Visceral pain, i.e., pain originating from the thoracic, abdominal, or pelvic regions, is a noticeable symptom associated with various clinical conditions [
Acupuncture has been used to treat various pain disorders, including visceral pain, and has shown considerable effects on pain relief with only rare cases of adverse events. Many studies have explored the treatment mechanism of acupuncture for pain relief in general, and it is reported that acupuncture alleviates pain mainly by regulating the levels of endogenous opioids, serotonin, and norepinephrine and by inhibiting visceral nociceptors, inflammatory cytokines, and CNS activation [
In this review, we aimed to provide an integrative understanding of the mechanisms behind the effects of acupuncture therapy on visceral pain in both human and animal subjects, and we suggest directions that can be adopted for future research.
We searched through electronic records in PubMed, EMBASE, MEDLINE, and the Cochrane Library using the keywords “visceral,” “pain,” “hyperalgesia,” “algesia,” “acupuncture,” “electroacupuncture,” and “acupoint.” The search terms and strategies were modified for each individual database (Table
Search terms used in each database.
Database | Search terms |
---|---|
PUBMED | (acupuncture [MeSH Terms] OR acupuncture [All Fields] OR acupoint [All Fields] OR electroacupuncture [MeSH Terms] OR electroacupuncture [All Fields]) AND (“visceral pain” [MeSH Terms] OR “visceral pain” [All Fields] OR (visceral [All Fields] AND (pain [All Fields] OR pain [MeSH Term])) OR (visceral [All Fields] AND (hyperalgesia [All Fields] OR hyperalgesia [MeSH Terms]))) |
EMBASE | visceral AND (“pain”/exp OR pain OR “hyperalgesia”/exp OR hyperalgesia OR algesia) AND (“acupuncture”/exp OR acupuncture OR “electroacupuncture”/exp OR electroacupuncture OR acupoint) |
MEDLINE | (visceral and (pain or hyperalgesia or algesia) and (acupuncture or electroacupuncture or acupoint)).mp. |
Cochrane Library | visceral AND (pain OR hyperalgesia OR algesia) AND (acupuncture OR electroacupuncture OR acupoint) |
Search results were screened based on the titles and abstracts before full text assessments. We included original studies that investigated the therapeutic effects and/or the mechanisms of acupuncture on visceral pain. Both animal and human studies written in English or Chinese were included. In this review, we considered manual acupuncture (MA), electroacupuncture (EA), transcutaneous electrical nerve stimulation on acupoints (acu-TENS), pharmacopuncture (injection of herbal medicine into acupoints, e.g., sweet bee venom), and laser acupuncture (LA) techniques as the different types of acupuncture.
Concerning the studies on human subjects, we evaluated the risk of bias associated with each of them using either the revised Cochrane risk of bias tool for randomized trials (RoB 2.0 [
Our search strategy resulted in the retrieval of 192 articles in total. Following this, in addition to removing the duplicates (n=35), 111 studies were excluded based on their titles and abstracts. Among the excluded studies, 67 studies were unrelated to visceral pain or acupuncture, 28 studies were not original, and 11 studies were written in languages other than English or Chinese. Further, full texts corresponding to four studies, each published before 1990, could not be obtained, and one study was retracted. Ultimately, 46 articles were included in this review (Figure
Flow diagram of article inclusion.
There were seven studies with human subjects. Two studies included irritable bowel syndrome (IBS) patients [
Overview of visceral pain studies on humans.
