|Year : 2019 | Volume
| Issue : 4 | Page : 181-186
Treatment of visceral pain associated with irritable bowel syndrome using acupuncture: Mechanism of action
Aleksandar Zivaljevic, Bin Shi, Elisa M S. Tam, Vahideh Toossi
New Zealand College of Chinese Medicine, Auckland, New Zealand
|Date of Submission||20-Mar-2019|
|Date of Decision||01-May-2019|
|Date of Acceptance||22-May-2019|
|Date of Web Publication||03-Dec-2019|
Dr. Vahideh Toossi
New Zealand College of Chinese Medicine, Level 2, 321 Great South Road, Greenlane, Auckland
Source of Support: None, Conflict of Interest: None
Irritable bowel syndrome (IBS) is a relatively common condition characterized by abdominal pain, among other symptoms, that significantly impacts the quality of life of IBS patients. Therapeutic treatment of IBS results in limited success, and the focus is placed on relieving patients of some of the symptoms, visceral pain in particular. Acupuncture is commonly used as a treatment modality of choice. However, the debate on whether acupuncture can be effectively used for this purpose is ongoing. In this work, we critically review the available literature to establish a potential mechanism of action in treating visceral pain in IBS using acupuncture. The sources used are Google Scholar, EBSCO, Cochrane Library and PubMed as well as Chinese database sources. The keywords used in the literature search are “acupuncture,” “IBS,” “Irritable Bowel Syndrome,” and “visceral pain.” We find that the literature strongly indicates that acupuncture, by stimulating points located on the dermatomes proximal to the spinal level of the area where the sympathetic outflow of the particular gut area affected by the pain is, can interfere with the efferent signal that transports information about the noxious stimuli and interrupt the “connectivity” between the gut and brain, and as a final result, reduce or stop IBS pain. Our findings justify that clinical trials are conducted to test the utility of acupuncture in treating abdominal visceral pain in IBS.
Keywords: Acupuncture, irritable bowel syndrome, visceral pain
|How to cite this article:|
Zivaljevic A, Shi B, S. Tam EM, Toossi V. Treatment of visceral pain associated with irritable bowel syndrome using acupuncture: Mechanism of action. World J Tradit Chin Med 2019;5:181-6
|How to cite this URL:|
Zivaljevic A, Shi B, S. Tam EM, Toossi V. Treatment of visceral pain associated with irritable bowel syndrome using acupuncture: Mechanism of action. World J Tradit Chin Med [serial online] 2019 [cited 2020 Jan 19];5:181-6. Available from: http://www.wjtcm.net/text.asp?2019/5/4/181/271964
| Introduction-Epidemiology of the Underlying Disease/disorder|| |
Irritable bowel syndrome (IBS) is a complex of symptoms attributed to the intestines including, but not limited to, abdominal pain, change in bowel function and stool form and frequency, bloating, presence of mucus in stools, and a sensation of incomplete evacuation. The symptoms are difficult to explain and are either of chronic or recurrent nature. This disorder is commonly associated with notable psychological issues, and it impacts the overall quality of life of the sufferers. Psychological issues range from emotional distress to abnormal personality features, psychiatric diagnoses, and illness behaviors.,
Levy et al. found that the cost of care of an IBS patient is 49% higher than the cost of care of a non-IBS patient in the year when IBS is diagnosed. They also found that the IBS patients make twice as many visits to the health-care professionals compared to the general population, controlled for age. This makes IBS patient significantly more expensive to the health system over the patient's lifetime compared to a non-IBS patient.
Psychiatric and psychological disorders are associated with IBS. The most prominent psychiatric disorders in IBS patients are depression, followed by anxiety and somatization disorders. Although the range and spread of psychiatric disorders are the same in general and IBS populations, the prevalence is very different. For example, Axis I psychiatric disorders are found in 40%–94% of IBS patients which is significantly higher than the general population. Although strong association has been established, these disorders are still seen as distinct to IBS and no direct causation has been proven.
Although in the study carried out by Park et al., even distribution between the genders is reported, the assumption that women are more susceptible to this condition is more prevalent in the literature.,,, The reason for this is not clear, Bommelaer et al. suggested that the differences in diagnostic tests and the higher response rates for questionnaire among women might be an explanation for this difference in distribution. The distribution between the age groups was reported mostly as even with just slightly higher prevalence in the group younger than 45.
