Neuromodulation: Technology at the Neural Interface

Received: December 22, 2009 First revision: March 3, 2010 Accepted: May 7, 2010

(onlinelibrary.wiley.com) DOI: 10.1111/j.1525-1403.2010.00295.x

Mechanism of Acupuncture on
Neuromodulation in the Gut—A Review ner_295 8..12

Toku Takahashi, MD, PhD

Introduction: Acupuncture has been used for treating various gastrointestinal (GI) diseases. However, the mechanism of acu-
puncture remains unclear.
Methods: The aim of this article is to review the published literature on the mechanism of acupuncture on neuromodulation in
the gut.
Results: Acupuncture treatment involves the insertion of thin needles into the skin and underlying muscle and the subsequent
stimulation of the needles manually or electrically. Thus, acupuncture stimulates the somatic afferent nerves of the skin and
muscles. The somatic sensory information from the body is carried to the cortex area of the brain. Somatic sensory fibers also
project to the various nuclei at the brain stem and hypothalamus. Via somato-autonomic reflex, acupuncture modulates various
biomechanical responses, such as prokinetic, antiemetic, and anti-nociceptive effects.
Conclusion: According to traditional Chinese medicine, “Acupuncture is believed to restore the balance of Yin and Yang.” This can
be translated into the Western medicine terminology that “Acupuncture modulates the imbalance between the parasympathetic
and sympathetic activity.” Acupuncture may be effective in patients with functional GI disorders because of its effects on GI motility
and visceral pain.

Keywords: Muscle contraction, neurostimulation, nociceptive pain, opioid, peripheral nerve stimulation, transcutaneous electri-
cal nerve stimulation, vagal nerve stimulation
Conflict of Interest: The author declared no conflicts of interest.

INTRODUCTION A person’s health is influenced by the flow of Qi in the body, in

Acupuncture has been in practice in China for more than 3000 years.
Acupuncture has been used for treating various gastrointestinal (GI)
diseases (1,2), including gastroparesis (3,4), functional dyspepsia
(5,6), irritable bowel syndrome (7–9), constipation (10,11), diarrhea
(12,13), and visceral hypersensitivity (14).
Acupuncture was first introduced to the American public in 1972.
However, acupuncture has not been well accepted by the physi-
cians in the Western countries. This may be due, in part, to the
mysterious and unexplainable mechanisms of acupuncture. In this
review, the possible mechanisms of acupuncture treatment are dis-
cussed from the view point of Western medicine, rather than
through the concepts of traditional Chinese medicine.
ENERGY FLOW (QI) OR SOMATO-AUTONOMIC
REFLEX?
Energy Flow and Meridians—Concept of Traditional
Chinese Medicine
According to traditional Chinese medicine concepts, the energy
force, known as Qi (pronounced Chee), runs through the body. This
Qi energy enters the body through specific acupuncture points and
flows to deeper organ structures, bringing life-giving nourishment
of a subtle energetic nature. Meridians are classified on the basis of
the direction in which Qi flows on the surface of the body. There are
about 20 meridians, which include the 12 regular and 8 extraordi-
8
combination with the universal forces of Yin and Yang. If the flow of
Qi is insufficient, unbalanced, or interrupted, Yin and Yang become
unbalanced and illness may occur (15). However, these ancient
traditions/concepts of Qi and meridians have no counterpart in
modern studies of chemistry, biology, and physics. To date scientists
have been unable to find evidence that supports their existence.
Acupuncture is believed to restore the balance of Yin and Yang.
Acupuncture loci, also know as acupoints, are the skin needling
points used for acupuncture treatment. In humans, more than 300
acupoints are located along the meridians. Acupoints are thought
to be the specific points reflecting visceral conditions and organs
(16). Despite the fact that the specific acupoints are used for treating
specific symptoms and/or diseases, it is not fully understood how
their specificity applies and how the needling at acupoints works.
Ahn et al. conducted a systematic review of studies directly evalu-
ating the electrical characteristics of acupuncture structures and
Address correspondence to: Toku Takahashi, MD, PhD, Research Service 151,
Zablocki VA Medical Center, 5000 West National Avenue, Milwaukee, WI 53295,
USA. Email: ttakahashi@mcw.edu
Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical
Center, Milwaukee, WI, USA
For more information on author guidelines, an explanation of our peer review
process, and conflict of interest informed consent policies, please go to http://