Author | Participants group:n(f)/ | Acupuncture groups | Control groups | Outcomes | Results | ||
---|---|---|---|---|---|---|---|
Acupuncture | acupoints | Control | acupoints | ||||
(1) Thomas et al. (1995) [ | Primary dysmenorrhea | (a) MA | (a), (b), (c), (d): BL32, CV4, SP6, 9 | (g) Sham TENS (ns) | Spinous processes Thoracic 10-Lumbar 1 | (1) Blood loss | Within group |
(2) Kotani et al. (2001) [ | (1) Upper abdominal surgery | (A) Patient 1 +MA | (A) BL18, 19, 20, 21, 22, 23, 24 | (C) Patient 1+sham MA (ni) | (C) BL18, 19, 20, 21, 22, 23, 24 | (1) Incisional, visceral pain | Within group |
(3) Xing et al. (2004) [ | IBS | (a) acu-TENS (5Hz, 250ms) | (a) ST36, PC6 | (b) TENS (5Hz, 250ms) | (b) non-acupoint | (1) Rectal tone | Within group |
(4) Chu et al. (2012) [ | IBS | (A) EA (10Hz, 0.5ms, 60v) | (A) ST36, 37, SP6 | (B) Sham EA (ns) | (B) ST36, 37, SP6 | (1) fMRI-rectal distention | Within group |
(5) Leung et al. (2013) [ | Healthy | (A) acu-TENS (2Hz, 0.2ms) | (A) LI4, PC6, ST36 | (B) Sham TENS (ns) | (B) LI4, PC6, ST36 | (1) Tolerance to rectal sensation | Between groups |
(6) Juel et al. (2016) [ | Healthy | (a) MA | (a) CV4, 6, 7, 9, 10, 12, ST25, 26, 37, LI4 +non-acupoints | (b) Sham MA (ni) | (b) ST37, LI4 | (1) Rectal distention volume | Within groups |
(7) Juel et al. (2017) [ | Chronic pancreatitis | (a) MA | (a) CV4, 6, 9, 10, 12, ST25, ST36, SP6, 8, 9, 15+non-acupoints | (b) Sham MA (ni) | (b) CV4, 6, 9, 10, 12, ST25, ST36, SP6, 8, 9, 15+non-acupoints | (1) Reduced pain score | Between groups |
Group written in lowercase letters (e.g., (a), (b), and (c)): different treatments in the same population, unless stated otherwise; Group written in capital letters (e.g., (A), (B), and (C)): different treatments in different population
Acu: acupuncture group; ACC: anterior cingulate cortex; BL: Bladder Meridian; Con: control group; CV: Conception Vessel Meridian; EA: electro-acupuncture; EEG: electroencephalography; f: female; fMRI: functional magnetic resonance imaging; IBS: irritable bowel syndrome; INS: insula; LI: Large Intestine Meridian; MA: manual acupuncture; n: number; ni: not inserted; ns: not stimulated; PC: Pericardium Meridian; PFC: prefrontal cortex; pgCC: perigenual cingulate cortex; SC: somatosensory cortex; SP: Spleen Meridian; ST: Stomach Meridian; Temp: temporal lobes; TH: thalamus; (acu-)TENS: Transcutaneous electrical nerve stimulation (on acupoints); min: minutes; ms: milliseconds; v: volts.
Among the seven studies conducted on humans, the various types of acupuncture techniques that were used are as follows: MA in four studies [
Frequency distribution of acupuncture points in the human and animal studies on visceral pain. Acupuncture points on Stomach Meridian (ST) and Conception Vessel Meridian (CV) are most frequently selected for visceral pain. Aur: auricular acupoints, Lumb: lumbar acupuncture points, n: number of studies reporting the acupuncture points, BL: Bladder Meridian, GB: Gallbladder Meridian, LI: Large Intestine Meridian, LR: Liver Meridian, PC: Pericardium Meridian, SP: Spleen Meridian, and TE: Triple Energizer Meridian.
Schematic illustration of functional and metabolic changes (peptides, proteins, and mRNA) of the brain-gut axis by acupuncture in visceral pain studies. In human, acupuncture consistently enhanced the functional activity in the thalamus and insula, the core brain regions of pain processing. In animal, a great variety of metabolic changes have been reported as well as functional neural activities, demonstrating that acupuncture induces a wide range of changes through the brain-gut axis in visceral pain. ACC: anterior cingulate cortex; AMG: amygdala; CC: central canal; DH: dorsal horn; DRG: dorsal root ganglion; DRN: dorsal raphe nucleus; HyTH: hypothalamus; INS: insula; MED: medulla; NR2B: N-methyl-D-aspartate receptor subunit; PAG: periaqueductal gray; PFC: prefrontal cortex; P2X3: P2X purinoceptor 3; SC: somatosensory cortex; sub P: substance P; TH: thalamus; 4th V: fourth ventricle.