Due to the differences in symptoms, three subclasses of IBS have been recognized: IBS-D, IBS-C, and IBS-M. The predominant symptom in IBS-D is diarrhea, in IBS-C is constipation, and in IBS-M, it is a mixture of the two. Although some population studies reported close to equal distribution of the IBS subclasses among the populations they studied, the majority of studies find that IBS-C and IBS-D are more common than IBS-M.,,
As no biomarkers are available for the diagnosis of IBS, diagnosis is almost entirely clinically symptom based. ROME IV criteria prescribes diagnostic criteria as recurrent abdominal pain that occurs at least 1 day a week in the 3 months prior to the diagnosis, associated with two or more of the following: (1) related to defecation, (2) associated with a change in the frequency of stools, and (3) associated with a change in the form of stools.
Along with the lack of predictability of bowel function, abdominal pain is considered a major contributor to the decreased quality of life in IBS patients. The pain is generally visceral in origin and chronic in nature. However, its etiology is unclear, with authors proposing several theories.
One of the theories contends that the pain is caused by a low-grade mucosal inflammation. This is supported by the findings from a group of researchers conducting military research who found that after contracting gastroenteritis, soldiers experienced IBS-like symptoms that could last for variable periods of time. It is suggested that the condition might be explained by the increase in numbers of inflammatory cells proximal to the enteric neurons as well as with the number of mast cells, especially activated or degranulating mast cells located around enteric neurons.
These symptoms were seen regardless of the etiology of the gastroenteritis (viral or bacterial). However, Spiller and Garsed found that viral gastrointestinal infections produce short-term IBS-like symptoms that include visceral pain, while the IBS-like symptoms produced by bacterial infections stay for longer. The authors called this “postinfective IBS” or PI-IBS and find that, although its prognosis is somewhat better than the prognosis of IBS, the condition can still persist for several years after the initial infection.
Another group of scientists found significantly increased immunoglobulin (Ig) G2 subclass antibody levels to Blastocystis homonis in patients with IBS. This was further investigated, and it was found that increased numbers of Blastocystis homonis were frequently demonstrated in the stool of IBS patients involved in the trial as opposed to the control group of healthy individuals. Although this correlation does not confirm causation, presence of a bacteria that is strongly suspected to cause gastrointestinal issues, and elevated levels of which are proven to cause abdominal pain,, provide a good indication that some causation might be in place.
In addition to its presence, IBS patients are also found to have hypersensitivity to visceral pain. This is experimentally confirmed by measuring rectal sensory thresholds, and those in IBS patients were found to be significantly lower than the control group. This phenomena has attracted fair attention of the scientific community,,, but it is unclear whether hypersensitivity is a direct symptom of IBS or it is a consequence of the prolonged episodes of pain that IBS patients are subjected to. According to the pathophysiology of pain, hypersensitivity to pain (hyperalgesia) is normally seen in patients as a pathophysiological consequence of the prolonged episodes of pain.,
Even though the diagnostic methods are getting more effective, the same cannot be said for the treatment methods, as no curative therapy for IBS exists at present. The available treatments treat symptoms only and mostly fall in the realm of pharmacologic treatments and psychological interventions with varying levels of success.,
Therapeutic treatment of IBS is known to result in limited success. The evidence for this is collected in numerous clinical trials where the results have shown that the placebo effects are very similar to the positive effects of the treatments., Hence, the focus in treating IBS is placed on relieving the patients from some of the symptoms and increasing their quality of life. The choice of treatment is usually between pharmacological, dietary, or psychological treatments and direct interventions, such as colonic irrigation or fecal microbiota transplantation.
| Use Of Alternative Medicine In The Treatment Of Irritable Bowel Syndrome|| |
The fact that contemporary medicine does not have a treatment that would eliminate IBS has made many patients to seek for alternative solutions. It is reported that numerous alternative options are offered to patients and that the modern communication systems, including YouTube, are utilized by the providers to disseminate information about them. Frass et al. report that the most commonly selected alternatives include chiropractic manipulation, Traditional Chinese Medicine (TCM) modalities, massage, and homeopathy among others. However, patients would also select one or more of the more controversial alternative therapy avenues, including water fasting, yoga, hypnotherapy, frequency healing, and essential oil therapy among others.
