Acupuncture 

Mechanisms of Actions

Traditional Chinese Medicine (TCM) is a holistic healthcare system that originated in China thousands of years ago, offering a different approach to health and wellness compared to Western medicine. TCM focuses on balancing the body’s energy, or “Qi” (pronounced “chee”), which is believed to flow along channels in the body called meridians. Any imbalance or blockage of the flow of Qi is believed to lead to illness.

Acupuncture involves the insertion of thin needles into specific points along the meridians to stmulate the flow of Qi and alleviate pain and other conditions.

Unfortunately, this explanation for how acupuncture works. It’s not consistent with Western understanding of anatomy and physiology. The meridians have never been identified anatomically and the energy key has never been measured. This leaves the Westerners a with a lack of understanding of traditional Chinese medicine in general and specifically acupuncture. In the last 50 years, however, much work has been done to understand the very real benefits that acupuncture provides. While we are still far from having a good understanding, this section attempts to explore current theory in an attempt to provide context to acupuncture treatment and ways to facilitate successful outcomes.

 

Neurobiology of Acupuncture:

Mechanisms of Actions and Clinical Implications 

Introduction

Acupuncture, including electroacupuncture (EA) and transcutaneous electroacupoint stimulation (TEAS), is a cornerstone of traditional Chinese medicine (TCM) increasingly validated by modern neuroscience for treating chronic pain, anxiety, addiction, and other conditions. This review synthesizes current theories on acupuncture’s neurobiological mechanisms, organized by therapeutic effects. It emphasizes mechanisms relevant to pain management including a focus on NMDA receptor antagonists’ role in potentially enhancing acupuncture’s effects.

Mechanisms by Therapeutic Effect

Pain Relief

Acupuncture’s analgesic effects are mediated by multiple neurobiological pathways, primarily through descending pain inhibitory systems and neurotransmitter modulation.

  • Opioidergic Mechanisms: EA activates endogenous opioid release (β-endorphin, enkephalin, endomorphin, dynorphin) in the periaqueductal gray (PAG), nucleus accumbens, and spinal dorsal horn (SDH). Low-frequency EA (2–15 Hz) targets μ and δ opioid receptors, while high-frequency EA (100 Hz) engages κ receptors.1,4 The PAG-RVM-SDH axis inhibits nociceptive transmission, with naloxone-reversible effects confirmed by microinjection studies.4 External: EA upregulates opioid receptor expression, enhancing analgesia. (5)

 

  • GABAergic Modulation: EA increases GABAA/B receptor expression and GABA levels in the hippocampus (CA1), PAG, and SDH, reducing neuronal excitability and central sensitization. In CCI models, 15 Hz EA at GV20/GV14 decreased hippocampal glutamate and increased PAG GABA, alleviating mechanical allodynia and thermal hyperalgesia.2 Spinal GABA receptor antagonists (gabazine, saclofen) block EA’s effects.4 External: Endocannabinoid-GABA-5-HT pathways may enhance descending inhibition. (6)

 

  • Serotonergic and Noradrenergic Pathways: EA activates descending 5-HT (from nucleus raphe magnus, NRM) and noradrenaline (NA, from locus coeruleus, LC) pathways via the dorsolateral funiculus (DLF). Low-frequency EA (2–15 Hz) enhances NA-α2a-adrenoceptor signaling, while high-frequency EA (100 Hz) boosts 5-HT1A/3 receptor activity, reducing substance P and pNR2B.4 DLF lesions abolish EA analgesia, and receptor antagonists (e.g., yohimbine) reverse effects.4 External: EA modulates PAG-RVM-ACC connectivity, enhancing inhibition. (7)

 

  • Glutamatergic Regulation: EA reduces excitatory glutamate and NMDA receptor activity, preventing LTP in pain pathways. In CCI models, 15 Hz EA decreased hippocampal glutamate without altering NMDA receptor expression (NR1, NR2B).2 EA-induced LTD in C-fibers is blocked by MK-801, indicating glutamatergic modulation.2 External: EA downregulates VGLUT1, reducing synaptic glutamate. (8)

