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MECHANISMS OF ACUPUNCTURE

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This material is supplementary to Chapter 3 (Modern Acupuncture) of my book "Acupuncture in Practice", which dealt with ideas about the mechanisms of acupuncture from a modern perspective. Since I wrote that chapter new information has come to light so this is an update. In part I am drawing on an important paper by C.Carlsson[1].

Problems with much of the research to date

Much of the research that has been carried out on the mechanisms of acupuncture probably tells us little about what happens in the clinical setting. There are several reasons for this.
  1. A lot of the work has been done on animals rather than humans.
  2. The animal research is based on short-term reductions in pain, which probably work via DNIC (diffuse noxious inhibitory control) and stress-induced analgesia, neither of which are relevant to clinical application to humans.
  3. Almost all the experimental work, whether on humans or on animals, has used electrical stimulation, but much clinical acupuncture is done using manual stimulation.
  4. Most of the human experiments that have been done show only short-term and rapid-onset pain relief, which does not predict the clinical outcome.
  5. Strong painful stimulation is needed to raise pain threshold in humans.
In summary, we need to distinguish acupuncture analgesia from therapeutic acupuncture. They probably have different mechanisms of action.

So what about the mechanisms of clinical acupuncture?

Clinically, acupuncture appears to work at a number of different levels.
  1. Local effects may be related to the release of substances in the tissues (neuropeptides and endorphins).
  2. Within the spinal cord there are various pain-regulating mechanisms including the gates in the posterior horn postulated by Melzack and Wall; there is also the phenomenon of LTP/LTD (to be discussed later).
  3. There are important descending pathways, many of which originate in the brain stem (peri-aqueductal grey, nucleus raphe magnus, and other brain stem areas) which modulate pain transmission.
  4. Cortical and psychological influences operate, including the "placebo" effect.
  5. Oxytocin is thoughT TO have a role (see below).

Oxytocin

Oxytocin is generally thought of as a hormone related to parturition and lactation, but its role is wider than this. It is a 9-amino-acid polypeptide produced by nuclei in the hypothalamus which gives rise to relaxation and pain relief in both animals and humans. This effect increases with repeated application; recall that, clinically, repeated acupuncture has the same effect.

In evolutionary terms, oxytocin is very interesting. It is structurally very similar to vasopressin, and both vasopressin and oxytocin are involved in mating behaviour in animals. Vasopressin affects the reward centres in the brain in some animals. It has been suggested, e.g. by Matt Ridley[2], that at the human level falling in love may be related to oxytocin.

There are some reports of oxytocin levels rising in response to acupuncture and also two reports of anomalous milk secretion (galactorrhoea) occurring during acupuncture. One, reported by C.Jenner and J.Filshie[3], occurred in a woman who was having acupuncture at a number of sites round the shoulder for post-mastectomy symptoms. The other, reported by J.Macglashan and me[4], described a case in which it occurred following periosteal needling of the first metatarsal and first phalanx.

Claims for the role of oxytocin release in long-term symptom relief by acupuncture therefore seem plausible.

LTP and LTD

LTP is long-term potentiation; LTD is long-term depression. Both refer to neural plasticity (changes in structure and function within the central nervous system). LTP is an important phenomenon which has been widely studied in relation to memory. Initially found to occur in the hippocampus, it is now known to be widespread throughout the central nervous system. The essential idea is that increased neural activity leads to a long-lasting increase in the excitability of neurons through structural modifications at pre-synaptic and post-synaptic sites.

Chronic pain could be thought of as a form of learning (see K.Sufka[5]). That is, in chronic pain changes occur within the spinal cord and probably the brain which increase the rate of transmission of pain information. These changes are due to LTP. If this process could be reversed (by LTD) the result would be reduced pain transmission and perception. The hypothesis is that acupuncture has such an effect.

Central brain changes in acupuncture

New techniques for observing brain function directly, such as fMRI and PET, have been applied to acupuncture and the preliminary results are interesting. They appear to show definite changes in some brain areas, such as the anterior cingulate cortex, the amygdala, and the insula, which might be expected if acupuncture reduced the unpleasantness of pain without necessarily making much difference to the perception of pain. Clinical experience suggests that this does occur in some cases.

Some people have hailed these findings as "proof" that acupuncture works. However, it is not clear that acupuncture is unique in producing effects of this kind. Very similar phenomena are seen with placebos and hypnosis. I discuss this question at more length in a recent paper[6].

The role of tactile C fibres in promoting feelings of well-being is of interest and I have discussed the implications of this for acupuncture practice and research recently[7].

Conclusions

Although we are still a long way from being able to specify in detail, the mechanisms by which acupuncture produces its effects, new techniques are shedding more light on the matter and it is becoming increasingly clear that there is a genuine physiological basis for the phenomena.

