++
Over the last 30 years, a great deal of scientific evidence has
accumulated to verify that both acupuncture stimulation (AP) and
electro-acupuncture stimulation (EA) has reproducible physiologic effects.
There are three main lines of evidence that are presented in the
following discussion. All go to the heart of the neurologic mechanisms
that are currently understood to modulate and influence pain.
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The evidence for the release of endogenous opioids with AP and
EA derives from the seminal work done by Pomeranz3 in
animals and Mayer4 in humans in the 1970s. Since
that time, a large body of evidence has developed to show that both AP
and EA lead to the release of endorphins and enkephalins into the
cerebrospinal fluid (CSF). Furthermore, the release of these neuropeptides
have been demonstrated to play a role in the analgesic effect of
acupuncture as evidenced by opioid-receptor antagonism that can
abolish the analgesia obtained with acupuncture in both human and
animal models of acute pain.
++
Since the initial studies, both the met-enkephalin–responding
neurons in the dorsal column of the spinal cord and the endorphin
and enkephalin active sites in the periaquaductal gray zone of the brain
have been shown to be involved in acupuncture analgesia. Both the
parameters of stimulation (i.e., the intensity and frequency of
EA) and the site of stimulation have significant effects on the
type of chemical releases. In particular, antiserum to met-enkephalin
abolished acupuncture analgesia but antiserum to dynorphin did not
when a true acupuncture point was stimulated, whereas the reverse
was true when a non-acupuncture or sham point was stimulated.5
++
Electro-acupuncture stimulation has also been found to elevate
levels of 5-hydroxytryptamine (5-HT) in the raphe nucleus, which
enhances acupuncture analgesia presumably through descending inhibitory
control mechanisms. Destruction of these neurons in the raphe nucleus
of the mid-brain or injection of paracholorophenylalanine, which
lowers cerebral levels of 5-HT, will attenuate acupuncture analgesia
and injection of pargyline, which slows enzymatic degradation of
5-HT, enhances acupuncture analgesia.6
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The hypothalamic–pituitary–axis and catecholamines
are also influenced by EA and AP and may further influence the analgesic
response to pain both through immune modulation and modulation of
the sympathetic responses.
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Recent technological advances in mapping brain activity using
functional magnetic resonance scanning (fMRI) have begun to be applied
to acupuncture. Comparison has been made between tactile sensation
(tapping the skin with a wire at 2Hz) versus AP using a manual stimulation
technique. The acupuncture stimulation used in this study involved
twisting the needle at 2Hz in LI4 (a point in the first dorsal interosseous
muscle of the hand). Stimulation of an acupuncture point in this
manner produces a deqi sensation, which is a full, aching feeling
at the point of the needle and is believed to be important in obtaining
the clinical effect with AP. The results of unilateral AP showed
bilateral neural modulation of cortical and subcortical structures.
The primary action was to decrease signal intensity in the limbic
region and other subcortical areas. Tactile stimulation did not
produce these changes in fMRI. In addition, if the needle was placed
in the point and left at rest, or placed just subcutaneously and
not in the muscle, fMRI signal decrease in these deep subcortical
structures was not seen. This suggests that the response of the
organism to AP depends on activation of the muscle sensory afferents
and not the superficial afferents in the skin.7
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Evidence for point specificity has also been obtained in a recent
study by Cho et al.8 An acupuncture point on the
lateral aspect of the small toe, Bladder 67 (B67), which is known
as an influential point for vision, was stimulated and observed
to cause increased fMRI activity in the occipital lobes in 12 subjects.
Stimulation of the eyes directly with light caused a similar activation,
whereas stimulation of a sham acupuncture point 2 to 5 cm away from
B67 failed to cause occipital lobe activation.
++
Both of these studies are preliminary, however; they suggest
that the grid of acupuncture points that has evolved over the last
2000 years may indeed represent a network of nodes in the peripheral
nervous system that have profound and specific effects on modulating
and regulating the activity of the central nervous system.
