Scientific theories regarding acupuncture

Scientific studies have been conducted concerning the hypothesized principles underlying the proposed mechanism of action of acupuncture.

Nerve-reflex theory

The nerve-reflex theory (developed by Ishikawa and Fujita et al. in the 1950s) proposed the reflex interactions between the periphery and the autonomic nervous system. This theory states that the skin (cutaneous) surface and internal organs (visceras) are intimately connected by these reflexes — "viscera-cutaneous reflex" and "cutaneous-viscera reflex."

These reflexes can be related to the neuroendocrine-autonomic responses, which is mediated partly by the hypothalamic-pituitary-adrenal axis (HPA axis). HPA axis is a complex set of feedback interactions between the hypothalamus (located in the midbrain), the pituitary (located beneath the brain) and the adrenal glands (located in the kidneys). The HPA axis is a major part of the neuroendocrine system that regulates stress responses and maintains the homeostatic condition of autonomic responses directly or indirectly, such as circulation regulation, breathing regulation, feeding behavior, weight control and digestion, immune responses, pain responses, acute stresses and chronic stresses, mood states, sexual/reproductive responses, growth, fluid balance and metabolic energy balances.

In 2006, a broad sense hypothalamus-pituitary-adrenal (BS-HPA axis) model was proposed to explain the hypothesized analgesic effect of acupuncture based on observed neuroimaging (brain scanning) results using fMRI (functional resonance magnetic imaging) technique. [Cho ZH, Hwang SC, Wong EK, Son YD, Kang CK, Park TS, Bai SJ, Kim YB, Lee YB, Sung KK, Lee BH, Shepp LA, Min KT. Neural substrates, experimental evidences and functional hypothesis of acupuncture mechanisms. Acta Neurol Scand. 2006;113:370-7.] The model incorporated the stress-induced HPA axis model together with neuro-immune interaction including the cholinergic anti-inflammatory model.

Gate-control theory of pain

The "gate control theory of pain" (developed by Ronald Melzack and Patrick Wall in 1962 [P.D. Wall, R. Melzack, On nature of cutaneous sensory mechanisms, Brain, 85:331, 1962.] and in 1965 [R. Melzack, P.D. Wall, Pain mechanisms: A new theory, Science, 150:171-9, 1965.] ) proposed that pain perception is not simply a direct result of activating pain fibers, but modulated by interplay between excitation and inhibition of the pain pathways. According to the theory, the "gating of pain" is controlled by the inhibitory action on the pain pathways. That is, the perception of pain can be altered (gated on or off) by a number of means physiologically, psychologically and pharmacologically. The gate-control theory was developed in neuroscience independent of acupuncture, which later was proposed as a mechanism to account for the hypothesized analgesic action of acupuncture in the brainstem reticular formation by a German neuroscientist in 1976. [Melzack R. Acupuncture and pain mechanisms Anaesthesist. 1976;25:204-7.]

This leads to the theory of central control of pain gating, i.e., pain blockade at the brain (i.e., central to the brain rather than at the spinal cord or periphery) via the release of endogenous opioid (natural pain killers in the brain) neurohormones, such as endorphins and enkephalins (naturally occurring morphines).

Neurohormonal theory

Pain transmission can also be modulated at many other levels in the brain along the pain pathways, including the periaqueductal gray, thalamus, and the feedback pathways from the cortex back to the thalamus. Pain blockade at these brain locations are often mediated by neurohormones, especially those that bind to the opioid receptors (pain-blockade site).

Analgesic (pain-killing) action of acupuncture was demonstrated to be mediated by stimulating the release of natural endorphins in the brain. This effect can be inferred scientifically by blocking the action of endorphins (or morphine) using a drug called naloxone. When naloxone is administered to the patient, the analgesic effects of morphine can be reversed, causing the patient to feel pain again. When naloxone is administered to an acupunctured patient, the analgesic effect of acupuncture can also be reversed, leaving the patient with intense pain again. This demonstrates that the site of action of acupuncture is mediated through the natural release of endorphins by the brain, which can be reversed by naloxone. [Pomeranz B, Chiu D. Naloxone blocks acupuncture analgesia and causes hyperalgesia: endorphin is implicated. Life Sci 1976;19:1757-1762.] [Mayer DJ, Price DD, Raffii A. Antagonism of acupuncture analgesia in man by the narcotic antagonist naloxone. Brain Res 1977;121:368-72.] [Eriksson SV, Lundeberg T, Lundeberg S. Interaction of diazepam and naloxone on acupuncture induced pain relief. Am J Chin Med. 1991;19:1-7.] [Bishop B.Pain: its physiology and rationale for management. Part III. Consequences of current concepts of pain mechanisms related to pain management. Phys Ther. 1980, 60:24-37.] Such analgesic effect can also be shown to last more than an hour after acupuncture stimulation by recording the neural activity directly in the thalamus (pain processing site) of the monkey's brain. [Sandrew BB, Yang RC Jr, Wang SC. Electro-acupuncture analgesia in monkeys: a behavioral and neurophysiological assessment. Arch Int Pharmacodyn Ther. 1978 231:274-84.] It should be noted, however, that studies using similar methodological procedures, including the administration of naloxone, have suggested a role of endogenous opioids in the placebo response, demonstrating that this response is not unique to acupuncture. [cite journal |author=Amanzio, M., Pollo, A., Maggi, G., Benedetti, F. |title=Response Variability to Analgesics: a Role for Non-specific Activation of Endogenous Opioids |journal= Pain |volume=90 |issue=3 |pages=205–215 |year=2001 |pmid= |doi=] There is also a large overlap between the nervous system and acupuncture trigger points (points of maximum tenderness in myofascial pain syndrome [Melzack R, Stillwell DM, Fox EJ. Trigger points and acupuncture points for pain: correlations and implications. Pain 1977;3:3-23.] ).

Research has also suggested that the sites of action of analgesia associated with acupuncture administration are mediated through the thalamus using fMRI (functional magnetic resonance imaging) [Li K, Shan B, Xu J, Liu H, Wang W, Zhi L, Li K, Yan B, Tang X. Changes in FMRI in the human brain related to different durations of manual acupuncture needling. J Altern Complement Med. 2006;12:615-23.] and positron emission tomography (PET) [Pariente J, White P, Frackowiak RS, Lewith G. Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture. Neuroimage. 2005;25:1161-7.] brain imaging techniques, [Shen J. Research on the neurophysiological mechanisms of acupuncture: review of selected studies and methodological issues. J Altern Complement Med. 2001;7 Suppl 1:S121-7.] and via the feedback pathway from the cerebral cortex using electrophysiological recording of the nerve impulses of neurons directly in the cortex, which shows inhibitory action when acupuncture stimulus was applied. [Liu JL, Han XW, Su SN. The role of frontal neurons in pain and acupuncture analgesia. Sci China B. 1990 33:938-45.] Similar effects have been observed in association with the placebo response. One study using fMRI found that placebo analgesia was associated with decreased activity in the thalamus, insula and anterior cingulate cortex [cite journal |author=Wagner, T.D., Rilling, J.K., Smith, E.E., Sokolik, A., Casey, K.L. et al. |title=Placebo-Induced Changes in fMRI in the Anticipation and Experience of Pain |journal=Science |volume=303 |issue=5661 |pages=1162–1167. |year=2007|pmid= |doi=] .

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