Mechanisms of action – Acupuncture and neurotransmitters in the body

We know from research that acupuncture affects many bodily systems, so here we shall take a look at the nervous system and its chemical messengers: neurotransmitters.

In simple terms, a neurotransmitter is a chemical substance released at the end of a nerve fibre, which diffuses across a synapse (junction between nerves), and transmits the signal along to a nerve fibre or muscle fibre, for example.

This process is involved in the transmission of pain signals in the body, and is also one of the well-understood mechanisms of acupuncture pain relief. The role of acupuncture in modulating neurotransmitters involved in pain has been well discussed, as well as researched in great detail.

Specific neurotransmitters, and acupuncture’s effect on them:

Model of a brain and nerve cell

Zhang et al (2022) give the research on those in turn; opioid peptides; γ-Aminobutyric acid (GABA); Norepinephrine; 5-Hydroxytryptamine (5-HT) aka serotonin; and glutamate.  

The researchers look in detail about what acupuncture research has shown in terms of mechanisms of action for each neurotransmitter, and to summarise:

  • Endogenous opioid peptides (a type of neurotransmitter) are produced in the body as a direct result of acupuncture treatment. These have been shown in numerous studies to have a positive effect on analgesia (pain relief).  By name, these are enkephalins, endomorphins, dynorphins, and nociceptin, and they are the body’s own natural painkilling substances
  • γ-Aminobutyric acid (GABA); this is an inhibitory neurotransmitter in the central nervous system.  It has a painkilling effect. It has been demonstrated through research studies that acupuncture can upregulate GABA expression; another part of how acupuncture helps with pain
  • Norepinephrine (noradrenalin in the UK); another neurotransmitter, the release of which is enhanced by acupuncture. Norepinephrine is also capable of inhibiting pain in the body
  • 5-Hydroxytryptamine (5-HT), or serotonin; is a neurotransmitter that is involved in analgesia (pain relief).  5-HT is secreted in the brain during acupuncture administration, making it another known mechanism of action for acupuncture analgesia
  • Glutamate; a central nervous system neurotransmitter, is involved in the transmission of pain signals in the spinal cord.  Acupuncture downregulates glutamate, as part of how it provides pain relief

Overall a combination of demonstratable mechanisms is clearly at play, and can be seen and measured to be the cause of why acupuncture can help pain. 

How were the studies done?

Research models

Studies on mechanisms of acupuncture analgesia are based on animal models, where levels of neurotransmitters and their effects are measured objectively, removing the possibility of placebo effect as a cause of pain relief. 

Human trials are also used where this is measurable in an ethical and objective way, through fMRI (brain scans showing which areas light up), and blood levels of neurotransmitters as well as pain ratings.

A complicated picture

There are other analgesic mechanisms of acupuncture besides those above, and it is hard to unpick the overall contributions of each, and it may be the case that it depends upon the region targeted, quality of pain and other factors.  For this reason, the acupuncturist’s experience and overall assessment of the individual on the day of treatment contribute to the overall outcome.

Reference:

Zhang, M., Shi, L., Deng, S., Sang, B., Chen, J., Zhuo, B., Qin, C., Lyu, Y., Liu, C., Zhang, J. and Meng, Z., 2022. Effective oriental magic for analgesia: acupuncture. Evidence-Based Complementary and Alternative Medicine, 2022. https://www.hindawi.com/journals/ecam/2022/1451342/

Bibliography:

Li, S.K., Liao, W.D., Zhao, J. and Cao, X.W., 2020. Effects of acupuncture on plasma endogenous opioid peptides in patients with stroke-associated headache in convalescence. Zhen ci yan jiu= Acupuncture Research45(12), pp.995-999.

Lin, J.G., Kotha, P. and Chen, Y.H., 2022. Understandings of acupuncture application and mechanisms. American Journal of Translational Research14(3), p.1469.

Petti, F.., Bangrazi, A., Liguori, A., Reale, G. and Ippoliti, F., 1998. Effects of acupuncture on immune response related to opioid-like peptides. Journal of Traditional Chinese Medicine 18(1), pp.55-63.