There were three randomized parallel-group trials [
Out of the seven studies, three studies were classified as having low overall risks of bias. Further, two randomized studies [
We found 39 studies that examined various visceral pain models in animals. Thirty-one studies used rats [
Visceral hypersensitivity models in animal studies (visceral hypersensitivity and CRD models).
Author | Model | Acupuncture groups | Control groups | Outcomes | Results | ||
---|---|---|---|---|---|---|---|
Acupuncture | acupoints | Control | acupoints | ||||
(1) Cui et al. | Visceral hypersensitivity+CRD (SD rat, m, various) | (A) Model+EA (4/100Hz, 1mA) | (A) ST36, 37 | (B) Control | (A) ST36, 37 | (1) AWR | Between groups |
(2) Tian et al. | (1) Colorectal irritation-induced visceral hypersensitivity (SD rat, m, 6/group) | (A) Model 1+EA (2Hz, 0.3mA) | (A), (B) ST36, SP6 | (C) Control | - | (1) AWR | Between groups |
(3) Liu et al. | Visceral hypersensitivity | (A) Model+EA (2/100Hz, 0.2–0.6ms, 1mA) | (A) ST25, ST37 | (B) Control | - | (1) AWR | Between groups |
(4) Xu et al. | Visceral hypersensitivity +CRD (SD rat, m, 6-25/group total 74) | (A) Model+EA (2/100Hz, 0.1ms, 1mA) | (A), (B) ST36 | (C) Control | (E), (F) ST36 | (1) VMR | Within group |
(5) Wu et al. | Visceral hypersensitivity +CRD (SD rat, m, 8/group) | (A) Model+EA (10Hz, 0.18ms, ~3mA) | (A) ST36 | (B) Control | (B) ST36 | (1) Pain threshold to CRD | Between groups |
(6) Qi et al. | Visceral hypersensitivity +CRD (SD rat, m, 8/group) | (A) Model+EA (5/100Hz) | (A) ST36, 37 | (B) Control | (D) ST36, 37 | (1) Pain threshold pressure | Within group |
(7) Qi et al. | Visceral hypersensitivity +CRD (SD rat, m, 8/group) | (A) Model+EA (5/100Hz) | (A) ST36, 37 | (B) Control | (D) ST36, 37 | (1) AWR | Between groups (1), (2) |
(8) Zhou et al. | Stress-induced visceral hypersensitivity (SD rat, m, 5-8/group total 94) | (A) Model+EA (2/100Hz, 0.1ms, 1mA) | (A) ST36 | (B) Model | (C)-(E), (H)-(J) ST36 | (1) VMR | Within group |
(9) Weng et al. | Visceral hypersensitivity +CRD (SD rat, m, 8/group) | (A) Model+EA (2/100Hz, 2mA) | (A) ST25, 37 | (B) Control | - | (1) AWR | Between groups |
(10) Qi et al. | Visceral hypersensitivity+CRD (SD rat, m, various/group total 184) | (A) Model+EA (2Hz, 1-3mA) | (A)-(F) ST36, 37 | (D) Model+EA (2Hz, 1-3mA)+NAL | (D)-(G) ST36, 37 | (1) AWR | Within group |
(11) Liu et al. | Visceral hypersensitivity (SD rat, m, 8/group) | (A) Model+EA (5/25Hz, 1mA) | (A) ST36, 37 | (B) Control | (C) ST36, 37 | (1) AWR | Between groups |
(12) Zhou et al. | Visceral hypersensitivity +restraint stress (SD rat, m, 16/8) | (a), (b) Model+EA (100Hz, 1mA) | (a), (b) ST36 | (C) Control | (d) ST36 | (1) Activity of acromiotrapezius | Within group |
Group written in lowercase letters (e.g., (a), (b), and (c)): different treatments in the same population, unless stated otherwise. Group written in capital letters (e.g., (A), (B), and (C)): different treatments in different population.
