Acupuncture for Pain Management: Mechanisms and Protocols

The Evidence Base

Pain management is where acupuncture meets Western medicine most convincingly. The evidence is robust, the mechanisms are increasingly well-understood, and the clinical outcomes are documented in multiple high-quality meta-analyses.

The landmark study was Vickers et al. (2012, Archives of Internal Medicine/JAMA Internal Medicine) — an individual patient data meta-analysis pooling data from 29 randomized controlled trials with 17,922 patients. This was not a standard meta-analysis of published results; the researchers obtained raw data from each trial and reanalyzed it with consistent methodology. Their conclusions:

1. Acupuncture is effective for chronic pain (back pain, neck pain, osteoarthritis, headache) — superior to both sham acupuncture and no-acupuncture controls.
2. The effect sizes were clinically meaningful — not merely statistically significant but large enough to make a real difference in patients’ lives.
3. The difference between real and sham acupuncture, while smaller than the difference between real acupuncture and no treatment, was statistically significant — indicating that specific needling effects (not just placebo or contextual effects) contribute to the outcome.

Vickers et al. updated this analysis in 2018 (Journal of Pain), adding data from 20,827 additional patients across 10 new trials, confirming the original findings with even greater statistical power. The effect persisted at 12-month follow-up, arguing against a purely psychological explanation.

MacPherson et al. (2017, Journal of Pain) further demonstrated that acupuncture’s effects for chronic pain are maintained at one year, with only a 15% reduction in effect size — comparable to the persistence of pharmaceutical analgesic effects and superior to the rapid fade seen with many placebo interventions.

Mechanisms of Action: Why Acupuncture Works for Pain

1. Gate Control Theory

Melzack and Wall’s gate control theory of pain (1965, Science) proposed that stimulation of large-diameter A-beta afferent nerve fibers (touch, pressure) inhibits the transmission of pain signals carried by small-diameter A-delta and C fibers at the dorsal horn of the spinal cord. The “gate” is a neural circuit in the substantia gelatinosa of the spinal dorsal horn that modulates pain signal transmission to the brain.

Acupuncture needles, when inserted into tissue and manipulated, activate A-beta and A-delta afferents through mechanical stimulation of tissue mechanoreceptors and free nerve endings. This provides “gate” input that inhibits pain signal transmission — explaining the immediate (though often temporary) analgesic effect of acupuncture.

The gate control mechanism is fast-acting (seconds to minutes), somatotopically organized (needling near the pain source is most effective for this mechanism), and is the primary mechanism for local and segmental acupuncture analgesia.

2. Endogenous Opioid Release

The discovery that acupuncture triggers the release of endogenous opioid peptides was one of the most important breakthroughs in acupuncture research. Beginning with the work of Han Ji-Sheng in the 1970s-1990s at Peking University, a clear picture has emerged:

• Low-frequency stimulation (2-4 Hz): Preferentially releases beta-endorphin and enkephalin — mu-opioid receptor agonists. These produce a deep, slow-onset, long-lasting analgesia, with effects persisting hours after treatment. The analgesic effect is blocked by naloxone (an opioid antagonist), confirming the opioid mechanism (Mayer et al., 1977, Brain Research).
• High-frequency stimulation (80-100 Hz): Preferentially releases dynorphin — a kappa-opioid receptor agonist. This produces a faster onset, shorter duration analgesia with different quality.
• Alternating frequency (2/100 Hz): Han’s research demonstrated that alternating between low and high frequencies produces a synergistic analgesic effect greater than either frequency alone, by simultaneously activating mu, delta, and kappa opioid receptors and preventing tolerance development. This “dense-dispersive” (DD) mode is widely used in electroacupuncture protocols.