TCM modalities commonly used in the treatment of IBS are acupuncture, herbal medicine, and moxibustion. It was reported that the success of moxibustion is similar or better, when compared to the success of treatment based on pharmacological medications. For TCM herbal medicine, some authors find it not more efficient than placebo, while a greater number of authors draw a clear link between the alleviation of IBS symptoms and TCM herbal treatment.,
The evidence base on the effectiveness of acupuncture in the treatment of IBS has expanded over time. However, consensus on the level of its effectiveness has still not been reached, and debate is ongoing. One of the reasons for that is the question of study validity which calls for more comprehensive studies deploying more robust research methods. Moreover, the authors point out that the heterogeneity in terms of interventions, controls, and outcomes measured is not of help either. However, the remark has been made that the question of validity is usually raised in the meta-analyses that have not accessed Chinese scientific databases and therefore have potentially based their findings on a limited sample size.
Although large corpora of texts point out that the results achieved by acupuncture are no better than the results of placebo treatment,,,, other texts, including trials and meta-analyses, assert the opposite.,,, It is rather significant that the scientists observing the same phenomenon distant their findings this far on the spectrum and that certainly justifies further research and greater debate on the topic.
| Acupuncture – Mechanism Of Action|| |
In TCM, acupuncture is seen as a manipulation of the body's energy, as it flows through the system of energy channels called meridians. This energy is called Qi and is seen as essential to life processes. An illness is seen to be a display of Qi disturbance, a result of interruptions and imbalances in the network of meridians. This Qi disturbance further indicates an imbalance in the Yin and Yang, the two concepts that at the same time are both opposing and complementary forces that coexist in nature and are integral to regulate Qi.
The idea behind acupuncture is that insertion of fine needles in specific points located on the meridians stimulates the body to rebalance Qi and normalize bodily disharmonies. The points targeted by acupuncture are called acupoints, and their stimulation is seen as having effect on organs, with stimulation of each of the acupoints having a distinct therapeutic effect. Treatments generally include stimulation of groups of selected acupoints, selection of which is made by the practitioner and based on the observed disharmony and desired therapeutic effect.
The stimulation effect in acupuncture is traditionally achieved through manual insertion and manipulation of an acupuncture needle. The manipulation can be performed during and after insertion and is either a rotation or an up/down movement of the needle or both. This is expected to produce a de qi effect, which represents a connection of the needle and the energy flowing through the meridian that the point is related to. Physically, this connection is manifested as an aching sensation in the area around the needle by the patient and a “needle grasp” phenomenon by the acupuncturist.
In China, acupuncture has been used as a treatment choice for treating gastrointestinal disorders for 1000's of years. Although the exact mechanism remains unknown, it is assumed that the ability of acupuncture to alter acid secretion, gastrointestinal motility, and visceral pain plays an important role in improving the symptoms. The experiments carried out on animal and human subjects strongly indicate a biological foundation that acupuncture works from.
Experiments on animals have indicated that stimuli applied on certain points of skin and muscles affect functionality of some autonomic functions, including the functions of the gastrointestinal system.,,,, These points on the skin act as somatic references that convey these stimuli using proximal somatic connections to the appropriate organs, that in response alter one or more of their functions. The authors describe these reactions as somatoautonomic reflex responses.
Similar phenomenon was observed in the experiments carried out on human subjects as well. The experiment where transcutaneous electrical nerve stimulation (TENS) was used to stimulate T5-T10, and C8-T1 dermatomes has produced somatogastric reflexes exhibited as subtle vasomotor changes as well as decreased peripheral responsiveness, indicating low-level central analgesia. The dermatomes were selected based on their location in relation to where the sympathetic outflow to the particular gut area arises, satisfying the requirement for the proximity of the spinal level location of the sympathetic afferent and efferent nerves, as it was found on animals.
