c-Fos expression (81.7% inhibition), and pCREB activation (79.3% inhibition) in the NAc shell. These results suggest that acupuncture attenuates stress-induced relapse by regulating neuronal activation in the NAc shell.
http://www.ncbi.nlm.nih.gov/pubmed/22453546

Brain Chemistry Involved in Electroacupuncture Analgesia

A nice study from University of Maryland from Lixing Lao who does excellent all around work, but is particularly interested in using rat arthritis models to explore the mechanisms of acupuncture. I've discussed his work here and here among other citations.  The abstract is copied in its entirety here.

http://www.ncbi.nlm.nih.gov/pubmed/21565329
Brain Res. 2011 Jun 13;1395:38-45. Epub 2011 Apr 28.
Rostral ventromedial medulla μ, but not κ, opioid receptors are involved in electroacupuncture anti-hyperalgesia in an inflammatory pain rat model.
Zhang Y, Li A, Lao L, Xin J, Ren K, Berman BM, Zhang RX.

Source
Center for Integrative Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.

Abstract
It has been reported that intracerebroventricular injection of a μ receptor antagonist blocked 2 but not 100Hz electroacupuncture (EA)-produced analgesia in an uninjured animal model. Because persistent pain changes neural response to external stimulation, we hypothesized that the mechanisms of EA anti-hyperalgesia may be different in persistent pain than in health. Hyperalgesia, decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, was induced by subcutaneously injecting complete Freund's adjuvant (CFA) into the hind paws of rats. Selective antagonists against μ (CTOP: D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2, 6.25 nmol) and κ (Nor-BIN: nor-binaltorphimine, 10 nmol) opioid receptors were infused into the rostral ventromedial medulla (RVM) 10 min before a 30-min EA treatment at acupoint Huantiao (GB30) 1h 30 min post-CFA. PWL was measured before and 2.5 post-CFA. Both 10 Hz and 100 Hz EA-produced anti-hyperalgesia were blocked by intra-RVM μ, but not κ, receptor antagonists. Double immunofluorescence staining demonstrated that μ receptor-containing neurons were GABAnergic and that GABAa receptor-containing neurons were serotonergic in the RVM. The results demonstrated an involvement of RVM μ, but not κ, receptors in EA-produced anti-hyperalgesia. In summary, EA may induce release of endogenous endomorphins that activate μ opioid receptors in GABAnergic neurons to suppress the release of GABA. This removes the tonic inhibition of GABA on serotonergic neurons in the RVM, and activation of these serotonergic neurons inhibits pain. EA may be used as complementary treatment for inflammatory pain.

Acupuncture suppresses bladder activity: Animal Study

This is an interesting study performed in rats showing that the inhibitory effect on micturition (urination) by acupuncture takes place in the brainstem. This is surprising to me, since I would have thought it was more of a spinal reflex/gating mechanism. (info on my practice here)

Acupuncture of the sacral vertebrae suppresses bladder activity and bladder activity-related neurons in the brainstem micturition center.
Wang H, Tanaka Y, Kawauchi A, Miki T, Kayama Y, Koyama Y.
Department of Physiology, Guiyang College of Traditional Chinese Medicine, Guiyang 550001, China
Acupuncture of the sacral vertebrae has therapeutic effects in patients with overactive bladders. The mechanism of these effects, however, remains unclear. The present study, using urethane-anesthetized rats, investigated the effects of acupuncture stimulation of the sacral vertebrae on bladder activity and bladder activity-related neurons in and around Barrington's nucleus. In 95 of 147 trials (64.6%), acupuncture stimulation of the sacral vertebrae for 1 min suppressed bladder contraction for 27-2347s...These findings suggest that acupuncture stimulation of the sacral vertebrae suppresses bladder contraction and changes the firing properties of bladder activity-related neurons in and around Barrington's nucleus, and that these changes are mediated by GABAergic systems.

HRV and Auricular Acupuncture in Rats

(info on my practice here.)

This is another Litscher study, full text article for free here. He has done a series of articles on HRV and acupuncture which we have discussed here, here, here, and here. This one is the first to use animal data. It’s a combined Chinese/Austrian study in that the studies are done in China and then the data transmitted to Austria and analysed. At least that is my understanding of his work. In this study, the decrease in LFR/HFR with stimulation at St36 was corroborated, albeit in rats. An overall increase in HRV was found only in ear acupuncture. ( It is amazing to me that they could even distinguish various acupunpoints on a tiny rat ear, but that was the protocol. They used the heart point, in case you’re interested.) We discussed stimulation of Stomach 36 and its effect on autonomic balance here, and here

Evid Based Complement Alternat Med. 2012;2012:817378. Epub 2012 Feb 21.
Sino-European transcontinental basic and clinical high-tech acupuncture studies-part 1: auricular acupuncture increases heart rate variability in anesthetized rats.
Gao XY, Liu K, Zhu B, Litscher G.
Source

Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Dongzhimen Nanxiaojie Street, Beijing 100700, China.
Abstract