The opioid mechanism explains several clinical observations:

• Acupuncture analgesia builds over successive treatments (progressive sensitization of opioid pathways)
• Tolerance can develop with daily treatment (opioid receptor downregulation — spacing treatments every 2-3 days is often more effective than daily)
• Acupuncture is more effective in some individuals than others (genetic variation in opioid receptor density and endorphin production)

3. Adenosine/Purinergic Signaling

Goldman et al. (2010, Nature Neuroscience) published a landmark paper demonstrating a novel peripheral mechanism for acupuncture analgesia. They showed that:

• Acupuncture needle rotation at the point ST-36 in mice caused a 24-fold increase in extracellular adenosine concentration in the tissue surrounding the needle.
• Adenosine activated A1 adenosine receptors on local nociceptive (pain-sensing) nerve endings, inhibiting their activity.
• The analgesic effect was eliminated in A1 receptor knockout mice, confirming the specificity of the mechanism.
• Deoxycoformycin, a drug that inhibits adenosine degradation (adenosine deaminase inhibitor), dramatically enhanced and prolonged acupuncture analgesia by extending the duration of elevated adenosine levels.

This finding provided the first mechanistic explanation for why manual needle manipulation (producing tissue micro-damage and ATP release, which is metabolized to adenosine) is required for analgesia — simply inserting a needle without manipulation (as in minimal/sham acupuncture) produces less ATP release and therefore less adenosine.

4. Descending Inhibitory Pathways

The periaqueductal gray (PAG) — a brainstem structure surrounding the cerebral aqueduct in the midbrain — is the master control center for descending pain inhibition. When activated, the PAG sends projections to the rostral ventromedial medulla (RVM), which then sends descending fibers through the dorsolateral funiculus of the spinal cord to inhibit pain transmission at the dorsal horn.

fMRI studies have demonstrated that acupuncture activates the PAG and related brainstem nuclei. Napadow et al. (2005, NeuroImage) showed that acupuncture at LI-4 (Hegu) and ST-36 (Zusanli) produced significant activation of the hypothalamus, PAG, and rostral anterior cingulate cortex — all components of the descending inhibitory pathway.

This mechanism provides the basis for distal point analgesia — why needling a point on the hand (LI-4) can relieve headache pain, or needling the foot (LR-3) can relieve pain anywhere along the Liver meridian. The signal from the peripheral needle insertion travels to the brainstem, activates the descending inhibitory system, and suppresses pain processing at the spinal level — a central, not local, mechanism.

5. Anti-Inflammatory Mechanisms

Chronic pain involves neuroinflammation — the sustained release of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6), prostaglandins, and nerve growth factor in damaged or sensitized tissues. These inflammatory mediators sensitize nociceptors (peripheral sensitization) and alter spinal cord processing (central sensitization), converting acute pain into chronic pain.

Acupuncture has demonstrated anti-inflammatory effects through multiple pathways:

• Vagal anti-inflammatory pathway: Electroacupuncture at ST-36 activates vagal afferents that project to the nucleus tractus solitarius (NTS) in the brainstem, which then activates the efferent vagal cholinergic anti-inflammatory pathway — suppressing TNF-alpha production by macrophages through alpha-7 nicotinic acetylcholine receptors (Torres-Rosas et al., 2014, Nature Medicine). (See also: acupuncture-autoimmune-modulation.md)
• Local anti-inflammatory effects: Adenosine (released at the needle site) has anti-inflammatory properties through A2A receptor activation on immune cells. Acupuncture also modulates mast cell degranulation and local prostaglandin release.
• Cortisol modulation: Acupuncture can modulate the HPA axis, influencing cortisol levels — the body’s primary endogenous anti-inflammatory hormone.

6. Central Sensitization Reversal

In chronic pain states, the spinal cord and brain undergo neuroplastic changes — wind-up, long-term potentiation at dorsal horn synapses, glial cell activation, altered descending modulation — that amplify pain signals and maintain pain even after the original tissue injury has healed. This is “central sensitization” — the nervous system itself has become the disease.

Acupuncture has shown efficacy in reversing central sensitization through:

• Modulation of NMDA receptor activity at the spinal dorsal horn (Huang et al., 2002, Neuroscience Letters)
• Reduction of spinal glial cell activation (Shan et al., 2019)
• Restoration of descending inhibitory tone from the PAG/RVM
• Normalization of cortical pain processing (demonstrated by fMRI normalization of pain network activity)

This is why acupuncture is often effective for chronic pain conditions that have failed pharmaceutical management — it addresses the central nervous system component that drugs targeting peripheral inflammation (NSAIDs) or peripheral nerve conduction (local anesthetics) cannot reach.