nary meridians. www.wiley.com/bw/submit.asp?ref=1094-7159&site=1

www.neuromodulationjournal.com © 2010 International Neuromodulation Society Neuromodulation 2011; 14: 8–12


appropriate controls. There was no clear evidence to demonstrate
the existence of acupuncture points or meridians. Present evidence
does not conclusively support that acupuncture points or meridians
are electrically distinguishable (17).
Somato-Autonomic Reflex
Acupuncture treatment involves the insertion of thin needles into
the skin and underlying muscle layer. In traditional acupuncture
procedure, these acupuncture needles are twisted right and left at
0.5–1 second intervals. Most recently, acupuncture needles are
stimulated by electricity under various frequencies of 1–100 Hz
(Electroacupuncture, EA). Thus, the procedure may stimulate the
somatic afferent nerves of the skin and muscles.
It has been demonstrated that somatic afferents from the skin
and muscle are involved in the control of various autonomic func-
tions. In 1913, Lehman reported that electrical stimulation of the
central part of the sciatic nerve inhibits intestinal motility and that
the splanchnic nerve is responsible for mediating the inhibitory
response in dogs (18). Electrical stimulations of the hind limb stimu-
late gastric motility via somatic afferents in cats (19).
More details of neural mechanisms of cutaneo-GI motility reflexes
have been studied in rats during the period from 1975–1980.
Sensory stimulation of the abdominal skin by pinching inhibits
gastric motility by increasing gastric sympathetic efferent nerve
activity in rats (20,21). In contrast, pinching the hind paw enhances
gastric motility by exciting gastric vagal efferent nerve activity (22).
In healthy humans, transcutaneous electrical nerve stimulation
applied to the hand and abdomen reduces antral motility (23).
These studies provide good evidence indicating the importance of
cutaneous input in autonomic control of GI functions.
The nucleus tractus solitarius (NTS) is the primary brain stem relay
for visceral information from cardiovascular, respiratory, and GI
systems. In addition, recent studies indicate that the NTS also
receives somatic afferent inputs (24,25). Electrophysiological study
demonstrated that the NTS receives input from low- and high-
threshold cutaneous mechanoreceptors. NTS neurons are activated
by the rhythmic and sustained muscle stretch of the hind limb (26).
Neurons of the NTS and the spinal cord were labeled by injection of
neuroanatomical tracers to the acupoints of hind limb (ST-36) in rats
(27). Acupuncture at the facial acupoints increases the number of
c-Fos immunopositive cells in the NTS in rats (28). Therefore, it is
highly likely that somatic stimulation induced by acupuncture is
conveyed to the NTS.
The NTS is adjacent to the dorsal motor nucleus of vagi (DMV) and
both compose the dorsal vagal complex. The dorsal vagal complex
integrates vago-vagal reflex, which plays a major role in regulation
of GI function (29,30). The NTS neurons also project to the rostral
ventrolateral medulla (RVLM) of the brain stem (31–33). The RVLM
neurons provide drive to the sympathetic preganglionic neurons in
the intermediolateral nucleus of the spinal cord (34). Thus, once NTS
neurons are stimulated by acupuncture autonomic nerve function is
altered via the activation of the DMV and/or RVLM.
MECHANISM OF ACUPUNCTURE ON
GI FUNCTION
Effects of Acupuncture on GI Motility in Normal Conditions
Among the more than 300 acupoints, several special points have
been used for treating GI symptoms. Acupoint of ST-36 is one of the
most effective points, with a wide range of effects for analgesia,
www.neuromodulationjournal.com © 2010 International Neuromodulation Society
ACUPUNCTURE ON NEUROMODULATION
immunity, homeostasis, and GI disorders. ST-36 is located near the
knee joint approximately 10 mm lateral to the anterior tubercle of
the tibia in humans. Acupoint of ST-25 is used for treating chronic
colitis and diarrhea (35,36). ST-25 is located 50 mm lateral to the
umbilicus on the abdomen in humans.
It is well known that acupuncture has regional specific effects.
Acupuncture at the hind limbs stimulates gastric motility (37–39),
while acupuncture at the abdomen inhibits gastric motility
(37,39,40) in rats. The excitatory gastric responses to the hind limb
are abolished by bilateral vagotomy in rats (37–39). In contrast, the
inhibitory gastric responses to abdomen are abolished by sympa-
thetic nerve dissection in rats (37,40). Acupuncture on the hind
limbs increases vagus discharges, while acupuncture on the
abdomen increases sympathetic discharges in rats (37,39).
Sympathetic and parasympathetic activity can be evaluated by
heart rate variability (HRV) analysis in conscious animals noninva-
sively. The power in the high frequency (HF) band of HRV represents
