Important to know: Chronic health conditions should be addressed under direct medical supervision of your GP or consultant, and acupuncture would be an adjunct or complement to usual care – we advise that you let you doctor know when you use this approach.
Acupuncture has been shown to modulate inflammatory responses in the body, as well as to reduce the activity in the areas of the brain associated with pain and stress (as seen on functional MRI brain scans in research settings).
Interpreting the research:
When reading health research, it is important to know that Systematic Reviews or Meta Analyses of a large number of high-quality research studies are the very best way to be able to say to what extent a given treatment can address a condition, symptom, or set of symptoms. The next best level of evidence is the individual Randomised Controlled Study (RCT) which uses a systematic technique to compare two or more groups of patients receiving different treatments (or a treatment against a “control”, or no treatment). In acupuncture trials, the nature of the control group is of particular interest as it is hard to blind a patient to whether they are having a needle inserted or not, and even more challenging to blind the researcher/team to this.
The means and quality of how research is carried out varies considerably from country to country, and in terms of how an intervention is compared to another intervention (or a control). Of note is the fact that “sham” acupuncture (where needles are placed in apparently inert locations rather than traditional acupuncture points) is not really an inert process as it has physiological effects, so that comparing sham and “true acupuncture” may therefore not give a clear picture alone; but and form a part of a research body where acupuncture versus no treatment, vs conventional treatment or vs a different approach/modality also form part of the evidence base.
The n= figure (where quoted in research) tells you how many people were participants in the study, and usually the larger a study (when it is of good quality and design), the more likely it is to be reliable and applicable to larger populations. When (statistical) “significance” is discussed in view of studies it has a very particular meaning – it is the confidence in the data (using statistical tests) that tells us how likely a result could have just come about by chance. The lower the possibility of a chance result, the more likely it is due to the intervention in the experiment. When you are reading a trial/study, the “p” is the number telling us of significance, and this must be under 5% (or p less than 0.05) to mean we can say it is a (statistically) “significant” result.
The research:
Osteoarthritis: Since 2005, there have been over than 50 NHS publications recommending acupuncture for osteoarthritis (largely knee or hip) and many more worldwide (Birch et al 2018).
A large (n=20827) meta-analysis of 39 studies showed acupuncture to be significantly superior to usual care and to sham (non-specific acupuncture point usage), for patients with osteoarthritis and other painful conditions (all p <.001; Vickers et al, 2018). Additionally, clear evidence was found in this meta-study that that the effects of acupuncture persisted over time.
For patients with osteoarthritis pain, acupuncture improved pain relief compared to sham at short-term and at six-month follow up. When compared to wait list controls, acupuncture showed a clinically significant improvement in short term pain relief. A randomised controlled trail in patients with osteoarthritis of the knee or hip, showed a significant difference at three months between acupuncture and routine care (Reinhold et al, 2008; Manheimer et al, 2010).
Knee Pain: Osteoarthritis of the knee is a chronic degenerative disease, with symptoms of pain, stiffness, swelling and dysfunction. OA of the knee is the most prevalent pain- and disability inducing condition in adults over 50 years old (Araya-Quintanilla et al. 2022)
A systematic review and meta-analysis of 17 trials, showed significant benefits whereby in patients in study groups having received acupuncture, this was associated with significantly reduced chronic knee pain 12 weeks (Zhang et al, 2017). Specifically comparing treatments including acupuncture in osteoarthritic knee pain, Corbett et al’s (2013, n=9709) systematic review and network meta-analysis found that acupuncture could be considered as one of the more effective physical treatments for alleviating osteoarthritis knee pain in the short-term: Acupuncture was ranked second out of 21 physical treatments in this study. The team also clarified that further research is also warranted in this area, due to the quality of the research available in some treatment areas across the studies.
Acupuncture can be cost effective, according to an RCT (n=60); acupuncture was offered to patients with knee osteoarthritis who were going to be referred for orthopaedic surgery by their GP, with acupuncture a third were able to avoid surgery which also represented a cost-saving of £100,000 per year [to the NHS]” (White et al, 2016). Acupuncture has been found to improve improve pain and improve function and quality of life in knee osteoarthritis, particularly where chronic (Tian et al, 2022).
An overview of 15 systematic reviews of pain relief in patients with osteoarthritis knee by Araya-Quintanilla et al. (2022) found that in the short term, acupuncture had a moderate positive impact on both pain intensity; and knee function, compared to the control groups. The evidence was rated as low to very low quality according to GRADE ratings.