Clinical Protocols

Chronic Low Back Pain

Low back pain (LBP) is the most studied indication for acupuncture, with strong evidence from multiple systematic reviews and meta-analyses (Vickers 2012, 2018; Qaseem et al., 2017, Annals of Internal Medicine — ACP clinical practice guideline recommending acupuncture as first-line treatment for chronic LBP).

Primary Points:

• BL-23 (Shenshu): Kidney Back-Shu point. Located 1.5 cun lateral to the lower border of L2 spinous process. Tonifies the Kidney, strengthens the lower back. Used bilaterally.
• BL-25 (Dachangshu): Large Intestine Back-Shu point. 1.5 cun lateral to L4 spinous process. Regulates the lower back and intestines.
• BL-40 (Weizhong): He-Sea point of the Bladder meridian. Center of the popliteal crease. “For back pain, seek Weizhong” — classical dictum. Distal point that activates the descending inhibitory pathway for the entire Bladder meridian (which traverses the entire spine).
• GV-3 (Yaoyangguan): On the midline at L4. Strengthens the lower back and knees, warms Kidney Yang.
• GV-4 (Mingmen): On the midline at L2 (between the kidneys). Gate of Vitality — tonifies Kidney Yang, warms the lower back.
• BL-60 (Kunlun): Between the lateral malleolus and Achilles tendon. Powerful distal point for back pain, relaxes the sinew channel.

Ashi Points: Tender points at the site of maximum pain — these are needled directly for local analgesic effect (gate control, adenosine release).

Electroacupuncture Parameters: 2/100 Hz alternating frequency, 0.5-2.0 mA (to patient tolerance), 20-30 minutes. Applied between BL-23 and BL-25 (or across the area of maximum pain).

Treatment Frequency: 2x/week for 4-6 weeks initially (10-12 sessions), then weekly for 4 weeks, then monthly maintenance if needed. Response is typically seen by session 4-6; if no improvement by session 8-10, reassess diagnosis.

Headache and Migraine

Acupuncture for migraine prophylaxis is supported by Cochrane reviews (Linde et al., 2016), which concluded that acupuncture is at least as effective as prophylactic drug treatment and has fewer side effects. The NNT (number needed to treat) for acupuncture to prevent one migraine attack is approximately 4 — comparable to topiramate and superior to most prophylactic pharmaceuticals.

Primary Points:

• LI-4 (Hegu): The master point for the face and head. Located in the first dorsal interosseous muscle between the thumb and index finger. Analgesic, anti-inflammatory, activates the descending inhibitory pathway.
• LR-3 (Taichong): Paired with LI-4 as the “Four Gates” (Si Guan) — a classical protocol for moving Qi throughout the body, calming the Liver, and relieving head pain. Located between the 1st and 2nd metatarsals.
• GB-20 (Fengchi): At the base of the skull, in the depression between the sternocleidomastoid and trapezius muscles. Releases the occiput, disperses Wind (acute headache trigger), relieves the eyes and head.
• GV-20 (Baihui): On the vertex of the skull. Clears the mind, lifts Yang, treats vertex headache and dizziness.
• Taiyang (Extra Point): Temple region. Local point for temporal headache/migraine.
• Yintang (Extra Point): Between the eyebrows. Calms the Shen, treats frontal headache.
• GB-8 (Shuaigu): Above the ear apex. Specific for temporal/migraine headache.