However, I think that acupuncture will turn out to be one of a number of rather similar techniques for modifying the behaviour of the central nervous system in relation to pain. There is probably a final common path for many physical treatments that focuses on the so-called limbic system. The role of acupuncture in relation to these other methods thus still remains to be clarified.

References:

  1. Carlsson C, Acupuncture mechanisms for clinically relevant long-term effects: reconsideration and a hypothesis. Acupuncture in medicine 2002(2-3);20:82-99
    Abstract: From the author’s direct involvement in clinical research, the conclusion has been drawn that clinically relevant long-term pain relieving effects of acupuncture (>6 months) can be seen in a proportion of patients with nociceptive pain. The mechanisms behind such effects are considered in this paper.

    From the existing experimental data some important conclusions can be drawn:

    1. Much of the animal research only represents short-term hypoalgesia probably induced by the mechanisms behind stress-induced analgesia (SIA) and the activation of diffuse noxious inhibitory control (DNIC).

    2. Almost all experimental acupuncture research has been performed with electro-acupuncture (EA) even though therapeutic acupuncture is mostly gentle manual acupuncture (MA).

    3. Most of the experimental human acupuncture pain threshold (PT) research shows only fast and very short-term hypoalgesia, and, importantly, PT elevation in humans does not predict the clinical outcome.

    4. The effects of acupuncture may be divided into two main components – acupuncture analgesia and therapeutic acupuncture.

    A hypothesis on the mechanisms of therapeutic acupuncture will include:

    1. Peripheral events that might improve tissue healing and give rise to local pain relief through axon reflexes, the release of neuropeptides with trophic effects, dichotomising nerve fibres and local endorphins.

    2. Spinal mechanisms, for example, gate-control, long-term depression, propriospinal inhibition and the balance between long-term depression and long-term potentiation.

    3. Supraspinal mechanisms through the descending pain inhibitory system, DNIC, the sympathetic nervous system and the HPA-axis. Is oxytocin also involved in the long-term effects? 4. Cortical, psychological, “placebo” mechanisms from counselling, reassurance and anxiety reduction.

    {Full text available on-line as PDF.)

  2. Ridley M, 2003.Nature via Nurture: 42-4

  3. Jenner C, Filshie J. Galactorrhoea following acupuncture. Acupuncture in Medicine 2002;20(2-3):107-8.

  4. Campbell A, Macglashan J. Acupuncture-induced galactorrhoea - a case report. Acupuncture in medicine 2005;23(3):146.

  5. Sufka K, Chronic pain explained. Brain and Mind, 2000;1(2):155-179

  6. Campbell A, Point specificity of acupuncture in the light of recent clinical and imaging studies. Acupuncture in medicine 2006;24(3):118-122.

    Abstract: One fundamental question that is still not resolved is whether acupuncture needles must be inserted in specific points to have their greatest effects. In the majority of large RCTs recently conducted in Germany, acupuncture was significantly more effective than doing nothing but not than sham acupuncture. Only for one study of chronic knee pain was acupuncture superior to sham.

    Brain imaging with functional magnetic resonance (fMRI) and positron emission tomography (PET) may be helpful but is still in its early stages. Several studies have shown differences between the way the deep central areas of the brain respond to genuine acupuncture compared with sham. Acupuncture can clearly produce complex changes that are relevant to pain transmission and perception, though it is still uncertain how specific these are. Similar changes have been seen after the application of placebo cream and after hypnosis.

    A previous paper discussed the likely central role of the limbic system in acupuncture, evidenced by euphoria and out of body experiences. There may be a good deal of common ground between acupuncture, placebo treatments, hypnosis, and even manipulative treatments. This understanding could offer a way out of the sterile debate about whether acupuncture is merely a placebo: acupuncture could be one effective way of stimulating responses within these deep areas of the brain, though not the only way.

    (Full text available on line as PDF.)

  7. Campbell A, Role of C tactile fibres in touch and emotion - clincal and research relevance to acupuncture. Acupuncture in medicine 2006;24(4):169-171.
    Abstract: Acupuncture is generally thought to rely on A-delta fibre stimulation for its effects and the role of C fibres has been largely discounted. Recent research, however, shows that there are C tactile fibres in humans that respond to light touch and project to the limbic system. They are thought to be responsible for feelings of calm and wellbeing that are elicited by gentle manual stimulation, as in stroking. These findings are likely to be relevant to acupuncture as regards both clinical practice and research. They may explain why even superficial acupuncture with brief needle insertion can have a clinical effect and why light touch may not be an adequate control procedure for use in clinical trials.

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