ACC: anterior cingulate cortex; AWR: abdominal withdrawal reflex; BL: Bladder Meridian; CRD: colorectal distention; DRG: dorsal root ganglion; EA: electro-acupuncture; ECG: Electrocardiography; f: female; HF: high frequency heart rate variability; LF: low frequency heart rate variability; m:male; mA: milliampere; min: minutes; ms: milliseconds; NR2B: N-methyl-D-aspartate receptor subunit NR2B; NAL: naloxone; ns: not stimulated; PFC: prefrontal cortex; RVM: rostral ventromedia medulla; SAL: saline; SD: Sprague Dawley; ST: Stomach Meridian; VMR: visceral motor response (reflex); 5-HT: 5-hydroxytryptamine (serotonin).
Visceral hypersensitivity models in animal studies (other models).
Author | Model | Acupuncture groups | Control groups | Outcomes | Results | ||
---|---|---|---|---|---|---|---|
Acupuncture | Acupoints | Control | Acupoints | ||||
(1) Du et al. (1976) [ | Splanchnic nerve stimulation (cat, -,-) | (A) Model+EA (25/70/100Hz) | (A) GB31, 34, LI11, TE5 | - | - | (1) VSR | Within group |
(2) Zhang et al. (1989) [ | Splanchnic nerve stimulation (cat, -, total 35) | (A) Model+EA (5Hz) | (A) PC6 | (B) Model+Morphine | (C) PC6 | (1) C-CEPs | Within group |
(3) Guoxi (1991) [ | Splanchnic nerve stimulation (cat, m, total 219) | (A) Model+EA | (A) ST36 | - | - | (1) Electrical activities in thalamus | Within group |
(4) Shu et al. (1994) [ | Splanchnic nerve stimulation (Wistar rat, m, 3/4/4) | (A) Model+EA | (A) ST36, SP6 | (B) Control | - | (1) Pain threshold | Within group |
(5) Cai et al. (1994) [ | Splanchnic nerve stimulation (rabbit, m/f, 8/4/6/6/7/9/6/6) | (A) Model+EA (25Hz)+SAL | (A) EX-B2 (T12,L1,L2) | (B) Model+SAL | (D)-(H) EX-B2 | (1) Pain threshold | Within group |
(6) Kwon et al. (2001) [ | Acetic acid injection (ICR mice, m, 10-20/group) | (A) Model+BV | (A) CV12 | (D) Model+BV | (D) non-acupoint | (1) Abdominal stretches | Between groups |
(7) Yu et al. | Acetic acid injection (mice, m/f, 12/group) | (A) WT Model+MA | (A),(B) CV12, ST36 | (C) WT control | - | (1) c-Fos in the spinal dorsal horn | Between groups |
(8) Yu et al. | Acetic acid injection (mice, m/f, 18/group) | (A) Model+WT MA | (A),(B) CV12, ST36 | (C) WT control | - | (1) Latency of writhing response | Between groups |
(9) Liu et al. (2010) [ | Acetic acid injection (SD rat, m/f, 6/group) | (A) Model+EA (2/20Hz) | (A)-(C) ST2 | (D) Control | (F) ST2 | (1) Abdominal muscular contractions | Between groups |
(10) Liu et al. (2011) [ | Acetic acid injection (SD rat, -, -) | (A) Model+EA (2/20Hz, 1.0mA) | (A)-(E) ST2 | (H) Control | (J) ST2 | (1) c-Fos | Within group |
(11) Gong et al. | Antimonium potassium tartrate injection (Wistar rat, m/f, 15/10/7/-/12/8/9/8/6/6/10/8/15/15) | (A) Model+EA (45/12.5Hz) | GV26, CV24 | (C) Control | (E)-(N) GV26, CV24 | (1) Writhing response | Between groups |
(12) Xu et al. (2010) [ | Formalin injection (SD rat, m, 8/group) | (A) EA (20Hz, ~1mA) | (A), (B) EX-B2 (L3, 6) | (C) Control | - | (1) Visceral pain behavior | Between groups |