Evidence-based research concerning the effects of high-tech acupuncture on autonomic function was performed by two research teams from China and Austria. This study describes the first transcontinental teleacupuncture measurements in animals. Heart rate (HR) and heart rate variability (HRV) recordings in 10 male Sprague-Dawley anesthetized rats were performed under stable conditions in Beijing, China, and the data analysis was completed in Graz, Austria. The electrocardiograms (ECGs) were recorded by an HRV Medilog AR12 system during acupuncture of the ear and body (PC6 Neiguan, CV12 Zhongwan, ST36 Zusanli). The data were analyzed using specially adapted novel Austrian software. HR did not change significantly during any acupuncture stimulation in anesthetized rats (ear acupuncture, PC6, CV12, or ST36). Total HRV only changed significantly (P = 0.025) during auricular acupuncture (acupoint heart). The low-frequency/high-frequency ratio parameter decreased significantly (P = 0.03) during stimulation of ST36. This change was based on intensification of the related mechanism of blood pressure regulation that has been demonstrated in previous studies in humans. Modernization of acupuncture research

Electroacupuncture at St36 prevents stress induced increases in neuropeptide Y in rats

This study confirms the value of electroacupuncture at St36 in reducing one of the sympathetic pathways involved in the stress response and adds some additional evidence. This effect was discussed in different contexts here and here. In the first post electroacupuncture at St36 was used for migraine prophylaxis and was found to decrease the stress response (decrease LFR/HFR.) In the second post, electroacupuncture was used to decrease blood pressure.
Exp Biol Med (Maywood). 2012 Jan 1;237(1):18-23. Epub 2011 Dec 7.

Acupuncture at ST36 prevents chronic stress-induced increases in neuropeptide Y in rat.
Eshkevari L, Egan R, Phillips D, Tilan J, Carney E, Azzam N, Amri H, Mulroney SE.
Department of Nursing, School of Nursing and Health Studies, Georgetown University Medical Center, Washington, DC 20007, USA. eshkevl@georgetown.edu

Chronic stress, as seen in post-traumatic stress disorder, can exacerbate existing diseases. Electroacupuncture (EA) has been proposed to treat chronic stress, although information on its efficacy or mechanism(s) of action is limited. While many factors contribute to the chronic stress response, the sympathetic peptide, neuropeptide Y (NPY), has been shown to be elevated in chronic stress and is hypothesized to contribute to the physiological stress response. Our objective was to determine if EA at acupuncture point stomach 36 (ST(36)) is effective in mitigating cold stress-induced increase in NPY in rats. Both pretreatment and concomitant treatment with EA ST(36) effectively suppressed peripheral and central NPY after 14 d of cold stress (P < 0.05). The effect was specific, as NPY in Sham-EA rats was not different than observed in stress-only rats. Additionally, the effect of EA ST(36) was long-lasting, as NPY levels remained suppressed despite early cessation of EA ST(36), while exposure to cold stress was continued. In the paraventricular nucleus (PVN), it was notable that changes in NPY mirrored plasma NPY levels, and that the significant elevation in PVN Y1 receptor observed with stress was also prevented with EA ST(36). The findings indicate that EA ST(36) is effective in preventing one of the sympathetic pathways stimulated during chronic stress, and thus may be a useful adjunct therapy in stress-related disorders.

Post Spinal Nerve Ligation Hypersensitivity Relieved by Manual Acupuncture (in rats)

This study is looking at acupuncture effectiveness for neuropathic pain. They simulate neuropathic pain by ligating a spinal nerve in the rat and then using traditional acupuncture point stimulation compared with gabapentin.

Manual acupuncture inhibits mechanical hypersensitivity induced by spinal nerve ligation in rats.
Cidral-Filho FJ, da Silva MD, Moré AO, Córdova MM, Werner MF, Santos AR.
Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brasil.
Abstract

Manual acupuncture (MA) has presented analgesic activity against neuropathic pain in patients and animal models, yet a series of questions remain: Is MA effectiveness dependent of acupoint selection or combination? Is it equally efficient when treatment starts on the initial (acute) or sub-chronic phase of spinal nerve ligation (SNL)-induced neuropathy? Is MA effect related to the release of endogenous opioids? Does MA produce similar effects to gabapentin? To answer these questions rats submitted to the L5/L6 SNL injury were treated with unilateral MA (ST36 (Zusanli), SP6 (Sanyingjiao) or ST36+SP6 acupoint stimulation); or with gabapentin (30 mg/kg i.p., used as positive control). Both acupoints have been demonstrated to present analgesic activity and are used in clinical practice and basic science research. In addition, we investigated the influence of naloxone (1 mg/kg i.p., a nonselective opioid receptor antagonist) on MA treatment and also the effect of unilateral ST36+SP6 MA treatment beginning acutely (5 days) or sub-chronically (14 days) after SNL. Our results demonstrate that single or combined unilateral stimulation was able to reduce mechanical hypersensitivity with treatment beginning in both acute and sub-chronic phases of SNL-induced neuropathy; MA effect was blocked by naloxone, and finally; SP6+ST36 MA presented similar effect to gabapentin (30 mg/kg). In conclusion, our results demonstrate, for the first time, that unilateral MA (ST36, SP6 or ST36+SP6) reduces hypersensitivity induced by the SNL with effect dependent of the opioid system and comparable with the one obtained with gabapentin (used as positive control).

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