Pattern Differentiation:

• Liver Yang Rising migraine (throbbing, temporal, worse with stress/anger): Add LR-2 (Xingjian), GB-34 (Yanglingquan), GB-43 (Xiaxi). Sedate Liver, descend Yang.
• Blood Deficiency headache (dull, worse with fatigue, better lying down): Add ST-36 (Zusanli), SP-6 (Sanyinjiao), BL-17 (Geshu). Tonify Blood, nourish the head.
• Phlegm-Dampness headache (heavy, cloudy, worse in humid weather): Add ST-40 (Fenglong), SP-9 (Yinlingquan), CV-12 (Zhongwan). Resolve Phlegm, dry Dampness.
• Kidney Deficiency headache (empty, dull, vertex, worse with overwork): Add KI-3 (Taixi), KI-7 (Fuliu), GV-20 (Baihui). Tonify Kidney, fill the Sea of Marrow.

Treatment Frequency for Migraine Prophylaxis: 1-2x/week for 8 weeks (12-16 sessions minimum). Linde et al. (2016) found that at least 12 sessions over 8 weeks was the typical protocol in effective trials. Effects typically build over the course of treatment and persist for 3-6 months after discontinuation.

Fibromyalgia

Fibromyalgia — characterized by widespread pain, fatigue, sleep disturbance, and cognitive dysfunction — is a central sensitization disorder. The nervous system amplifies pain signals globally. This makes it an ideal indication for acupuncture, which addresses central sensitization through multiple mechanisms.

Deare et al. (2013, Cochrane Database of Systematic Reviews) reviewed acupuncture for fibromyalgia and found moderate-quality evidence for pain reduction with electroacupuncture, with effects persisting for at least one month post-treatment.

Primary Points:

• LI-4 (Hegu) + LR-3 (Taichong): Four Gates — global Qi regulation
• ST-36 (Zusanli): Tonifies Qi and Blood, regulates the immune system
• SP-6 (Sanyinjiao): Meeting point of three Yin meridians (Liver, Spleen, Kidney) — nourishes Blood and Yin, calms the spirit
• GV-20 (Baihui): Lifts Yang, clears the mind
• HT-7 (Shenmen): Calms the Shen, improves sleep
• KI-3 (Taixi): Source point of the Kidney meridian — tonifies Kidney Yin and Yang
• BL-18 (Ganshu) + BL-20 (Pishu) + BL-23 (Shenshu): Back-Shu points of Liver, Spleen, Kidney — tonifies all three organ systems simultaneously

Additional Points Based on Pain Location: Ashi points, corresponding meridian points along the primary pain distribution

Electroacupuncture: 2/100 Hz alternating, applied to ST-36 and LI-4 bilaterally. This maximizes endogenous opioid release through the combined mu/kappa/delta receptor activation described by Han.

Treatment Frequency: 2x/week for 8-12 weeks (16-24 sessions). Fibromyalgia requires more sustained treatment than localized pain conditions because the central sensitization has developed over months to years and requires corresponding time to reverse.

Knee Osteoarthritis

Acupuncture for knee OA has Level 1 evidence from Vickers’ meta-analyses and is recommended in multiple clinical guidelines (ACR 2019 conditionally recommends acupuncture for knee OA).

Primary Points:

• ST-35 (Dubi) + Extra Point Xiyan (Medial Eye of the Knee): These two points bracket the patellar tendon on either side of the knee, forming the classical “Eyes of the Knee” combination. Directly address local inflammation and pain.
• ST-36 (Zusanli): Below the knee — local-distal point for knee and leg
• SP-9 (Yinlingquan): Resolves Dampness in the knee joint (effusion)
• GB-34 (Yanglingquan): Influential point for tendons and ligaments
• BL-40 (Weizhong): He-Sea point of the Bladder, addresses posterior knee pain
• SP-10 (Xuehai): “Sea of Blood” — activates blood circulation in the knee

Electroacupuncture: 2 Hz or 2/100 Hz between ST-35 and Xiyan or across the most affected joint compartment. 20-30 minutes.

Adjunctive: Warm needle technique (moxa on the handle of the needle) or heat lamp directed at the knee during treatment — Kidney Yang Deficiency with Cold-Dampness is the most common underlying pattern in knee OA.

