West, many biomedical researchers – and, more importantly,
many physicians – question whether acupuncture merely stimulates
so-called nonspecific or placebo effects in the body. Non-specific
effects, a.k.a. subject-expectancy effects, a.k.a. placebo effects,
occur when a patient's symptoms are altered in some way (either
alleviated or exacerbated) by an otherwise inert treatment due to the
individual expecting or believing that the treatment will work. Some
people consider this to be a remarkable aspect of human physiology.1
Others consider the effect to be an illusion arising from the way medical
experiments are conducted. For instance, the entry for "acupuncture"
in the online encyclopedia Wikipedia has this to say in its second
Whether acupuncture is efficacious
or a placebo has been the subject of ongoing scientific research.
Scientists have conducted
existing clinical trials according to the protocols of evidence-based
medicine; some have found efficacy for headache, low back pain,
and nausea, but for most conditions have concluded that there is
evidence to determine whether or not acupuncture is effective.2
much of that opinion is based on equivocal human research, where
nonspecific or placebo effects cannot easily be eliminated from
the study design. On the other hand, in China, a relatively large
amount of research on acupuncture is carried out on animal models.
two advantages. First, it eliminates most, if not all, the issues
surrounding nonspecific effects, and secondly, it allows researchers
to study changes
in biochemical markers and tissues that would not be possible in
living human beings. Therefore, in my column this month, I would like
a review of some recently published studies on acupuncture in animal
models. I think this research makes it more difficult to maintain
that acupuncture simply works via nonspecific effects or placebo.
1. Zheng Ling, et al. The
influence of acupoint application & moxibustion
pretreatment on serum IL-6, testosterone, growth hormone, and cortisol
levels in rats with adjuvant arthritis in the early & secondary
stages. Zhen Ci Yan Jiu (Acupuncture Research). 2006; 6: 330-332.
The objective of this study was to observe
the effects of acupoint application and moxibustion pretreatment
on serum inflammatory cytokines
and hormones in rats with adjuvant arthritis in the early and secondary
stages. To this end, 40 Wistar rats were randomly divided into normal,
early-stage model, secondary-stage model, early-stage pretreatment,
and secondary-stage pretreatment groups. An arthritis model was created
by injecting Freund's complete adjuvant (FCA, 0.1ml) into the
rats' hind paws. After removing the hair and before injecting
FCA, respectively, a plaster made from Yin Yang Huo (Herba Epimedii)
and other Chinese medicinals was applied at acupoint Da Zhui (GV 14).
Then moxa cones were placed on top of this plaster and burned. This
was done once every other day for a total of eight times. Rats in the
four early-stage and secondary-stage groups were sacrificed on the
third and 16th days after injection of FCA, respectively. In addition,
those rats in the normal control group were also sacrificed in order
to collect blood samples. The contents of serum IL-6, testosterone
(T), growth hormone (GT), and cortisol (CORT) were assayed, respectively,
with radioimmunoassay according to the instructions in the reagent
kits. In terms of outcomes, compared with the normal group, the contents
of serum IL-6, GH, and CORT in the early-stage model and secondary-stage
model groups increased significantly (P > 0.01), and those in the early-stage
pretreatment, while serum T and GH in the early-stage and secondary-stage
pretreatment groups also increased remarkably (P > 0.05, 0.01).
However, the T level in the early-stage model group decreased significantly
(P < 0.05) in comparison to the corresponding model groups, while
the T level in the early-stage and secondary-stage pretreatment groups
increased significantly (P > 0.05, 0.01) at the same time as serum
IL-6 and GH decreased markedly (P < 0.05). Thus, the study concluded
that preconditioning of acupoints by medicinal application and moxibustion
at Da Zhui (GV 14) can effectively suppress arthritis-induced increases
in serum IL-6 and GH and decrease T to modulate inflammatory cytokines
and hormones in adjuvant arthritis rats.
2. Sheng You-xiang, et
al.The effects of electroacupuncture on deltoid opioid receptor mRNA
expression in the local focus tissues of arthritis
rats. Zhen Ci Yan Jiu (Acupuncture
Research). 2006; 6: 333-336.