This physiological phenomenon has been successfully used in treating some disorders of the gastrointestinal tract. Kaada describes intervention where TENS is successfully used to treat achalasia and systemic sclerosis of the esophagus that was causing dysphagia. The result was confirmed in another experiment conducted by Guelrud et al., who also found that the mediator in this chain of reaction included a neuropeptide with inhibitory neurotransmitter activity in nonadrenergic-noncholinergic pathways, called vasoactive intestinal polypeptide.
Moreover, the existence of this mechanism is strongly indicated by experiments where magnetic resonance imaging is used to measure brain activity after and during the acupuncture treatment., The starting point for these studies was observing change in the activities of the areas of the central nervous system that previous studies,, have associated with the visceral pain experienced in IBS. The areas include anterior cingulate cortex, prefrontal cortex, insular cortex, thalamus, dorsal pons, and periaqueductal gray matter. The studies found acupuncture could induce changes in these areas, including changes in glucose metabolism in the relevant gyri as well as changes in blood pressure in the thalamus among other changes. These experiments prove not just the relationship between the stimulation of the points on the skin and physiological reactions of the brain, but also provide indications of the potential route of acupuncture pain modulation as deactivation of descending nociceptive pathways and decrease of limbic activity.
These pieces of evidence confirm “connectivity” between the points on the skin and the corresponding physiological functions, indicating what could potentially be the mechanism behind acupuncture. It is very likely that the perforation of the skin stimulates afferent points of the nerves that, through the proximal connection in the dermatomes, further stimulate sympathetic efferent nerves with the ability to control targeted physiological functions. Certainly, detailed understanding of the relevant physiological phenomena needed for interpreting these developments could not have been known by the ancient Chinese and the theory of energy flowing through the meridians sounds like a logical elucidation of this complex manifestation.
The reviewed and above-mentioned literature strongly indicates that acupuncture, by stimulating points located on the dermatomes proximal to the spinal level to the area where the sympathetic outflow of the particular gut area affected by the pain, can interfere with the efferent signal that transports information about the noxious stimuli and interrupts the “connectivity” between the gut and the brain, and as a final result, reduces or stops IBS pain.
We base the above assumption on the established fact that the pain sensation can be altered if the pain signal is interfered with. Pathophysiology of pain describes pain as noxious stimuli detected by specific receptors called nociceptors whose cell bodies are in the dorsal root ganglia and terminate in the superficial layers of the dorsal horn of the spinal cord. Here, they relay messages to the second-order neurons by activating the release of neurotransmitters. Upon reception of the signal, the second-order neurons activate the third-order neurons whose distal ends are located in the thalamus, that further activate centers in the somatosensory cortex specific to the origin of activation.
This afferent mechanism of transferring the signal from the noxious receptors to the somatosensory centers in the brain must be uninterrupted for the sensation of pain to occur. It is known that if in some way, this nociceptive transmission is interrupted, the pain sensation is altered., Noncortical modulation of pain is commonly achieved on two sites, spinal cord's dorsal horn and periaqueductal gray matter. It is found that modulation in this area can be not just suppressive to pain but to also have excitatory influence on dorsal horn neurons, producing the sensation of pain without any nociceptive transmission coming from the first-order neurons.
An example is the work of Budai and Fields where microinjections of bicuculline in the ventrolateral periaqueductal gray matter were found to led to a 60%–80% decrease in the neuronal responses to heat in rats. They also found that injection of naloxone in the same area will have an excitatory effect and will produce pain sensation without the involvement of the first-order neurons and their receptors. In addition to the use of chemical agents, periaqueductal gray matter modulation is also achieved using electrical current. An example is the experiment by Fields and Basbaum where they used electrical current to stimulate periaqueductal gray matter and produce analgesia in rats.
Our assumption is that the pain signal in the case of acupuncture will be modulated in the area of the dorsal horn where dorsal roots of the efferent first-order neurons transfer the signal to the proximal ends of the second-order neurons. However, we are not sure what the exact mechanism of the modulation will be. It might be that the signal produced by the insertion of a needle will induce secretion of endogenous opioids in the periaqueductal gray matter and induce analgesia, or it might be that the electric signals produced by the insertion of an acupuncture needle induce iontophoresis in the area of interneuronal cells in the periaqueductal gray matter, excite them and make them exhibit their inhibitory effect, similar to what electrical current does when inducing analgesia.