parasympathetic activities in rats (41,42) and humans (43). In con-
trast, the power in the low frequency (LF) band of HRV represents
sympathetic activities in rats (41,42) and a combination of sympa-
thetic and parasympathetic activities in humans (43), respectively.
Electroacupuncture at ST-36 decreases, while EA at ST-25
increases the ratio of LF/HF in rats (44). These studies suggest that
inhibitory gastric responses to the abdomen are mediated via sym-
pathetic nerves, while the excitatory gastric responses to the hind
limb are mediated via the vagus nerves.
However, the mechanism of regional differences of acupuncture
points has not been fully studied. It has been suggested that
acupuncture-evoked afferent input converge in several nuclei in the
brain stem, such as the RVLM (45,46), the NTS (26–28,47), the DMV
(38,47), and Barrington’s nucleus (48).
Electroacupuncture at ST-36 increases the number of c-Fos
immunopositive cells at the DMV and the medio-caudal and caudal
part of the NTS, while EA at ST-25 increases the number of c-Fos
immunopositive cells at the RVLM and medio-caudal part of the NTS
in rats. This suggests that somatic afferents activated by EA at ST-36
is conveyed to the medio-caudal and caudal NTS and stimulates the
DMV neurons. In contrast, somatic afferents activated by EA at ST-25
is conveyed to the medio-caudal NTS and stimulates the RVLM
neurons (49). Thus, EA at ST-25 inhibits gastric motility via the
somatosensory–NTS–RVLM–sympathetic efferent pathway. In con-
trast, EA at ST-36 stimulates gastric motility via the somatosensory–
NTS–DMV–parasympathetic efferent pathway.
In addition to the NTS, DMV, and RVLM, acupuncture may activate
some other nuclei in the brain. EA at PC-6 activates neurons in the
arcuate (ARC) nucleus and periaqueductal gray (PAG) and inhibits
the activity of RVLM, suggesting the existence of ARC-PAG-RVLM
neuronal pathway in mediating EA inhibition on visceral excitatory
cardiovascular reflexes (50).
Even though the study focuses on the cardiovascular system (50),
similar mechanisms might be utilized to produce the effects of EA
on GI motor function. It has been shown that the PAG is responsible
for mu receptor agonist- and neurotensin-induced inhibition of
intestinal transit (51).
The verification of neural pathway may contribute to the mecha-
nisms of the regional difference of acupuncture in regulating GI
motor function. Migrating motor complex is well characterized by
the appearance of GI contractions in the interdigestive state. In a
canine study, combined EA at ST-36 and PC-6 (wrists) enhances the
interdigestive gastric migrating motor complex (52). EA at ST-36 and
PC-6 accelerates gastric emptying and increases the regularity of
9
gastric slow waves in the stomach (53).
Neuromodulation 2011; 14: 8–12
 TAKAHASHI
The stimulatory effect of EA on gastric motility is associated with
increased vagal activity in dogs (53). There has been no direct evi-
dence reported that EA stimulates vagal activity in humans. Acu-
puncture at ST-36 increases the plasma pancreatic polypeptide
levels in humans (54). As pancreatic polypeptide release is depen-
dent on vagal activity, this supports the notion that acupuncture at
ST-36 may stimulate the vagal activity in humans. EA at ST-36 accel-
erates colonic transit and stimulates distal colonic motility in rats
(48,55). The stimulatory effect of EA on distal colonic motility is
mediated via the activation of Barrington’s nucleus of the pons and
parasympathetic-pelvic nerves (48).
Effects of Acupuncture on GI Motility in Stressful Conditions
It is well known that various stressors delay gastric emptying via
hypothalamic corticotropin-releasing factor (CRF). Released CRF
inhibits parasympathetic activity and/or stimulates sympathetic
activity, resulting in delayed gastric emptying (56,57). Animal
studies demonstrated that acupuncture improves various stress-
induced physiological responses (58–60).
Delayed gastric emptying induced by restraint stress or central
administration of CRF is restored by EA at ST-36 in rats. The stimu-
latory effect of EA on stress-induced delay of gastric emptying is
antagonized by pretreatment with intracisternal (ic) injection of a
glutamate receptor antagonist. This suggests that EA at ST-36 stimu-
lates glutaminergic transmission at the brainstem resulting in
improvement of stress-induced delay of gastric emptying in rats
(61).
Heart rate and LF component are increased in response to
restraint stress, suggesting increased activity of sympathetic tone
during stress loading. EA at ST-36 attenuates the elevated LF com-
ponent and increases the HF component in response to stress
loading (42). This suggests that EA at ST-36 stimulates parasympa-
thetic activity and inhibits sympathetic activity under the restraint
stress.
According to traditional Chinese medicine, “Acupuncture is