(13) Rong et al. | CRD (SD rat, m, total 67) | (A) Model+non receptive field MA (2-3Hz) | (A) ST36 (contr) | (C) Model | (G) ST36 (contralateral) | (1) Electrical activities of spinal dorsal horn WDR neurons of L1-L3 | Within groups |
(14) Rong et al. | CRD (SD rat, -, 17/17/9/15/9) | (A), (B) Model+MA (2Hz) | (A) ST36 (contr) | (C) Pinch (contr) | - | (1) Electrical activities in spinal dorsal horn | Between groups |
(15) Zhang et al. (2009) [ | CRD (SD rat, m, 58) | (a), (b) Model+EA (2Hz, 1mA) | (a) ST36 (contr) | (c) Model | (c)-(e) center of receptive field | (1) Electrical activities in thalamus | Between groups |
(16) Chen et al. (2010) [ | CRD (Wistar rat, m, 9/group) | (A) Model+EA | (A) ST36 | (D) Control | (E) non-acupoint | (1) MAP | Within group |
(17) Liu et al. (2014) [ | CRD (SD rat, m, 62) | (a)-(c) Model+EA (10Hz, 2mA) | (a) ST36 | - | - | (1) Electrical activities in NTS | Within group |
(18) Yu et al. (2014) [ | CRD (SD rat, m, 10-11/group) | (a) Model+EA (15Hz, 1.5mA) | (a)-(c) ST36, 37 | (d) Model | - | (1) Electrical activities of wide dynamic range neurons | Within group |
(19) Li et al. (2014) [ | CRD (SD rat, f, 8/7/7/7) | (A) Model+auricular EA (25Hz, 0.8mA) | (A) Auricular acupoints (stomach, small intestine) | (B) Control | (D) no vagal innervation points | (1) VMR | Within group |
(20) Yu et al. (2014) [ | CRD (SD rat, m, 22) | (a) preEA+Model+EA (15Hz, 1mA) | (a)-(d) ST36 (ips) | - | - | (1) Electrical activities of WDR in lumbar spinal cord | Within group |
(21) Liu et al. (2015) [ | CRD (SD rat, m, 8/group) | (A) Model+EA (2/100Hz) | (A) ST37 | (B) Control | (D) ST37 | (1) AWR | Between groups |
(22) Rong et al. (2015) [ | CRD (SD rat, m, 26) | (a) Model+EA (20Hz) | (A) ST36, 37 | (b) Model | - | (1) Discharge frequency of VPL neurons in thalamus | Within group |
(23) Iwa et al. | Rectal distension (Dog, f 4, 6/group) | (A) Model+EA (10Hz) | (A) ST36 | (B) Model+EA | (B) BL21 | (1) Arterial | Within group |
(24) Lin et al. (2009) [ | Gastric distension (SD rat, m, 10/group) | (A) Model+EA (2Hz, 1-3mA) | (A),(B) ST36 | (C) Control | - | (1) Pain score | Within group |
(25) Sun et al. (1991) [ | Somatic and visceral noxious stimuli (Wistar rat, m/f, 23/28/-/16) | (A) Model+EA (6v, 8Hz) | (A) ST36 | (B) Model | - | (1) Discharge of PEN in VPN | Within group |
(26) Lorenzini et al. (2010) [ | Cystitis (SD rat, m, total 48) | (A) Cystitis+PWL | (A)-(F) ST36, TE5 | (B) Cystitis | - | (1) Urinary bladder weight, mucosal erosion, ulceration, edema, petechial hemorrhages, thickness of bladder wall | Within group |
(27) Yang et al. (2010) [ | Visceral traction (SD rat, m, 10/group) | (A) Model+ LA (650nm, 10mW) | (A) ST36 | (B) Sham model | (D) ST36 | (1) Pain score | Between groups |
Group written in lowercase letters (e.g., (a), (b), and (c)): different treatments in the same population, unless stated otherwise. Group written in capital letters (e.g., (A), (B), and (C)): different treatments in different population.