Although only indications of the mechanism of acupuncture action exist, the fact that the “communication” between the dermatomes and the visceral organs has been documented in animals,, and humans,,, provides a sufficient ground for our hypothesis.
| Conclusion|| |
We provide a synopsis of the IBS epidemiology before we outlined alternative treatment options that are in use today. Then, we listed acupuncture as one of the modalities of TCM used in the treatment of IBS and reviewed the literature that explores the physiological phenomena that might be underpinning its mechanism of action. In particular, we focused on the physiological phenomena that are indicated to modulate abdominal visceral pain which is the most common symptom in IBS. Our conclusion is that acupuncture potentially alters the signal that transports noxious stimuli information and interrupts gut–brain “connectivity” to reduce or stop IBS pain. This assumption needs to be clinically tested, and we suggest clinical trial (s) that would provide further evidence in support or against this assumption.
Research supported by New Zealand College of Chinese Medicine. No external grants received. The authors declare no conflict of interest.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Drossman DA, McKee DC, Sandler RS, Mitchell CM, Cramer EM, Lowman BC, et al.
Psychosocial factors in the irritable bowel syndrome. A multivariate study of patients and nonpatients with irritable bowel syndrome. Gastroenterology 1988;95:701-8.
Whitehead WE, Bosmajian L, Zonderman AB, Costa PT Jr., Schuster MM. Symptoms of psychologic distress associated with irritable bowel syndrome. Comparison of community and medical clinic samples. Gastroenterology 1988;95:709-14.
Levy RL, Von Korff M, Whitehead WE, Stang P, Saunders K, Jhingran P, et al.
Costs of care for irritable bowel syndrome patients in a health maintenance organization. Am J Gastroenterol 2001;96:3122-9.
Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: What are the causes and implications? Gastroenterology 2002;122:1140-56.
Park JM, Choi MG, Kim YS, Choi CH, Choi SC, Hong SJ, et al.
Quality of life of patients with irritable bowel syndrome in Korea. Qual Life Res 2009;18:435-46.
Bommelaer G, Dorval E, Denis P, Czernichow P, Frexinos J, Pelc A, et al.
Prevalence of irritable bowel syndrome in the French population according to the Rome I criteria. Gastroenterol Clin Biol 2002;26:1118-23.
Hillilä MT, Färkkilä MA. Prevalence of irritable bowel syndrome according to different diagnostic criteria in a non-selected adult population. Aliment Pharmacol Ther 2004;20:339-45.
Katsinelos P, Lazaraki G, Kountouras J, Paroutoglou G, Oikonomidou I, Mimidis K, et al.
Prevalence, bowel habit subtypes and medical care-seeking behaviour of patients with irritable bowel syndrome in Northern Greece. Eur J Gastroenterol Hepatol 2009;21:183-9.
Tan YM, Goh KL, Muhidayah R, Ooi CL, Salem O. Prevalence of irritable bowel syndrome in young adult Malaysians: A survey among medical students. J Gastroenterol Hepatol 2003;18:1412-6.
Grundmann O, Yoon SL. Irritable bowel syndrome: Epidemiology, diagnosis and treatment: An update for health-care practitioners. J Gastroenterol Hepatol 2010;25:691-9.
Thompson WG, Irvine EJ, Pare P, Ferrazzi S, Rance L. Functional gastrointestinal disorders in Canada:First population-based survey using Rome II criteria with suggestions for improving the questionnaire. Dig Dis Sci 2002;47:225-35.
Halland M, Saito YA. Irritable bowel syndrome: New and emerging treatments. BMJ 2015;350:h1622.
Ghoshal UC. Pros and cons while looking through an Asian window on the Rome IV criteria for irritable bowel syndrome: Pros. J Neurogastroenterol Motil 2017;23:334-40.
Musial F, Häuser W, Langhorst J, Dobos G, Enck P. Psychophysiology of visceral pain in IBS and health. J Psychosom Res 2008;64:589-97.
Pimentel M, Lembo A, Schoenfeld P, Cash B. Irritable bowel syndrome: Pathophysiology and goals of therapy. Med Roundtable Gen Med Ed 2014;1:248-56.