believed to restore the balance of Yin and Yang.” This can be trans-
lated into the Western medicine terminology that “Acupuncture
modulates the imbalance between parasympathetic and sympa-
thetic activity.”
Effects of Acupuncture on Emesis
Acupoint of PC-6 has been used for nausea and vomiting. PC-6 is
located in the groove caudal to the flexor carpi radialis and cranial to
the superficial digital flexor muscles. A committee of the National
Institute of Health published a report on the indications of acupunc-
ture in November 1997. The summary of the consensus statement
indicates that there is clear evidence that acupuncture treatment is
effective on postoperative and chemotherapy-induced nausea and
vomiting (62). In 1987, Dundee et al. reported that acupuncture at
PC-6 decreases cisplatin-associated nausea and vomiting (63). A
clinical study also demonstrated that EA at PC-6 significantly inhib-
its the postoperative nausea and vomiting after the surgery (64,65).
Electroacupuncture at PC-6 reduces gastric tachyarrhymia in
vection-induced motion sickness in healthy volunteers (66). Com-
bined acupuncture at ST-36 and PC-6 increases the percentage of
regular slow waves, resulting in the normalization of arrhythmia in
healthy humans (67).
However, the mechanisms of antiemetic effect of acupuncture
need to be elucidated. Level of plasma arginine vasopressin is
10
rapidly elevated in response to diverse emetic stimuli such as
www.neuromodulationjournal.com © 2010 International Neuromodulation Society
motion stimuli (68) and anticancer drugs (69,70). Intravenous injec-
tion of vasopressin results in vomiting and retching in humans
(68,71) and dogs (72,73). Acupuncture at ST-36 and PC-6 attenuates
symptom scores of emesis induced by vasopressin infusion in dogs
(73). Retrograde propulsive movement is highly associated with the
frequency of retching and vomiting. EA at PC-6 reduces the fre-
quency of retrograde propulsive movement induced by vasopressin
in dogs (74).
Opioids have dual effects: an antiemetic effect as well as an
emetic effect. It has been shown that central opioid plays a major
role in mediating antiemetic effect (75). The emetic effect is medi-
ated via the chemoreceptor trigger zone (CTZ), whereas the anti-
emetic effect is mediated via the vomiting center (75–77).
The CTZ is contained in the area postrema on the caudal margin
of the forth ventricles. As area postrema has no blood brain barrier,
naloxone methiodide (a peripheral opioid antagonist) can antago-
nize the emetic effect of opioid mediated via the CTZ. In contrast,
the vomiting center is deeply located beneath the solitary tract of
the caudal brain stem. Both the emetic and antiemetic effects of
opioid can be blocked by naloxone, because naloxone can cross the
blood brain barrier (77).
Naloxone hydrochloride, but not naloxone methiodide, abolishes
the antiemetic effect of EA at PC-6 in dogs (74). This suggests that
the antiemetic effect of EA at PC-6 is mediated via the central opioid
pathway.
Effects of Acupuncture on Visceral Pain
It has been well demonstrated that the analgesic effect of acupunc-
ture is mediated by an endogenous opioid pathway (5,78). The
painful sensation induced by rectal distension is attenuated by EA at
ST-36 in dogs. The anti-nociceptive effect of EA at ST-36 is abolished
by pretreatment with naloxone, but not naloxone methiodide. This
suggests that EA at ST-36 reduces visceral pain via a central opioid
pathway (79).
Opioid-induced anti-nociception is mediated by a pathway from
the PAG to the various brain nuclei. Recent research has docu-
mented that opioids are likely to exert direct effects on PAG projec-
tion neurons through both delta- and mu-opioid receptors (80). EA
can induce the expression of opioid peptides and opioid receptors
in the CNS (81,82).
Using functional magnetic resonance imaging, acupuncture
modulation in CNS structures can be studied noninvasively in
humans, allowing for comparison with animal studies. The PAG and
cortical areas responds to manual acupuncture at LI-4 (hand), while
sham acupuncture results in reduced levels of the PAG and cortical
activity (83). EA at ST-36 modulates activity in the substantia nigra,
nucleus raphe magnus, locus ceruleus, nucleus cuneiformis, and the
PAG. Activation in the ventrolateral PAG is greater for EA at ST-36,
compared with sham EA (84).
CONCLUSION
The mechanisms behind the beneficial effects of acupuncture can
be explained by Western medicine terminology. Acupuncture
stimulation of somato sensory neurons activates various nuclei at
the CNS, including the NTS, DMV, RVLM, and PAG, etc. Activation of
the NTS, DMV, and RVLM modulates the imbalance between sym-
pathetic and parasympathetic activity. Opioid released from the
PAG is involved in mediating antiemetic and anti-nociceptive effects
of acupuncture.
Neuromodulation 2011; 14: 8–12