The systematic review of eleven RCTs with meta-analysis by Tian et al. (2021) found that acupuncture had a positive effect on reducing pain and improving functional activities in patients with knee osteoarthritis. However, there was no significant effect on relieving stiffness or improving the quality of life (mental or physical health) compared to sham acupuncture. The findings suggest that acupuncture can be recommended as a beneficial alternative therapy for patients with chronic pain and knee OA, but further studies are needed to verify the effectiveness in function improvement.
Liu, J., et al, 2022; In this multicentre RCT (n=625), patients were randomly assigned to receive acupuncture at acupoints with Lower Pain Threshold (LPT); acupuncture at acupoints with Higher Pain Threshold (HPT); and no acupuncture (waiting-list group). Measures of pain and symptoms (WOMAC) from baseline to 16 weeks; outcome measures of daily life impact of condition (SF-12 score); and active knee range of motion (ROM) were used as comparators. From baseline to 16 weeks, the effects of acupuncture at acupoints with lower versus higher PT were similar, as both were effective for patients with OA of the knee, “results confirmed the positive effects of acupuncture on pain, stiffness, physical function and quality of life of in patients” compared to the waiting list group.
A further systematic review and meta-analysis is due as per the recent protocol in the BMJ (Lui, C.Y., et al; 2022).
Hip osteoarthritis: There is less research in this area, although it is growing, a systematic review (Manheimer et al, 2018; n=413, for 6 trials) found Acupuncture beneficial as an add-on to usual GP care, with a small but significant benefit for physical quality of life.
Mechanisms of Action:
A review article (Kavoussi & Ross, 2007) suggests that the anti-inflammatory actions that have been demonstrated to be brought about by acupuncture may be mediated via activation of the vagus nerve, alongside deactivation of inflammatory macrophages and other proinflammatory cytokines. The researchers concluded that “The use of acupuncture as an adjunct therapy to conventional medical treatment for a number of chronic inflammatory and autoimmune diseases seems plausible and should be validated by confirming its cholinergicity”. Other studies (Zijlstra et al, 2003) have revealed that acupuncture some of the pain modulating and anti-inflammatory effects exhibited in acupuncture may be due to the fact that it has been shown to stimulate certain substances in the body which act as vasodilators, neurotransmitters and painkillers (beta-endorphins, CGRP and substance P) and further stimulate cytokines and nitric oxide, all of which play roles in inflammatory states.
Zijlstra et al (2003) reviewed the effects and mechanisms of acupuncture in treating various inflammatory diseases and conditions. They proposed the mechanisms of action:
✳️ Acupuncture may release neuropeptides from nerve endings that have vasodilative and anti-inflammatory effects through CGRP.
✳️ Acupuncture may also interact with substance P, which is involved in pain transmission and inflammation.
✳️ Acupuncture may contribute to analgesia by stimulating the release of β-endorphin, which binds to opioid receptors and inhibits pain signals.
✳️ Acupuncture may influence the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines such as TNF-α and IL-10.
CSR and ERP are blood tests related to the functioning of the immune system, that can measure and monitor inflammation in the body. They are relevant to conditions such as Rheumatoid Arthritis, and other immune and inflammatory conditions. Per a review by Feng at al, (2023) electroacupuncture (EA) plus medication had a significant effect in lowering both ESR and CRP levels in patients with RA compared with medication alone. These results suggest that EA may have an anti-inflammatory effect and improve the immune status of patients with RA.
Liu et al (2014) investigated the anti-inflammatory effect of electroacupuncture (EA) in a rat tissue chamber model of inflammation. The study found that EA inhibited the p65 protein from moving to the cell nucleus to activate inflammatory genes. EA also increased the expression of IκBα, which binds to NF-κB and preventing it from entering the nucleus to activate inflammatory genes. These interfere with the IκB/NF-κB pathway that regulates inflammation, indicating one of the mechanisms of acupuncture in modulating immune / inflammatory response.
Acupuncture stimulates the body to create its own natural painkilling substances, such as Beta Endorphins (β-Endorphin). In studies acupuncture has been shown to stimulate the production of natural painkillers called opioid-like peptides (OLPs), including β-Endorphin: For example, this was shown in an RCT in 90 patients with a range of painful disorders (Petti et al, 1998). The same study showed acupuncture also and enhanced the activity of immune cells (lymphocytes, natural killer cells and monocytes) that help fight infections and diseases (Petti et al, 1998).
