Thanks to the New Zealand Acupuncture Website for the use of this article!
Dr. Linus Soh F.A.M.A.S.
In the last 20 years much has been written about acupuncture and its
efficiency in relieving pain. The ancient Chinese clinicians practised
acupuncture based on Traditional Chinese Medicine (TCM) principles using well
established guidelines. Their reasoning were based on empirical
responses rather than scientific principles. This discussion hopes to
bring to highlight some recent research findings. Acupuncture research
however cannot stagnate as we move towards the next century in pursuit of a
better understanding of its mechanics.
Since the discovery of enkephalins from pigs' brains (by Hughes, Kosterlitz at
Aberdeen) in 1975, the scientific community has tried to explain
scientifically how acupuncture's pain relieving mechanisms really works.
When Beta-endorphin was discovered (by C.H. Li at Stanford University)
in 1976 and dynorphin (by Goldstein) in 1979 it began to become clear that
electro-acupuncture (EA) will increase the levels of B-endorphin at 2-4Hz and
dynorphin at 100-200Hz. Enkephalins will be released at frequencies of
2-200Hz. Based on the tail flick latency response in rats, Professor Han
(Beijing University) also found that naloxone will even block EA response to
high frequency stimulation. This was previously unknown as the dose of
naloxone used was 1-2mg/kg whereas Han used 10-20mg/kg. In his
experiments on rats Professor Han also used Captopril (a commonly used ACE
inhibitor in general practice). When injected into the peri-aqueductal
grey (PAG) Captopril prolongs the analgesic effects of EA as it is also an
Anti-opioid substances (AOS) were also described. These are released due to
excessive EA and are thought to account for acupuncture tolerance.
Indeed GABA and CCK8 have also been found to be increased after excessive
morphine usage. Morphine tolerance hence often equated to EA tolerance.
Whether the biochemical interaction are similar needs clarification. Recent
studies show that the two main morphine metabolites are morphine-3-glucuronide
(M3G) and morphine-6-glucuronide (M6G). M3G antagonises morphine
analgesia while M6G is an agonist.
This relationship needs to be translated to EA tolerance but much
research needs to be done. It may also help us understand the
difficulty in treating patients addicted to opiates with EA.
At the last IASP conference in 1993, researchers have mentioned the discovery
of morphine within the human body. This endogenous morphine (not
endorphins) was found in patients who were taking L-Dopa for Parkinson's
disease. As these patients were not on morphine medication the plasma
levels of morphine must have been produced by the body itself.
However, so far no details are known of the exact pathways involved.
Perhaps in the future EA responses may have to be interpreted in a different
manner in the light of this new knowledge.
The 1993 IASP Conference in Paris also produced evidence of a new pain
pathway. The French team described this new pathway, called the
spino-ponto-amygdaloid pathway. Noxious stimuli have been shown to
project to the lateral parabrachial (PB) nucleus at the pontine level, and
then directly to the central nucleus of the amygdala. Morphine needed
to depress the noxious signals in the PB and amygdala are lower than that
required at the spinal levels. This new pathway which have been
implicated in the affective emotional aspects of pain. It seems to be
highly sensitive to morphine. The amygdala has also been researched by
Professor Han and has been found to involve serotonin and endorphins.
When tested with cinanserin (a serotonin receptor blocker) and naloxone, EA
analgesia was attenuated. This nucleus seem to play a big role in
facilitating EA responses for pain relief. The discovery of this new
pain pathway should add impetus for more research.
Serotonin (5HT) receptors sites have also been the subject of intense
scrutiny over the last few years. There are now many subtypes of 5HT
receptors namely 5HT, 5HT2, 5HT3, 5HT4 etc. 5HT1 is further subdivided
into 5HT1A, 5HT1B, 5HT1C, 5HT1D. Research into the latter has given us
sumatriptan which is a currently clinically used for migraine. The
effect of EA on release of monoamines (down the descending inhibitory pathway)
is well documented. Research using cinanserin (a 5HT receptor
antagonist) and parachlorophenylalanine (PCPA - a 5HT synthesis antagonist)
have shown EA to be decreased markedly. Conversely, Tryptophan (the
precursor of 5HT) would enhance EA. However the many subtypes of 5HT
receptors add a new challenge to acupuncture research. It is
interesting to speculate if different frequencies will stimulate different 5HT
receptors. If this is more clearly understood perhaps TCM may one day
be explained along scientific paradigms.
Research into naloxone have shown that ultra-low doses (in nanograms) can
have an analgesic effect. This seemingly paradoxical effect have
mystified and at the same time excited scientists around the world.
Various experiments performed in rat models of clinically induced arthritic
pain have shown that extremely low doses of naloxone can have a paradoxical
analgesic effect, while high doses induce hyperalgesia. It must be
remembered that we often use naloxone for reversal of opiate toxicity.
Recent research into spinal receptor systems have revealed an important
receptor which is currently the centre of great scientific interest.
The NMDA (N-methyl-D-Aspartate) receptor reflects Aspartate and Glutamate
activity in nociception. Ketamine (a NMDA antagonist) has been shown to
produce analgesia when introduced to the dorsal horn. Glutamate and
GABA seem to have opposing effects on neuronal cells. GABA anti-sera
has been used to reverse acupuncture and morphine tolerance as well as
non-responders to EA. Quite clearly the NMDA receptor should be more
thoroughly researched in relation to acupuncture induced analgesia.
It can be seen from the above discussion we may have to rethink how
acupuncture works. More and more research have enabled us to understand the
complexities of nociceptive afferent stimulation of the dorsal horn,
especially laminae I & II. It is to be hoped that acupuncture
researchers will keep up with the new knowledge and perhaps unravel the
mechanics of how acupuncture works in pain relief.
Pharmacological Approaches to the Treatment of Chronic Pain: New Concepts
and Critical Issues - Progress in Pain Research and Management Volume 1.
IASP Press 1994
Editors - H.L. Fields, J.C. Liebeskind
Proceedings of the 7th World Congress on Pain - Progress in Pain Research
and Management Volume 2.
IASP Press 1994
Editors - G.F. Gebhart,D.L. Hammond & T.S. Jensen
The Neurochemical Basis of Pain Relief by Acupuncture
Professor J.S. Han - 1987.