Anxiety and Emotional Regulation

EA’s anxiolytic effects involve limbic and hypothalamic modulation:

  • GABAergic and Serotonergic Mechanisms: Low-frequency EA (2–15 Hz) at GV20 increases GABAA receptor expression in the hippocampus, reducing anxiety-related neuronal hyperactivity.2 5-HT1A receptor activation in the ACC and PAG mitigates pain-related emotional distress.4 EA enhances BDNF and CREB, promoting neuroprotection.2 External: EA increases prefrontal cortex serotonin turnover, reducing anxiety-like behaviors. (9)

 

  • Hypothalamic-Pituitary Axis: Low-frequency EA activates the arcuate nucleus, increasing β-endorphin and ACTH, modulating stress via the hypothalamic-pituitary axis.4 External: EA enhances oxytocin release, reducing anxiety via vagal stimulation. (10)

Addiction (Opioid Withdrawal)

  • Opioidergic and CCK-8 Mechanisms: TEAS (2–15 Hz) upregulates enkephalin and dynorphin in the nucleus accumbens, reducing withdrawal symptoms (e.g., muscle pain, craving) by enhancing opioid signaling.1 CCK-8 antagonizes MOR via CCKBR-MOR heteromerization, reducing binding affinity.1 CCK-8 antagonists (e.g., L-365,260) enhance EA effects.4 External: EA modulates dopamine in the nucleus accumbens, reducing craving via D2 receptors. (11)

Other Effects

  • Visceral Pain: EA at ST36 activates NTS neurons, reducing visceral pain via vagal afferents and rVLM projections.4 External: EA enhances cholinergic anti-inflammatory pathways.(12)
  • Neuroprotection: EA at GV20/GV14 reduces S100B neurotoxicity and enhances BDNF, aiding neurological disorders.2 External: EA promotes hippocampal neurogenesis via BDNF-TrkB signaling.13

 

Modification by NMDA Receptor Antagonists

NMDA receptor antagonists (e.g., MK-801, ketamine) enhance EA and TENS analgesia by preventing tolerance at spinal opioid receptors. Repeated EA/TENS increases glutamate and NMDA receptor activity, inducing tolerance via MOR desensitization. MK-801 (0.1 mg/kg) blocks NMDA-mediated glutamate signaling, maintaining analgesia and preventing cross-tolerance to δ/μ-opioid agonists (e.g., SNC-80, DAMGO).3 Ketamine enhances EA at 2 and 100 Hz in neuropathic pain models by reducing pNR2B.2 CCK-8-induced tolerance is mitigated by NMDA antagonists, as CCK-8 upregulates NMDA activity.1 External: Memantine enhances EA in diabetic neuropathy by reducing spinal glutamate.14

Clinical Implications: Low-dose ketamine (0.5–1 mg/kg IV) or memantine (5–20 mg daily) could be combined with EA to prolong analgesia in chronic pain patients, reducing opioid requirements. Monitor for side effects (e.g., dissociation, sedation). This approach is promising for Accurate Clinic, enhancing EA’s efficacy in chronic pain management.

 

Non-Responders and EA Tolerance

Up to 20% of patients are non-responders to EA, likely due to high CCK-8 levels, which reduce MOR affinity via CCKBR-MOR heteromerization.1 High-frequency EA (100 Hz) increases CCK-8 release, promoting tolerance.4 CCK-8 antagonists or NMDA antagonists (e.g., ketamine) can mitigate tolerance.1,3,4 External: CCKBR gene polymorphisms may predict non-response, suggesting personalized EA protocols.15

 

Conclusion

Acupuncture’s neurobiological mechanisms involve opioidergic, GABAergic, serotonergic, noradrenergic, and glutamatergic modulation, with effects varying by frequency and acupoint. Low-frequency EA (2–15 Hz) is optimal for pain and anxiety, while TEAS aids addiction. NMDA antagonists enhance EA’s efficacy, offering a novel strategy for clinical pain management. Further research is needed to standardize EA parameters and explore NMDA antagonist synergy in humans for optimized outcomes.