Trento, M.M.S., Moré, A.O.O., Duarte, E.C.W. and Martins, D.F., 2021. Peripheral receptors and neuromediators involved in the antihyperalgesic effects of acupuncture: a state-of-the-art review. Pflügers Archiv-European Journal of Physiology473(4), pp.573-593.

Wang, W.S., Xi, H.Y., Fu, G., Fan, X.Z. and Guo, M., 2022. Study on the Mechanism of Electroacupuncture in the Treatment of Neuropathic Pain Based on Vesicular Glutamate Transporter 2/Toll Like Receptor 4 Signal Pathway. Indian Journal of Pharmaceutical Sciences, pp.31-37.

Wu, W.Z., Zheng, S.Y., Liu, C.Y., Qin, S., Wang, X.Q., Hu, J.L., Wan, Q.Y., Zhao, Y.N. and Xi, H.Q., 2021. Effect of Tongdu Tiaoshen acupuncture on serum GABA and CORT levels in patients with chronic insomnia. Zhongguo Zhen jiu= Chinese Acupuncture & Moxibustion41(7), pp.721-724.

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Electro Acupuncture

Electro acupuncture (EA) is an adjunct of acupuncture practise where a small electrical current is passed between pairs of acupuncture needles.  There is usually a slight sensation of buzzing or vibration associated with the electrical pulses, but the procedure is relatively pain free.

EA is a safe and effective form of therapy, which studies and systematic reviews, have shown may benefit patients for the symptoms of a wide range of conditions, in particular:

  • Nausea prevention: post chemotherapy (Zhang et al, 2014); post surgery (Ho et al, 1990); in hyperemesis gravidarum (severe “morning sickness” of pregnancy) (Ezzo et al, 2006);
  • Pain: symptomatic knee pain in rheumatoid arthritis (Casimiro et al 2005); post-operative pain and other recovery benefits post-operatively (Hayhoe, 2010, Lin et al, 2002); labour pain (Qu et al, 2007); low back pain; fibromyalgia (Delize et al. 1992); nerve pain, inflammatory pain and organ pain (Zhang et al, 2014)
  • Dental pain (Tavares et al 2007; Sim et al 2002)
  • Urinary retention after spinal injury (Liu et al 2011); urinary stress incontinence (Zhishun et al, 2017)
  • Tension-type headache (Xue et al, 2004); reducing the frequency of migraine (Xu et al, 2018)
  • Tennis elbow (Yeung et al, 2003); calcific tendonitis (Papadopoulos et al, 2019); achilles tendonitis (Yu et al, 2015)

The acupuncturist may use EA alongside other acupuncture techniques where it is indicated.

References:

Casimiro, L., Barnsley, L., Brosseau, L., Milne, S., Welch, V., Tugwell, P. and Wells, G.A., 2005. Acupuncture and electroacupuncture for the treatment of rheumatoid arthritis. Cochrane Database of Systematic Reviews, (4).

Deluze, C., Bosia, L., Zirbs, A., Chantraine, A. and Vischer, T.L., 1992. Electroacupuncture in fibromyalgia: results of a controlled trial. British Medical Journal305(6864), pp.1249-1252.

Ezzo, J., Streitberger, K. and Schneider, A., 2006. Cochrane systematic reviews examine P6 acupuncture-point stimulation for nausea and vomiting. Journal of Alternative & Complementary Medicine12(5), pp.489-495.

Hayhoe, S., 2010. Postoperative benefits with electroacupuncture. Acupuncture in Medicine28(2), p.64.

Ho, R.T., Jawan, B., Fung, S.T., Cheung, H.K. and Lee, J.H., 1990. Electro‐acupuncture and postoperative emesis. Anaesthesia45(4), pp.327-329.

Lin, J.G., Lo, M.W., Wen, Y.R., Hsieh, C.L., Tsai, S.K. and Sun, W.Z., 2002. The effect of high and low frequency electroacupuncture in pain after lower abdominal surgery. Pain99(3), pp.509-514.