Acupuncture can activate mast cells at acupoints, which release histamine, serotonin, adenosine, and other mediators that modulate nerve transmission and inflammation (Li et al, 2022)
Wang et al (2023) reviewed evidence from animal and human studies regarding the immunomodulatory mechanism of acupuncture, regarding its effects on different components of the immune system, such as mast cells, macrophages, neutrophils, natural killer cells, astrocytes, microglia, CD4+ and CD8+ T cells, and cytokines. They detailed the neuroanatomical mechanisms of acupuncture in immunomodulation, such as the vagal-adrenal pathway, the cholinergic anti-inflammatory pathway, the spinal sympathetic pathway, the brain-gut axis, and the hypothalamus-pituitary-adrenal axis. They concluded that studies to support the role of acupuncture in regulating inflammation, infection, allergy, pain, and tissue repair.
Per MacDonald et al (2015), acupuncture may:
- modulate immune function by altering the balance of Th1 and Th2 cells and suppressing mast cell degranulation
- influence various receptors and signalling pathways that are involved in inflammatory response, such as TRPV1, opioid, chemokine, dopamine, and cannabinoid receptors
- activate a novel cholinergic anti-inflammatory pathway that involves vagal and sciatic nerves and is mediated by dopamine
- reduce inflammation by downregulating proinflammatory neuropeptides, cytokines, and neurotrophins
Animal Models
Many mechanisms of action have been investigated in animal models as well as in humans to measure brain activity associated with pain and the levels of biomarkers associated with inflammation.
Animal models: A systematic review and meta-analysis of 21 animal studies (Yu et al, 2023) investigated acupuncture’s effect on pain and swelling of arthritis animal models. Acupuncture was found to increase tolerance to pain stimuli and reduce swelling in arthritis animals, the researchers suggested possible mechanisms of action as being via nervous and immune system regulation.
An animal model study (Sun et al, 2023; n=36) investigated the effects of electroacupuncture (EA) on rheumatoid arthritis (RA) in rats, plus its underlying mechanisms. They showed that acupuncture helped RA outcome measures of paw oedema, pain responses, serum cytokines, synovial inflammation, in collagen-induced arthritis (CIA) rats. They were able to show that RA worked by blocking a pathway in the synovium called TLR2/4, that activates immune response and inflammation. The researchers therefore suggested the anti-inflammatory and analgesic effects of EA were related to the inhibition of TLR2/4 signalling on synovial fibroblasts and macrophages.
Electroacupuncture (EA) has been shown in a rat model (Li et al, 2008) to have anti-inflammatory benefits by modulating the hypothalamic-pituitary-adrenal (HPA) axis, (HPA axis regulates the stress response and immune function). Specifically, Li et al outlined that EA sets off a cascade in the brain (via corticotropin-releasing hormone, and adrenocorticotropic hormone) to produce cortisol, which reduces inflammation and oedema.
You may also find this useful: our Rheumatoid Arthritis page
Resources
BAcC Osteoarthritis of the Knee Factsheet
Evidence Based Acupuncture Foundation Osteoarthritis Evidence Summary
References:
Araya-Quintanilla, F., Cuyúl-Vásquez, I. and Gutiérrez-Espinoza, H., 2022. Does acupuncture provide pain relief in patients with osteoarthritis knee? An overview of systematic reviews. Journal of Bodywork and Movement Therapies, 29, pp.117-126.
Birch, S., Lee, M.S., Alraek, T. and Kim, T.H., 2018. Overview of treatment guidelines and clinical practical guidelines that recommend the use of acupuncture: a bibliometric analysis. The Journal of Alternative and Complementary Medicine, 24(8), pp.752-769.
Corbett, M.S., Rice, S.J.C., Madurasinghe, V., Slack, R., Fayter, D.A., Harden, M., Sutton, A.J., Macpherson, H. and Woolacott, N.F., 2013. Acupuncture and other physical treatments for the relief of pain due to osteoarthritis of the knee: network meta-analysis. Osteoarthritis and cartilage, 21(9), pp.1290-1298.
Feng, Y., Zhang, R., Zhao, Z., He, Y., Pang, X., Wang, D. and Sun, Z., 2023. Efficacy and safety of electroacupuncture combined with medication for rheumatoid arthritis: A systematic review and meta-analysis. Heliyon.
Kavoussi B, Ross BE. The neuroimmune basis of anti-inflammatory acupuncture. Integr Cancer Ther 2007; 6: 251-7.
Li, A., Lao, L., Wang, Y., Xin, J., Ren, K., Berman, B.M., Tan, M. and Zhang, R., 2008. Electroacupuncture activates corticotrophin-releasing hormone-containing neurons in the paraventricular nucleus of the hypothalammus to alleviate edema in a rat model of inflammation. BMC Complementary and Alternative Medicine, 8(1), pp.1-8.