Spiller R, Garsed K. Postinfectious irritable bowel syndrome. Gastroenterology 2009;136:1979-88.
Hussain R, Jaferi W, Zuberi S, Baqai R, Abrar N, Ahmed A, et al.
Significantly increased IgG2 subclass antibody levels to Blastocystis hominis
in patients with irritable bowel syndrome. Am J Trop Med Hyg 1997;56:301-6.
Yakoob J, Jafri W, Jafri N, Khan R, Islam M, Beg MA, et al.
Irritable bowel syndrome: In search of an etiology: Role of Blastocystis hominis
. Am J Trop Med Hyg 2004;70:383-5.
Singh M, Suresh K, Ho LC, Ng GC, Yap EH. Elucidation of the life cycle of the intestinal protozoan Blastocystis hominis
. Parasitol Res 1995;81:446-50.
Taamasri P, Mungthin M, Rangsin R, Tongupprakarn B, Areekul W, Leelayoova S. Transmission of intestinal blastocystosis related to the quality of drinking water. Southeast Asian J Trop Med Public Health 2000;31:112-7.
Kaya S, Cetin ES, Aridoǧan BC, Arikan S, Demirci M. Pathogenicity of Blastocystis hominis
, a clinical reevaluation. Turkiye Parazitol Derg 2007;31:184-7.
Qadri SM, al-Okaili GA, al-Dayel F. Clinical significance of Blastocystis hominis
. J Clin Microbiol 1989;27:2407-9.
Bouin M, Plourde V, Boivin M, Riberdy M, Lupien F, Laganière M, et al.
Rectal distention testing in patients with irritable bowel syndrome: Sensitivity, specificity, and predictive values of pain sensory thresholds. Gastroenterology 2002;122:1771-7.
Kanazawa M, Palsson OS, Thiwan SI, Turner MJ, van Tilburg MA, Gangarosa LM, et al.
Contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits. Am J Gastroenterol 2008;103:2550-61.
Verne GN, Robinson ME, Price DD. Hypersensitivity to visceral and cutaneous pain in the irritable bowel syndrome. Pain 2001;93:7-14.
LaMotte RH, Thalhammer JG, Torebjörk HE, Robinson CJ. Peripheral neural mechanisms of cutaneous hyperalgesia following mild injury by heat. J Neurosci 1982;2:765-81.
Meyer RA, Campbell JN. Myelinated nociceptive afferents account for the hyperalgesia that follows a burn to the hand. Science 1981;213:1527-9.
Zijdenbos IL, de Wit NJ, van der Heijden GJ, Rubin G, Quartero AO. Psychological treatments for the management of irritable bowel syndrome. Cochrane Database Syst Rev 2009;(1):CD006442
Krarup AL, Engsbro ALØ, Fassov J, Fynne L, Christensen AB, Bytzer P, et al.
Danish national guideline: Diagnosis and treatment of irritable bowel syndrome. Dan Med J 2017;64. pii: C5382.
Flik CE, Bakker L, Laan W, van Rood YR, Smout AJ, de Wit NJ. Systematic review: The placebo effect of psychological interventions in the treatment of irritable bowel syndrome. World J Gastroenterol 2017;23:2223-33.
Hod K, Sperber AD, Ron Y, Boaz M, Dickman R, Berliner S, et al
. A doubleblind, placebocontrolled study to assess the effect of a probiotic mixture on symptoms and inflammatory markers in women with diarrheapredominant IBS. Neurogastroenterol Motil 2017;29:e13037.
Camilleri M, Boeckxstaens G. Dietary and pharmacological treatment of abdominal pain in IBS. Gut 2017;66:966-74.
Hsu HH, Leung WH, Hu GC. Treatment of irritable bowel syndrome with a novel colonic irrigation system: A pilot study. Tech Coloproctol 2016;20:551-7.
Holvoet T, Joossens M, Wang J, Boelens J, Verhasselt B, Laukens D, et al.
Assessment of faecal microbial transfer in irritable bowel syndrome with severe bloating. Gut 2017;66:980-2.