Liu, Z., Liu, Y., Xu, H., He, L., Chen, Y., Fu, L., Li, N., Lu, Y., Su, T., Sun, J. and Wang, J., 2017. Effect of electroacupuncture on urinary leakage among women with stress urinary incontinence: a randomized clinical trial. Jama317(24), pp.2493-2501.

Liu, Z., Zhou, K., Wang, Y. and Pan, Y., 2011. Electroacupuncture improves voiding function in patients with neurogenic urinary retention secondary to cauda equina injury: results from a prospective observational study. Acupuncture in Medicine29(3), pp.188-192.

Papadopoulos, D.V., Koulouvaris, P., Aggelidakis, G., Tsantes, A.G., Mavrodontidis, A. and Papadopoulos, G., 2019. Electroacupuncture for the treatment of supraspinatus calcific tendonitis. Journal of clinical orthopaedics and trauma10(3), pp.624-628.

Qu, F. and Zhou, J., 2007. Electro-acupuncture in relieving labor pain. Evidence-Based Complementary and Alternative Medicine4.

Sim, C.K., Xu, P.C., Pua, H.L., Zhang, G. and Lee, T.L., 2002. Effects of electroacupuncture on intraoperative and postoperative analgesic requirement. Acupuncture in Medicine20(2-3), pp.56-65.

Tavares, M.G., Machado, A.P., Motta, B.G., Borsatto, M.C., Rosa, A.L. and Xavier, S.P., 2007. Electro-acupuncture efficacy on pain control after mandibular third molar surgery. Brazilian Dental Journal18(2), pp.158-162.

Xu, J., Zhang, F.Q., Pei, J. and Ji, J., 2018. Acupuncture for migraine without aura: a systematic review and meta-analysis. Journal of Integrative Medicine16(5), pp.312-321.

Xue, C.C., MApplSc, L.D., Polus, B., English, R.A., Zheng, Z. and Costa, C.D., 2004. Distal point electroacupuncture for tension-type headache (n= 40). Acupuncture in Medicine22(2), pp.103-115.)

Yeung, C.K., Leung, M.C. and Chow, D.H., 2003. The use of electro-acupuncture in conjunction with exercise for the treatment of chronic low-back pain. The Journal of Alternative & Complementary Medicine, 9(4), pp.479-490.

YU, H.L. and XU, L.L., 2015. Therapeutic effect of electro-acupuncture in the treatment of Achilles tendonitis. World Journal of Acupuncture-Moxibustion25(2), pp.17-22.

Zhang, R, Lao, L; Ren, K; Berman, BM (2014) Mechanisms of Acupuncture–Electroacupuncture on Persistent Pain Anesthesiology 2014; 120:482-503

Zhang, X., Jin, H.F., Fan, Y.H., Lu, B., Meng, L.N. and Chen, J.D., 2014. Effects and mechanisms of transcutaneous electroacupuncture on chemotherapy-induced nausea and vomiting. Evidence-Based Complementary and Alternative Medicine2014.

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Robot and Human Hands

Acupuncture and AI?

New Research Paper: Here is an interesting concept for future development in acupuncture: “Artificial intelligence-directed acupuncture: a review”, in the Journal of Chinese Medicine.

How might this work? Wang (2022) and colleagues say that using computing, our ability to quantify, objectify and standardise acupuncture can be increased. Not only this, but using AI perhaps the research and outcomes from published data can be used to identify the best approaches, and even predict treatment outcomes.

It’s worth keeping in mind that from the acupuncturist’s perspective (an usually that of the patient, too), a large part of the appeal of acupuncture as a complementary medicine is that the patient is considered as an individual, and that even for the same condition, the treatment plan can vary from patient to patient as it is tailored to their need, therefore full standardisation is perhaps not the goal here, but more of a case of defining approaches and benefitting from looking at the data in novel ways.

