Acupuncture is a potentially cheap and safe form of treatment for relieving some types of pain, yet many doctors in the West remain sceptical of its value. They find the ancient Chinese concepts of traditional acupuncture and its claim to be a treat ment for all ills unacceptable, but these concepts may be largely irrelevant to the practice of effective analgesic acu puncture. Sceptics suggest that acupuncture may be nothing more than a powerful placebo. If, however, acupuncture exerts some specific analgesic effect like other physical treatments, this is not amenable to proof by formal clinical trial. Acu puncture may be performed in several ways, including manual rotation of the needles and low-frequency or high-frequency electrical stimulation .through them. No truly double-blind comparison can be made with alternative treatments since the needles must be inserted in the conscious patient. Despite the scepticism, however, evidence is accumulating about its mechanisms of action.

The possibility that acupuncture analgesia is mediated by a humoral factor was first suggested by a report that transfer of cerebrospinal fluid from rabbits having acupuncture produces analgesia in recipient rabbits.1 The time course of analgesia is similar whether induced by acupuncture or by stimulation of the brainstem periaqueductal grey matter, both forms of stimulation producing effects with a delayed beginning and end.2 Analgesia induced by stimulating neurones of the periaqueductal grey matter appears to be mediated by endo genous opiate-like peptides,3 so perhaps analgesia after acupuncture is produced by the release of similar endogenous substances.

The endogenous peptides with opiate-like analgesic effects are broadly classed as enkephalins and endorphins. Research into the role of these opioids in acupuncture analgesia falls into into two main categories: firstly, the use of drugs modifying opiate action and, secondly, the measurement of opioid peptide concentrations in blood and cerebrospinal fluid. The specific opiate-receptor-blocking drug naloxone reduces or abolishes low-frequency (2-6 Hz) electroacupuncture analgesia in various animals subjected to pain.4-7 Naloxone has no effect, however, on the analgesia induced by high-frequency (200 Hz) electroacupuncture in mice.4 The degree of analgesia in these studies was assessed by behavioural measurements,4-5 by the depression of the firing rate of pain-transmitting (nociceptive) spinal neurones,6 or by changes in pain-induced cortical evoked potentials.7 In human subjects with chronic or experi mental pain all but one group of workers report that naloxone reduces the analgesia produced by manual acupuncture or low-frequency electroacupuncture via needles or surface electrodes.28-10

Certain D-amino-acids inhibit the peptidases that otherwise rapidly degrade the endorphins, thus limiting the duration of their effects. These D-amino-acids enhance the effect of low-frequency electroacupuncture in mice, the resulting analgesia being reversible by naloxone.11 Mice of the inbred strain CXBK have a low density of opiate receptors in the brain and achieve little analgesia after morphine or acupuncture.12 In contrast, the related group of C57BL mice, which have a normal density of brain opiate receptors, respond to acu­puncture and morphine with normal analgesia. This evidence further supports a role for endogenous opioid peptides in acupuncture analgesia.

Some recent evidence points to the release of opioid pep­tides in cerebrospinal fluid during acupuncture analgesia. Several workers have shown an increase in opiate-like activity in the cerebrospinal fluid of animals and man during acu­puncture, 13 but this was measured by a radioreccptor assay that lacked specificity and did not identify structurally discrete peptides. Clement-Jones et al16 18 measured cerebrospinal concentrations of beta-endorphin and met-enkephalin by radioimmunoassay in two groups of patients before and after 30 minutes of electroacupuncture. They used a highly specific met-enkephalin assay that had insignificant cross-reaction with other peptides.16 A group of patients with recur­rent pain received low-frequency electroacupuncture. Concen­trations of met-enkephalin in the cerebrospinal fluid were unchanged but those of beta-endorphin rose after electro-acupuncture.17 In a second study, in heroin addicts who were being withdrawn from their drugs, high-frequency electro-acupuncture was given to suppress the symptoms and signs of withdrawal. Clinically the treatment was highly effective and it was associated with a rise in met-enkephalin concentrations, which had been low before treatment; beta-endorphin concentrations, which were raised initially, did not change after electroacupuncture.18 The difference between the effects on beta-endorphin and met-enkephalin may be due to the different conditions being treated, but more probably relate simply to the frequencies of the stimuli. Thus low-frequency electroacupuncture releases beta-endorphin, whose effects can be blocked, at least in part, by naloxone; whereas high-frequency electroacupuncture may release met-enkephalin, whose effects are not blocked by conventional doses of nal­oxone.

Information about changes in opioids in blood during acu­puncture is more confused. The results of two studies suggest that circulating immunoreactive beta-endorphin rises during electroacupuncture,19-20 but stress was not excluded as a cause of the changes. Beta-endorphin is released from the pituitary in parallel with adrenocorticotrophic hormone and the lipo-trophins during stress and indeed all other known stimuli. Other workers have reported a fall in plasma adrenocortico­trophic hormone as well as beta-endorphin and cortisol concentrations during electroacupuncture,18-21 an effect com­patible with the central release of enkephalins.22-23 In any event, beta-endorphin released into the blood is unlikely 10 mediate the central analgesia induced by acupuncture, since this peptide penetrates poorly into the central nervous system. Pomeranz et al found that hypophysectomy blunted the analgesic response to low-frequency electroacupuncture,24 but this has not been confirmed. In man the pituitary is probably not an important source of cerebral beta-endorphin, since the concentrations in the cerebrospinal fluid are normal in patients with panhypopituitarism, who have undetectable plasma concentrations of beta-endorphin.25

5-Hydroxytryptamine (serotonin) probably plays an important part in mediating the analgesic effect of acu­puncture.26-28 The tryptophan hydroxylase inhibitor para-chlorphenylalanine decreases concentrations in the brain of 5-hydroxytryptamine but works in the opposite way to naloxone, reducing the analgesic effect of high-frequency electroacupuncture in mice but having no effect on low-frequency electroacupuncture analgesia.4 Other neurotrans-mitter systems may mediate some effects of acupuncture but so far their role is uncertain.28-29

The effects of low-frequency electroacupuncture and manual acupuncture may be mediated, at least in part, by stimulation of beta-endorphin-containing neurones of the peri-aqueductal grey matter, thereby activating endogenous pain-control pathways. An important 5-hydroxytryptamine-contain-ing pathway that inhibits pain arises in the nucleus raphe magnus in the medulla and projects to the spinal dorsal horns. Stimulation of this serotoninergic system activates inhibitory enkephalinergic interneurones situated in the spinal dorsal horns, which in turn inhibit the activity of nociceptive neurones in the dorsal horns.30 Possibly high-frequency electroacupuncture has an effect in activating this serotonin-ergic-enkephalinergic system.

Can we now assert that acupuncture is more than a placebo ? This question seems no longer relevant, since the relief of pain associated with placebos is probably also mediated by release of endogenous opioids and can be blocked by naloxone.31 Perhaps the evidence that different forms of acupuncture elicit specific neurohumoral effects to produce analgesia in animals and man gives acupuncture some physiological respectability. In any event, if acupuncture provides effective and safe pain relief then its mechanism of action is of secondary importance. The most fruitful result of research into the neurochemical basis of acupuncture may be the discovery of a means of increasing cerebral release of specific opiate-like peptides and other neurotransmitters. This may be useful for investigating and treating pain and perhaps also some neuro­logical, psychiatric, and neuroendocrine diseases.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1506864/?page=1

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1506864/pdf/bmjcred00677-0006.pdf

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