Balagoni H, Mando R, Reddy K, Bansal A, Aregbe A, Bajaj K, et al.
You Tube as a source of information for irritable bowel syndrome: A critical appraisal. ETSU Fac Works 2017. Available from: https://dc.etsu.edu/etsu-works/324
. [Last accessed on 2017 Jul 12].
Frass M, Strassl RP, Friehs H, Müllner M, Kundi M, Kaye AD. Use and acceptance of complementary and alternative medicine among the general population and medical personnel: A systematic review. Ochsner J 2012;12:45-56.
Tang B, Zhang J, Yang Z, Lu Y, Xu Q, Chen X, et al.
Moxibustion for diarrhea-predominant irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med 2016;2016:5105108.
Anastasi JK, McMahon DJ, Kim GH. Symptom management for irritable bowel syndrome: A pilot randomized controlled trial of acupuncture/moxibustion. Gastroenterol Nurs 2009;32:243-55.
Park JW, Lee BH, Lee H. Moxibustion in the management of irritable bowel syndrome: Systematic review and meta-analysis. BMC Complement Altern Med 2013;13:247.
Leung WK, Wu JC, Liang SM, Chan LS, Chan FK, Xie H. Treatment of diarrhea-predominant irritable bowel syndrome with traditional Chinese herbal medicine: A randomized placebo-controlled trial. Am J Gastroenterol 2006;101:1574-80.
Bensoussan A, Talley NJ, Hing M, Menzies R, Guo A, Ngu M, et al.
Treatment of irritable bowel syndrome with Chinese herbal medicine: A randomized controlled trial. JAMA 1998;280:1585-9.
Wang G, Li TQ, Wang L, Xia Q, Chang J, Zhang Y, et al.
Tong-Xie-Ning, a Chinese herbal formula, in treatment of diarrhea-predominant irritable bowel syndrome: A prospective, randomized, double-blind, placebo-controlled trial. Chin Med J (Engl) 2006;119:2114-9.
Ernst E, Pittler MH, Wider B, Boddy K. Acupuncture: Its evidence-base is changing. Am J Chin Med 2007;35:21-5.
Lim B, Manheimer E, Lao L, Ziea E, Wisniewski J, Liu J, et al
. Acupuncture for treatment of irritable bowel syndrome. Cochrane Database Syst Rev 2006;(4):CD005111.
Lui S, Smith EJ, Terplan M. Heterogeneity in search strategies among cochrane acupuncture reviews: Is there room for improvement? Acupunct Med 2010;28:149-53.
Fireman Z, Segal A, Kopelman Y, Sternberg A, Carasso R. Acupuncture treatment for irritable bowel syndrome. A double-blind controlled study. Digestion 2001;64:100-3.
Lembo AJ, Conboy L, Kelley JM, Schnyer RS, McManus CA, Quilty MT, et al.
A treatment trial of acupuncture in IBS patients. Am J Gastroenterol 2009;104:1489-97.
Schneider A, Enck P, Streitberger K, Weiland C, Bagheri S, Witte S, et al.
Acupuncture treatment in irritable bowel syndrome. Gut 2006;55:649-54.
Chao GQ, Zhang S. Effectiveness of acupuncture to treat irritable bowel syndrome: A meta-analysis. World J Gastroenterol 2014;20:1871-7.
Manheimer E, Cheng K, Wieland LS, Min LS, Shen X, Berman BM, et al
. Acupuncture for treatment of irritable bowel syndrome. Cochrane Database Syst Rev 2012;(5):CD005111.
Rafiei R, Ataie M, Ramezani MA, Etemadi A, Ataei B, Nikyar H, et al.
A new acupuncture method for management of irritable bowel syndrome: A randomized double blind clinical trial. J Res Med Sci 2014;19:913-7.
Zhao C, Mu J, Cui Y, Yang L, Ma X, Qi L. Meta-analysis on acupuncture and moxibustion for irritable bowel syndrome. Chin Arch Tradit Chin Med 2010;5:26.
Kaptchuk T. The Web That Has No Weaver: Understanding Chinese Medicine. New York, NY: BookBaby; 2014. p. 455.
O'Connor J, Bensky D. Acupuncture: A Comprehensive Text. Vista, CA: Eastland Press; 1981. p. 774.