The researchers do say that “The use of AI-based data mining has led to the discovery of hidden knowledge on acupuncture point selection and prescription.” As with any field where there is complexity, it is good to have alternative approaches and paths to choose from, and as practitioners, evidence-led there is always a combination of training and experience, alongside the updates and research insights that come through from the increasing research body.

At the moment the research is focussing on AI for common conditions that have large bodies of data and research for them, e.g. Osteoarthritis of the knee and dysmenorhhoea, and looking at particular pairs and combinations of points that arise in numerous studies.

Other uses for AI to analyse the research and effectiveness have been in the manipulation of needles, which has very many possible forms, including electroacupuncture as an adjunct.

An interesting area, which promises to deliver much insight in the coming years.

If you’d like to look into it more, a few other resources are below, including recent papers from Wang et al (2021), who predict more unified guidelines for specific TCM syndromes to come forth from AI-assisted TCM therapies in the future. Feng et al (2021) also weigh in on the ability to over come subjectivity by using AI; and Alice et al (2021) look into its application to pulse diagnosis in TCM.

References:

Feng, C., Shao, Y., Wang, B., Qu, Y., Wang, Q., Li, Y. and Yang, T., 2021. Development and application of artificial intelligence in auxiliary tcm diagnosis. Evidence-based Complementary and Alternative Medicine2021.

Feng, C., Shao, Y., Wang, B., Qu, Y., Wang, Q., Li, Y. and Yang, T., 2021. Development and application of artificial intelligence in auxiliary tcm diagnosis. Evidence-based Complementary and Alternative Medicine2021.

Wang, Y., Shi, X., Efferth, T. and Shang, D., 2022. Artificial intelligence-directed acupuncture: a review. Chinese Medicine, 17(1), pp.1-10.

Wang, Y., Shi, X., Li, L., Efferth, T. and Shang, D., 2021. The impact of artificial intelligence on traditional Chinese medicine. The American Journal of Chinese Medicine49(06), pp.1297-1314.

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Question Marks

Will acupuncture help me?

Many people ask us as acupuncturists: “What is acupuncture for?  Will it help me?”

There is not a specific list of conditions acupuncture can “treat”, but it can be used safely by the vast majority of patient groups, including during pregnancy, as there are very few contraindications. 

Our Condition Resources Pages provide links to evidence-based factsheets, based on the most commonly requested reasons for attending acupuncture.

A huge number of clinical guidelines now recommend/suggest acupuncture as an approach; most commonly for musculoskeletal, connective tissue, neurological, obstetrics & gynaecology, women’s health, oncology and gastrointestinal issues. (Zhang & al 2022a)

Acupuncture needles in a patient’s back

It is good to read around the research into the symptom or condition you’re looking to address, the factsheets, links and references here on our condition pages are a good place to start, enabling you to find and appraise the original research papers.

Pain

Acupuncture is well-known for use in pain, and is recommended in many countries’ national health services. The NHS body in charge of which treatments should be used in particular conditions recommends acupuncture for chronic pain:  The NICE Scenario Management guidelines (2021) for chronic pain state: “consider a course of acupuncture or dry needling, within a traditional Chinese or Western acupuncture system”. In America, per the US government’s National Institutes of Health: “Clinical practice guidelines issued by the American Pain Society and the American College of Physicians in 2007 recommend acupuncture as one of several nondrug approaches physicians should consider when patients with chronic low-back pain do not respond to self-care (practices that people can do by themselves, such as remaining active, applying heat, and taking pain-relieving medications).”

Popularity with the public, and uptake by insurers

Acupuncture is popular and well established. Per the WHO (2019) global report, acupuncture is widely used across the world, and in the UK, clinicians administer over 4 million acupuncture treatments each year (Zhang et al, 2022b).