The objective of this study was to observe
the effects of electroacupuncture (EA) on deltoid opioid receptor
gene expression in inflammatory tissue
in adjuvant arthritis rats in order to study the underlying peripheral
mechanism of EA analgesia. Therefore, 32 SD rats were randomized into
control, model, EA (model + EA), and normal + EA (normal animal) groups
with eight animals per group. Electroacupuncture was then applied at
2-4 V, 20-100 Hz to Xuan Zhong (GB 39) and Kun Lun (Bl 60) for 20 minutes
once per day for six days. Arthritis model was induced by injecting
Freund's complete adjuvant (FCA, 0.1 ml) in the rat's hind
paw. The latency of radiant-heat irradiation-induced leg withdrawal
was considered the pain threshold. At the end of the experiment, the
rats were anesthetized with 3% phenobarbitol (30 mg/kg) and then transcardiacally
perfused with 4% paraformaldehyde and 0.1% diethylpyrocarbonate. This
was then followed by taking a sample of the focal tissue. After routine
treatment, the tissue samples were embedded in paraffin, cut into sections,
and processed with in situ hybridization histochemistry for the observance
of delta opioid receptor mRNA. Analysis of these results showed that,
compared with the control group, the pain threshold of the model group
declined significantly (P < 0.01), while comparison between the
EA and model groups and between normal + EA and model groups showed
that the pain threshold of the two EA groups was significantly higher
(P > 0.01). Similarly, the pain threshold of the normal + EA group
was also significantly higher than that of the EA group (P > 0.01),
but no significant difference was found between the control and EA
groups in pain threshold (P < 0.05). This indicated that EA can
raise the pain threshold in both arthritis and normal rats. Secondly,
compared with the model group, the number of delta opioid receptor
mRNA expression-positive cells in the EA group was remarkably higher
(P > 0.01), thus showing marked up-regulation of delta opioid receptor
mRNA expression in the focal tissue after EA. Hence, it was concluded
that EA has a definite analgesic effect in arthritis rats that may
be related to its effect of up-regulating the expression of delta opioid
receptor mRNA expression.
3. Zhong Shu-bo, et al.
The positive effect of electroacupuncture on mitochondrial function
in rats with temporal cerebral ischemia. Zhen
Ci Yan Jiu (Acupuncture Research). 2006; 6: 337-341.
The objective of this study was to explore the protective effect of
electroacupuncture (EA) on the activity of cerebral cytochrome C oxidase
and mitochondrial DNA
(MtDNA) in cerebral ischemia-reperfusion rats (CI/R). In this study, 48 male
SD rats were evenly randomized into sham-operation, sham-operation + EA, model,
and model + EA groups with 12 animals in each group. The CI/R model was induced
by middle cerebral artery occlusion (MCAO) under anesthesia (7% chloral hydrate,
1 ml/200 g). Electroacupuncture at 1-4 mA and 5-20 Hz with dense-dispersed
waves was applied to Shui Gou (Gv 26) and Bai Hui (GV 20) for 30 minutes at
first. Stimulation was suspended for 15 minutes and then reapplied for another
30 minutes. The rats in each group were sacrificed, and their right brain hemisphere
was removed. Then the cerebral mitochondria were isolated by differential dentrifugation.
Mitochondria suspension (1 mg/ml protein) were frozen and thawed three times
at a temperature of -20°C. The activity of complex IV (cytochrome C oxidase)
was estimated by spectrophotometry and calculated. MtDNA was isolated and purified
according to the instruction in the DNA isolation kit. The concentration of
MtDNA was determined by spectrophotometry. DNA damage levels were measured
by agarose gel electrophoresis. Based on all this, it was found that, compared
to the sham-operation and sham-operation + EA groups, the activity of cytochrome
C oxidase was significantly lower in the model group (P < 0.01), while compared
to the model group, the activity of this enzyme in the model + EA group was
markedly higher (P > 0.01), thus indicating an increase in the activity
of cytochrome C oxidase after EA. There was no significant difference between
the shame and sham + EA groups in the activity of this oxidase. MtDNA in the
core of the brain focus and penumbra region were both damaged seriously. Although,
the extent of DNA damage in the penumbra region was reduced after EA treatment,
it was not reduced in the core region. Therefore, it was concluded that EA
can reduce the injury to mitochondrial function in MCAO rats. Further, this
reduction may be due to EA's effect of reducing oxidative stress of the
affected brain cells.
4. Yi Shou-xiang, et al.
The effects of moxibustion on the proliferation & apoptosis
of gastric mucosal cells and their relationship with heat shock protein
expression in stress gastric ulcer rats. Zhen
Ci Yan Jiu (Acupuncture
Research). 2006; 5: 259-263.
The purpose of this study was to observe
the effects of moxibustion at Zu San Li (St 36) and Liang Men (St
21) on the proliferation and
apoptosis of gastric mucosal cells and the relationship between the
effect of moxibustion and the expression of heat shock protein 70 (HSP70)
mRNA so as to explore the underlying molecular and biological mechanism
of moxibustion in accelerating the repair of injured gastric mucosa.
Therefore, 60 SD rats were randomly assigned to control, model, acupoint
moxibustion, and non-acupoint moxibustion groups, with 15 animals in
each group. A gastric ulcer model was established by fasting for 24
hours followed by forced water immersion at 20°C for ten hours.
Moxibustion was applied unilaterally to Zu San Li (St 36) and Liang
Men (St 21) or at a non-acupoint approximately one centimeter lateral
to each of these two points for approximately 30 minutes or four cones.