Langevin HM, Yandow JA. Relationship of acupuncture points and meridians to connective tissue planes. Anat Rec 2002;269:257-65.
Takahashi T. Acupuncture for functional gastrointestinal disorders. J Gastroenterol 2006;41:408-17.
Jansson G. Effect of reflexes of somatic afferents on the adrenergic outflow to the stomach in the cat. Acta Physiol Scand 1969;77:17-22.
Kametani H, Sato A, Sato Y, Simpson A. Neural mechanisms of reflex facilitation and inhibition of gastric motility to stimulation of various skin areas in rats. J Physiol 1979;294:407-18.
Kehl H. Studies of reflex communications between dermatomes and jejunum. J Am Osteopath Assoc 1975;74:667-9.
Koizumi K, Sato A, Terui N. Role of somatic afferents in autonomic system control of the intestinal motility. Brain Res 1980;182:85-97.
Sato A, Sato Y, Shimada F, Torigata Y. Changes in gastric motility produced by nociceptive stimulation of the skin in rats. Brain Res 1975;87:151-9.
Camilleri M, Malagelada JR, Kao PC, Zinsmeister AR. Effect of somatovisceral reflexes and selective dermatomal stimulation on postcibal antral pressure activity. Am J Physiol 1984;247:G703-8.
Kaada B. Successful treatment of esophageal dysmotility and Raynaud's phenomenon in systemic sclerosis and achalasia by transcutaneous nerve stimulation. Increase in plasma VIP concentration. Scand J Gastroenterol 1987;22:1137-46.
Guelrud M, Rossiter A, Souney PF, Mendoza S, Mujica V. The effect of transcutaneous nerve stimulation on sphincter of Oddi pressure in patients with biliary dyskinesia. Am J Gastroenterol 1991;86:581-5.
Hui KK, Liu J, Makris N, Gollub RL, Chen AJ, Moore CI, et al.
Acupuncture modulates the limbic system and subcortical gray structures of the human brain: Evidence from fMRI studies in normal subjects. Hum Brain Mapp 2000;9:13-25.
Wu MT, Hsieh JC, Xiong J, Yang CF, Pan HB, Chen YC, et al.
Central nervous pathway for acupuncture stimulation: Localization of processing with functional MR imaging of the brain – preliminary experience. Radiology 1999;212:133-41.
Bonaz B, Baciu M, Papillon E, Bost R, Gueddah N, Le Bas JF, et al.
Central processing of rectal pain in patients with irritable bowel syndrome: An fMRI study. Am J Gastroenterol 2002;97:654-61.
Mertz H, Morgan V, Tanner G, Pickens D, Price R, Shyr Y, et al.
Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention. Gastroenterology 2000;118:842-8.
Silverman DH, Munakata JA, Ennes H, Mandelkern MA, Hoh CK, Mayer EA. Regional cerebral activity in normal and pathological perception of visceral pain. Gastroenterology 1997;112:64-72.
Ma XP, Hong J, An CP, Zhang D, Huang Y, Wu HG, et al.
Acupuncture-moxibustion in treating irritable bowel syndrome: How does it work? World J Gastroenterol 2014;20:6044-54.
Tillisch K. Complementary and alternative medicine for functional gastrointestinal disorders. Gut 2006;55:593-6.
Vanderah TW. Pathophysiology of pain. Med Clin North Am 2007;91:1-2.
Wall PD. The role of substantia gelatinosa as a gate control. Res Publ Assoc Res Nerv Ment Dis 1980;58:205-31.
Willis WD Jr. Dorsal horn neurophysiology of pain. Ann N
Y Acad Sci 1988;531:76-89.
Ohara PT, Vit JP, Jasmin L. Cortical modulation of pain. Cell Mol Life Sci 2005;62:44-52.
Budai D, Fields HL. Endogenous opioid peptides acting at mu-opioid receptors in the dorsal horn contribute to midbrain modulation of spinal nociceptive neurons. J Neurophysiol 1998;79:677-87.
Fields HL, Basbaum AI. Brainstem control of spinal pain-transmission neurons. Annu Rev Physiol 1978;40:217-48.