Per He et al (2022) in the BMJ “Acupuncture has been incorporated into the health insurance policies of several countries. Studies have indicated that there have been many recommendations for the use of acupuncture in many clinical practice guidelines published worldwide. Both the number of guidelines recommending acupuncture and the number of acupuncture randomised controlled trials (RCTs) are increasing”

Find Out More

Shaftesbury Clinic provides a free 15 minute consultation (in person, videocall or phone call – all need to be pre-booked). This will enable you to weigh up the research, and aid in your decision about acupuncture as a possible complement to medical treatment

The British Acupuncture Council also has a number of resources for you to take a look at, including a 30-minute documentary about acupuncture

Important to know: Chronic health conditions should be addressed under direct medical supervision of your GP or consultant, and acupuncture would be an adjunct complement to usual care – it’s advisable to let your doctor know when you use this approach.

References:

He, Y., Li, J., Li, Y., Jin, R., Wen, Q., Li, N. and Zhang, Y., 2022. Strengthening the quality of clinical trials of acupuncture: a guideline protocol. BMJ open, 12(1), p.e053312. LINK: https://bmjopen.bmj.com/content/12/1/e053312 )

NICE (2021) Chronic pain: Scenario: Management Last revised in April 2021

NIH (2022) https://www.nccih.nih.gov/health/acupuncture-in-depth.

Zhang, Y.Q., Lu, L., Xu, N., Tang, X., Shi, X., Carrasco-Labra, A., Schünemann, H., Chen, Y., Xia, J., Chen, G. and Liu, J., 2022a. Increasing the usefulness of acupuncture guideline recommendations. bmj376. https://bmj.com/content/376/bmj-2022-070533.full

Zhang, Y.Q., Jing, X. and Guyatt, G., 2022b. Improving acupuncture research: progress, guidance, and future directions. BMJ, 376. https://www.bmj.com/content/376/bmj.o487

Helen
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New Research : Acupuncture Tapping in Psychotherapy

A new research article looks at acupuncture points and psychotherapy in practise. The interesting new article in the Journal of Psychotherapy Integration, discusses the use of acupuncture points within psychotherapy (the reference, and links to original article are below).

A holistic approach is increasingly being understood to include more that one modality to increase how effective an approach can be. This is well known for crossing the borders between, say mainstream medicine in areas like pain, but possible less so in the sphere of mental health, despite the fat that acupuncture and TCM (Traditional Chinese Medicine) have long included protocols for health on all levels of mind and body.

Traditional acupuncture uses needle stimulation on a network of specific points, tailored to the patient and presenting condition. In addition to, or instead of needles, acupuncturists can also use heat or acupressure (needle-less stimulation of points).

Tapping of a specific set of points in a protocol, is a fairly ew approach to self-care when experiencing anxiety or pain symptoms, for example. This can be done when the patient has been trained on how to do this, and increasingly this has been adopted in other settings. Today, other techniques incorporate some of the benefits of acupuncture alongside talking therapies, and there is a decent and growing research body here.

Per this research article Feinstein (2022 – ref and link below) the research and use of this are coming to the fore; there are “28 systematic reviews and meta-analyses, 125 clinical trials, 24 case studies, 26 reports describing systematic observations, 17 mixed-method clinical trials that included a tapping component, and 88 articles addressing clinical procedures, theory, mechanisms, or related issues” (Feinstein, 2022).

Sometimes called Emotional Freedom Technique (EFT), this shows the way in which cross-modality approaches can be applicable to real life cases. The acupuncture component of this has indeed been shown to be an active part of EFT (Church et al, 2018).

The overall outcome from looking at the state of research into the integration into psychotherapy of using tapping of acupuncture points is promising, and that the growing evidence base documents the effectiveness, speed, and durability of the approach.

References:

Church, D., Stapleton, P., Yang, A. and Gallo, F., 2018. Is tapping on acupuncture points an active ingredient in Emotional Freedom Techniques? A systematic review and meta-analysis of comparative studies. The Journal of nervous and mental disease206(10), pp.783-793.

Feinstein, D., 2022. Integrating the manual stimulation of acupuncture points into psychotherapy: A systematic review with clinical recommendations. Journal of Psychotherapy Integration. https://psycnet.apa.org/record/2022-61876-001

Helen
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