Integration with Functional Medicine Pain Management

Acupuncture addresses the nervous system component of pain. Functional medicine addresses the biochemical and structural components. Together:

1. Reduce inflammation at the source: Anti-inflammatory diet (Mediterranean, elimination of food sensitivities), omega-3 fatty acids (EPA 2-3g/day), curcumin (1-2g/day), SPMs (specialized pro-resolving mediators)
2. Address central sensitization: Acupuncture (descending inhibition, opioid release), sleep optimization (central sensitization worsens with sleep deprivation), vagal toning (see acupuncture-anxiety-depression-vagal-tone.md)
3. Repair tissue: Collagen peptides, vitamin C, hyaluronic acid, PRP/prolotherapy for structural damage
4. Modulate the immune component: Gut healing (intestinal permeability drives systemic inflammation), microbiome restoration, food sensitivity elimination
5. Address the emotional component: Chronic pain always has an emotional overlay — fear, grief, anger, helplessness. These are not “in the patient’s head” — they are in the nervous system, amplifying pain through limbic-cortical circuits. Acupuncture, particularly at points like HT-7, PC-6, GV-20, and Yintang, addresses the emotional dimension of pain directly. (See also: ../emotional-healing/)

Cross-Connections

• For the vagal anti-inflammatory pathway: see acupuncture-autoimmune-modulation.md
• For electroacupuncture neuroscience: see electroacupuncture-neuroscience-mechanisms.md
• For anxiety and emotional overlay in pain: see acupuncture-anxiety-depression-vagal-tone.md
• For moxibustion, cupping, and gua sha as adjuncts: see moxibustion-cupping-gua-sha-evidence.md
• For the meridian pathways involved: see meridian-system-bioelectric-network.md

References

• Deare, J. C., Zheng, Z., Xue, C. C., et al. (2013). Acupuncture for treating fibromyalgia. Cochrane Database of Systematic Reviews, (5), CD007070.
• Goldman, N., Chen, M., Fujita, T., et al. (2010). Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nature Neuroscience, 13(7), 883-888.
• Han, J. S. (2004). Acupuncture and endorphins. Neuroscience Letters, 361(1-3), 258-261.
• Huang, C., Wang, Y., Han, J. S., & Wan, Y. (2002). Characteristics of electroacupuncture-induced analgesia in mice: variation with strain, frequency, intensity and opioid involvement. Brain Research, 945(1), 20-25.
• Linde, K., Allais, G., Brinkhaus, B., et al. (2016). Acupuncture for the prevention of episodic migraine. Cochrane Database of Systematic Reviews, (6), CD001218.
• MacPherson, H., Vertosick, E. A., Foster, N. E., et al. (2017). The persistence of the effects of acupuncture after a course of treatment: a meta-analysis of patients with chronic pain. Journal of Pain, 18(2), 154-165.
• Mayer, D. J., Price, D. D., & Rafii, A. (1977). Antagonism of acupuncture analgesia in man by the narcotic antagonist naloxone. Brain Research, 121(2), 368-372.
• Melzack, R., & Wall, P. D. (1965). Pain mechanisms: a new theory. Science, 150(3699), 971-979.
• Napadow, V., Makris, N., Liu, J., Kettner, N. W., Kwong, K. K., & Hui, K. K. S. (2005). Effects of electroacupuncture versus manual acupuncture on the human brain as measured by fMRI. Human Brain Mapping, 24(3), 193-205.
• Qaseem, A., Wilt, T. J., McLean, R. M., & Forciea, M. A. (2017). Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians. Annals of Internal Medicine, 166(7), 514-530.
• Torres-Rosas, R., Yehia, G., Peña, G., et al. (2014). Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nature Medicine, 20(3), 291-295.
• Vickers, A. J., Cronin, A. M., Maschino, A. C., et al. (2012). Acupuncture for chronic pain: individual patient data meta-analysis. Archives of Internal Medicine, 172(19), 1444-1453.
• Vickers, A. J., Vertosick, E. A., Lewith, G., et al. (2018). Acupuncture for chronic pain: update of an individual patient data meta-analysis. Journal of Pain, 19(5), 455-474.