This was done once per day for eight successive days. At the end of
the experiment, the rats' gastric mucosa was sampled in order
to examine the gastromucosal injury index (ulcer index, UI, via GUTH's
method), apoptosis index (via apoptosis reagent kit), proliferating
cell nuclear antigen (PCNA, via immunohistochemical method) activity,
transforming growth factor alpha (TGF-alpha) content (via radioimmunoassay),
and HSP70 mRNA expression (reverse transcriptase-polymerase chain reaction,
RT-PCR) separately. These analyses found that, compared with the control
group, gastric mucosa UI, apoptosis index, and HSP70 mRNA expression
of the model group increased significantly (P > 0.01, 0.05),
while TGF-alpha content and PCNA numerical density decreased markedly
(P < 0.01,
0.05). In comparison with the model group, UI and apoptosis index of
the acupoint moxibustion group decreased significantly (P < 0.01,
0.05), and the TGF-alpha level, PCNA numerical density, and HSP70 mRNA
expression of the acupoint moxibustion group increased markedly (P
> 0.01). No significant differences were found between the model and
moxibustion groups in terms of UI, TGF-alpha levels, and apoptosis
index, or between the acupoint and non-acupoint groups in terms of
PCNA numerical density (P < 0.05). Thus, it was concluded that moxibustion
at Zu San Li (St 36) and Liang Men (St 21) has a protective effect
on the gastric mucosa in stress gastric ulcer rats that is closely
related to its action of promoting the synthesis of TGF-alpha and the
proliferation of the gastromucosal cells, suppressing gastromucosal
apoptosis, and up-regulating HSP70 mRNA expression.
5. Wu Zi-jian, et al. The
effects of electroacupuncture on the signal transduction of G-protein
in rat ischemic myocardial cells. Zhen
Ci Yan Jiu (Acupuncture Research). 2006; 5: 264-267.
The objective of this study was to analyze
the effects of electroacupuncture (EA) on myocardial cellular signal
transduction of G-protein in myocardial
ischemia (MI) rats in order to explore the molecular pathways of EA
against MI injury. Therefore, 20 male SD rats were randomized into
normal, model, EA-normal, and EA-model groups, with five rats in each
group. An MI model was established by occlusion of the descending anterior
branch of the left coronary artery under anesthesia to 10% chloral
hydrate (0.36 ml/100 g). Electroacupuncture at 1.3 mA, 2 Hz, and 300 µs
in duration of pulse was applied to Shen Men (Ht 7) for 20 minutes
once per day for three days successively. Three days later, a myocardial
tissue sample was taken for abstracting related G-proteins and corresponding
genes by using gene chip technology. Accordingly, in comparison with
the model group, after EA at Shen Men (HT), 782 differentially expressed
genes were found, of which 328 were up-regulated and 454 were down-regulated.
Compared to the normal group, 426 differentially expressed genes were
found in the EA-normal group. Among them, 217 genes were up-regulated,
and the other 209 genes were down-regulated in expression. Further
analysis showed that 21 genes were associated with the G-protein signal
transduction pathway, 15 genes had an apparent expression in all four
groups, four genes were significantly unchanged, and the remaining
two genes were differentially expressed. Of these two differentially
expressed genes, Gng8 displayed weaker and stronger expression in EA-normal
and EA-model groups, respectively, and had no expression in normal
and model groups. This suggests that these differences in Gng8 expression
were related EA at Shen Men (HT 7). Gene Prkar2b, the other of these
last two genes, showed no expression in normal and EA-normal groups,
but its expression was detectable in model and EA-model groups. This
suggests that its expression is related to MI. Thus it was concluded
that 1) EA at Shen Men (Ht 7) can affect the gene expression pathway,
and 2) Gng8 and Prkar2b may play an important role in the EA-induced
protective action on MI.
I believe that these animal studies on acupuncture and moxibustion strongly
suggest that acupuncture's therapeutic effects are not just related
to so-called nonspecific effect or placebo. Further, these five studies came
from just two issues of a single Chinese medical journal. Altogether, there
were 13 such animal studies in these two issues. Now consider how many issues
of this single journal have been published with many such animal studies.
In addition, remember that other such acupuncture animal studies are routinely
published in other Chinese acupuncture journals. In other words, there appears
to be a very large literature (albeit somewhat sequestered in Chinese) on
acupuncture's effects in animal studies. I think that if more Westerners
were aware of the existence of this body of literature, they would not be
so quick as to dismiss acupuncture's effects as simply due to placebo.
Copyright © Blue Poppy Press, 2007.
All rights reserved.
1. Available at: http://en.wikipedia.org/wiki/Placebo_(origins_of_technical_term).
May 2007: Not a valid link. Try http://en.wikipedia.org/wiki/Placebo
2. Available at: http://en.wikipedia.org/wiki/Acupuncture.
Keywords: Chinese medicine, acupuncture,
moxibustion, electroacupuncture, acupuncture efficacy, placebo, animal studies