Functional GI diseases are common in the general population
with a reported prevalence of 25–40%. Functional GI disorders are
the multifactorial disorders in which the pathophysiological mecha-
nisms are variably combined in different patients. The motor dys-
function of GI tract and visceral hypersensitivity are considered to
be especially important factors. Acupuncture may be effective in
patients with functional GI disorders because acupuncture has been
shown to alter GI motility and visceral pain.
Authorship Statements
Dr. Takahashi designed and conducted the study, including data
collection and data analysis. He prepared the manuscript.
How to Cite this Article:
Takahashi T. 2010. Mechanism of Acupuncture on Neu-
Romodulation in the Gut—A Review.
Neuromodulation 2011; 14: 8–12
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COMMENTS
The author provides interesting insights about mechanisms and path-
ways underlying acupuncture treatment for gastrointestinal diseases.
He describes mechanisms of acupuncture by using the research and
terminology that is more common in Western medicine. While the
author focuses on gastrointestinal diseases, acupuncture may utilize
similar mechanisms and pathways to treat not only visceral pain but
also autonomic reflexes. This is based on the work of Longhurst’s team
(Li et al., 2009) and Taché et al. (1990) who showed that the periaque-
ductal gray is involved in autonomic reflexes as well as the visceral pain
described in the present article. In fact, Taché et al. showed that the
periaqueductal gray matter is a site that is responsible for mu receptor
agonist- and neurotensin-induced inhibition of intestinal transit. The
report by Longhurst’s team (2009) also shows that the ventrolateral
periaqueductal gray is required for arcuate nucleus inhibition of rostral
ventrolateral medullary neuronal activation and subsequent activation
of electroacupuncture-related cardiovascular reflexes. Even though
their study focuses on the cardiovascular system, similar mechanisms
might be utilized to produce the effects of electroacupuncture on
gastric function.
Robert D. Foreman, PhD
Professor and Chair
Department of Physiology
College of Medicine
University of Oklahoma Health Sciences Center
Oklahoma City, OK, USA
1. Li P, Tjen-A-Looi SC, Guo ZL, Fu LW, Longhurst JC. Long-loop pathways in cardiovascular
electroacupuncture responses. J Appl Physiol 2009 Feb;106(2):620–630.
2. Taché Y, Garrick T, Raybould H. Central nervous system action of peptides to influence
gastrointestinal motor function. Gastroenterology 1990 Feb;98(2):517–528.
***
Acupuncture does not work to cure specific organic diseases. The
mechanism of acupuncture intervention is best described as neuro-
modulation of disordered function back to the normal physiological
status. This article touches the basics of acupuncture.
JS Han, MD
Peking University
Neuroscience Research Institute
Beijing, China
***
The effects of acupuncture on the modulation of autonomic nervous
system dysfunction may be a relevant basis for the treatment of the
patients with functional gastrointestinal disorders. The author of this
review makes a case for the use of acupuncture in patients with visceral
pain and functional GI disorders by “connecting the dots” between
numerous basic science studies and likely indications for the use of
acupuncture in humans.
Leonardo Kapural, MD, PhD
Director, Clinical Research, Pain Management Department
Cleveland Clinic Foundation
Associate Professor of Anesthesiology
CCLCM of Case Western University
Cleveland, OH, USA
Comments not included in the Early View version of this paper.
Neuromodulation 2011; 14: 8–12