++
It is still an open question whether acupuncture has an influence
on pain and other disease states that goes beyond the direct effect
of the chemical releases previously mentioned. The early data using
fMRI suggest that the sensory stimulation provided by acupuncture
may have direct and selective effects on CNS function. Although
the demonstration that endogenous opioids can be consistently released
in both animal and human experimental models has been an important
step in verifying that acupuncture analgesia has a physiologic basis,
there continues to be debate about whether this effect is sufficient
to explain the observed clinical benefits. One of the problems is that
such humoral effects are nonspecific and short-lived and cannot
explain why certain treatment methods for particular conditions
would have a sustained or permanent disease-modifying result. The
chemical releases observed with EA and AP may just be an epiphenomenon,
indicating that there is an influence on the CNS without yet comprehending
what the actual changes are. Table 78-1 lists the problems with
our current understanding of acupuncture analgesia.
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To give just one example of how the neurohumoral model fails
to fully comprehend the clinical effect of AP, there is a recently
published study using heat stimulation (moxabustion) of an acupuncture
point on the fifth toe (B67) to turn breech babies after the 33rd
week of pregnancy. The results of the study were profound, showing
a significantly improved turning of the infants to the cephalic
position at delivery compared with the control group. Of 130 fetuses
in the intervention group, 98 (75.4%) were cephalic, compared
with 62 (47.7%) of 130 fetuses in the control group (P < .001;
relative risk = 1.58; 95% CI,
1.29–1.94).9
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One theory that may help to better explain the long-term effect
of EA and AP is that by stimulating peripheral sensory afferents
of the skin and muscle, sustained changes occur in the CNS through
central neuromodulation. We are now just beginning to understand
the basic mechanisms of pathologic neuromodulation that can lead
to chronic pain. A fundamental concept that has emerged is that
sustained nociceptive input can have profound effects on the CNS
that cause adverse neuroplastic changes.10 Interestingly,
continuing along this line of argument, unlike transcutaneous electrical
nerve stimulation (TENS), AP and EA do rely on a more “painful
stimulation” of the peripheral nervous system.11 In
effect then, through controlled stimulation of peripheral nociceptors,
acupuncture may be causing a reverse neuroplasticity in the CNS.
++
A clue to the neuroplastic changes that may be occurring in the
CNS with EP and AP can be found in the literature looking at c-fos
expression. The production of the fos protein in spinal cord and
cerebral neurons is known to occur with painful peripheral nerve
stimulation and can act as a guide to the location of neurons that
have been activated by this noxious input. It is believed that the
observed c-fos release in the CNS couples transient intracellular
signals to long-term changes in the central processing of peripheral
sensory input and heralds the initiation of adverse neuroplastic
changes in response to nociceptive input.12
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We now know that EP causes the expression of c-fos in certain
cells of the CNS, but in cells that are different than those that
express c-fos with noxious input.13 In addition,
EA has been shown to suppress fos expression in the spinal cord
dorsal horn in response to mechanical noxious stimulation.14 This
early data with animal models suggest that some form of reverse
neuroplasticity is taking place with acupuncture stimulation.
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Another approach to studying the neuromodulatory effect of peripheral
nerve stimulation with acupuncture on the CNS utilizes somatosensory-evoked
potentials (SEP). The most fruitful of this method is the pain SEP,
which is the evoked potential generated when recording over the
skull with painful stimulation in the periphery. Dental pulp stimulation
is the most reliable model for this technique. In a recent review,
Xu presents strong arguments to suggest that AP and EA have a suppressive
effect on pain SEPs and that this effect is point-specific, in that
stimulation of points on unrelated meridians fail to provide a suppressive
effect on the pain SEP. This argues against a purely neurohumoral
acupuncture effect since one would expect that if suppression of
the pain SEP depended only on the release of endogenous neuropeptides
then any point would do, and that meridian-specific points would
not be superior in efficacy.15