Li, Y., Yu, Y., Liu, Y. and Yao, W., 2022. Mast cells and acupuncture analgesia. Cells, 11(5), p.860.
Liu, J., Li, Y., Li, L., Luo, X., Li, N., Yang, X., Zhang, H., Liu, Z., Kang, D., Luo, Y. and Liu, Y., 2022. Effects of acupuncture at acupoints with lower versus higher pain threshold for knee osteoarthritis: a multicenter randomized controlled trial. Chinese Medicine, 17(1), pp.1-12.
Liu, F., Fang, J., Shao, X., Liang, Y., Wu, Y. and Jin, Y., 2014. Electroacupuncture exerts an anti-inflammatory effect in a rat tissue chamber model of inflammation via suppression of NF-κB activation. Acupuncture in Medicine, 32(4), pp.340-345.
Liu, C.Y., Tu, J.F., Lee, M.S., Qi, L.Y., Yu, F.T., Yan, S.Y., Li, J.L., Lin, L.L., Hao, X.W., Su, X.T. and Yang, J.W., 2022. Is acupuncture effective for knee osteoarthritis? A protocol for a systematic review and meta-analysis. BMJ open, 12(1), p.e052270.
McDonald, J.L., Cripps, A.W. and Smith, P.K., 2015. Mediators, receptors, and signalling pathways in the anti-inflammatory and antihyperalgesic effects of acupuncture. Evidence-Based Complementary and Alternative Medicine, 2015.
Manheimer E, Cheng K, Linde K, Lao L, Yoo J, Wieland S, et al. Acupuncture for peripheral joint osteoarthritis. Cochrane Database of Systematic Reviews 2010, Issue 1.
Manheimer, E., Cheng, K., Wieland, L.S., Shen, X., Lao, L., Guo, M. and Berman, B.M., 2018. Acupuncture for hip osteoarthritis. Cochrane Database of Systematic Reviews, (5).
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.
Reinhold T, Witt CM, Jena S, Brinkhaus B, Willich SN. Quality of life and cost-effectiveness of acupuncture treatment in patients with osteoarthritis pain. Eur J Health Econ 2008;9(3):209-19.
Sun, S.Y., Yan, Q.Q., Qiao, L.N., Shi, Y.N., Tan, L.H. and Yang, Y.S., 2023. Electroacupuncture Alleviates Pain Responses and Inflammation in Collagen-Induced Arthritis Rats via Suppressing the TLR2/4-MyD88-NF-κB Signaling Pathway. Evidence-Based Complementary and Alternative Medicine, 2023.
Tian, H., Huang, L., Sun, M., Xu, G., He, J., Zhou, Z., Huang, F., Liu, Y. and Liang, F., 2022. Acupuncture for Knee Osteoarthritis: A Systematic Review of Randomized Clinical Trials with Meta-Analyses and Trial Sequential Analyses. BioMed Research International, 2022.
Vickers, A.J., Vertosick, E.A., Lewith, G., MacPherson, H., Foster, N.E., Sherman, K.J., Irnich, D., Witt, C.M., Linde, K. and Acupuncture Trialists’ Collaboration, 2018. Acupuncture for chronic pain: update of an individual patient data meta-analysis. The Journal of Pain, 19(5), pp.455-474.
Wang, M., Liu, W., Ge, J. and Liu, S., 2023. The immunomodulatory mechanisms for acupuncture practice. Frontiers in Immunology, 14.
White, A., Tough, L., Eyre, V., Vickery, J., Asprey, A., Quinn, C., Warren, F., Pritchard, C., Foster, N.E., Taylor, R.S. and Underwood, M., 2016. Western medical acupuncture in a group setting for knee osteoarthritis: results of a pilot randomised controlled trial. Pilot and feasibility studies, 2(1), pp.1-8.
Yu, W.L. and Kim, S.N., 2023. The effect of acupuncture on pain and swelling of arthritis animal models: A systematic review and meta-analysis. Frontiers in Genetics, 14.
Zhang, Q., Yue, J., Golianu, B., Sun, Z. and Lu, Y., 2017. Updated systematic review and meta-analysis of acupuncture for chronic knee pain. Acupuncture in Medicine, 35(6), pp.392-403.
Zijlstra, F.J., van den Berg-de Lange, I., Huygen, F.J. and Klein, J., 2003. Anti-inflammatory actions of acupuncture. Mediators of inflammation, 12(2), pp.59-69.