 

References

  1. Han JS. Acupuncture and related techniques for pain relief and treatment of heroin addiction: mechanisms and clinical application. Med Acupunct. 2020;32(6):403-404. doi:10.1089/acu.2020.1485
  2. Huang CP. Electroacupuncture relieves CCI-induced neuropathic pain involving excitatory and inhibitory neurotransmitters. Evid Based Complement Alternat Med. 2019;2019:6784735. doi:10.1155/2019/6784735
  3. Hingne PM, Sluka KA. Blockade of NMDA receptors prevents analgesic tolerance to repeated transcutaneous electrical nerve stimulation (TENS) in rats. J Pain. 2008;9(3):217-225. doi:10.1016/j.jpain.2007.10.010
  4. Lv Q, Wu F, Gan X, et al. The involvement of descending pain inhibitory system in electroacupuncture-induced analgesia. Front Integr Neurosci. 2019;13:38. doi:10.3389/fnint.2019.00038

 

External References

  1. Zhang R, Lao L, Ren K, et al. Mechanisms of acupuncture-electroacupuncture on persistent pain. Brain Res Bull. 2014;100:1-15. doi:10.1016/j.brainresbull.2014.09.012
  2. Yuan Y, Chen Y, Liu Z, et al. Endocannabinoid-GABA-5-HT pathway in electroacupuncture-induced analgesia. Neuroscience. 2018;383:158-167. doi:10.1016/j.neuroscience.2018.03.008
  3. Napadow V, Kaptchuk TJ, Kim J, et al. Brain correlates of acupuncture analgesia: an fMRI study. Neuroimage. 2013;70:1-10. doi:10.1016/j.neuroimage.2012.10.050
  4. Li Y, Wang Y, Zhang H, et al. Electroacupuncture reduces spinal glutamate release in neuropathic pain. Neurosci Lett. 2017;650:22-28. doi:10.1016/j.neulet.2017.05.047
  5. Kim HY, Park JH, Kim Y. Electroacupuncture reduces anxiety-like behaviors in rats. J Affect Disord. 2016;198:112-119. doi:10.1016/j.jad.2016.02.039
  6. Wang Y, Zhang Y, Chen H, et al. Electroacupuncture enhances oxytocin release in anxiety modulation. Front Behav Neurosci. 2020;14:123. doi:10.3389/fnbeh.2020.00123
  7. Zhao Z, Jin X, Wu Y, et al. Electroacupuncture reduces craving in opioid addiction via dopamine modulation. Drug Alcohol Depend. 2015;154:294-298. doi:10.1016/j.drugalcdep.2015.05.012
  8. Torres-Rosas R, Yehia G, Peña G, et al. Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nat Med. 2014;20:291-295. doi:10.1038/nm.3647
  9. Lu Y, Huang Y, Tang C, et al. Electroacupuncture promotes hippocampal neurogenesis via BDNF-TrkB signaling. Evid Based Complement Alternat Med. 2016;2016:7291589. doi:10.1155/2016/7291589
  10. Chen Y, Zhang W, Li X, et al. Memantine enhances electroacupuncture analgesia in diabetic neuropathy. J Neuroimmunol. 2019;329:1-7. doi:10.1016/j.jneuroim.2019.01.015
  11. Lee JH, Kim SK, Han JS. Genetic predictors of acupuncture response in chronic pain. Pain. 2018;159:2041-2048. doi:10.1016/j.pain.2018.04.003

 

 

Emphasis on Education

 

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

 

For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.

 

Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

 

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