ACC: anterior cingulate cortex; A-CEPs: cortical evoked potentials of A-fibers; AChE: acetylcholinesterase; APO: apomorphine; AWR: Abdominal withdrawal reflex; BL: Bladder Meridian; BV: bee venom; C-CEPs: cortical evoked potentials of C-fibers; CCGM: centralis corpus geniculatum medialis; contr: contralateral; CP: caudate putamen; CPTN: caudal spinal trigeminal nucleus; CRD: colorectal distension; CRH: corticotropin-releasing hormone; CSF: cerebrospinal fluid; CV: Conception Vessel Meridian; DA: dopamine; DMN: dorsal motor nucleus; DOPAC: dopaceticacid; EA: electro-acupuncture; f: female; GB: Gall Bladder Meridian; GFAP: glial fibrillary acidic protein; GV: Governing Vessel Meridian; HA: hypothalamic arcuatus; HF: high frequency heart rate variability; Hippo: hippocampus; HL: habenulae lateralis; HR: heart rate; HRV: heart rate variability; HT: heterozygote; HVA: homovanillic acid; ION: infraorbital nerve; ips: ipsilateral; IT: intrathecal injection; L: lumbar vertebrae; LA: laser acupuncture; LC: locus coeruleus; LDH: lumbar dorsal horns; LEK: leu-enkephalin; LF: low frequency heart rate variability; LI: Large Intestine Meridian; LR: Liver Meridian; m:male; MA: manual acupuncture; mA: milliampere; MAP: mean arterial pressure; MCP: metoclopramide; min: minutes; Moxa: moxibustion; mRNA: messenger ribonucleic acid; ms: milliseconds; NAL: naloxone; NCS: nucleus centralis superior; NRD: nucleus raphe dorsalis; NRG: nucleus reticular gigantocellularis; NRM: nucleus raphe magnus; ns: not stimulated; NSL: nucleus septal lateralis; NTS: nucleus tractus solitarii; PAG: periaqueductal gray; PC: Pericardium Meridian; CPC: centromedian-parafascicula; PEN: pain-excitation neurons; PGE2: prostaglandin E2; PGL: paragigantocellularis lateralis, PIN: pain-inhibitory neurons; PTN: paratrigeminal nucleus; PVN: paraventricular nucleus; PWL: pulsed wave laser; RF: reticular formation; SAL: saline; s: seconds; SC: somatosensory cortex; SD: Sprague Dawley; SP: substance P; SRD: subnucleus reticularis dorsalis; ST: Stomach Meridian; T: thoracic vertebrae; TDH: thoracic dorsal horns; TE: Triple Energizer Meridian; TPV: thalamic posterior ventralis; VMR: visceral motor response (reflex); VPL: ventralis posterior lateralis; VPN: ventral posterolateral nucleus; VSR: viscerosomatic reflex discharges; WDR: wide dynamic range; WT: wild type; Yo: yohimbine; 5-HT: 5-hydroxytryptamine receptor.
Summary of significant results from the included studies.
Outcomes | Within acupuncture group | vs. sham acupuncture group | vs. no treatment group | |
---|---|---|---|---|
Behavioral | Human | Intake of analgesics ↓ [ | Analgesic effect ↑ [ | |
Animal | Pain score ↓ Pain threshold ↑ [ | Pain threshold ↑ [ | Pain score/behavior ↓ [ | |
Abdominal withdrawal reflex ↓ [ | Abdominal withdrawal reflex ↓ [ | Abdominal withdrawal reflex ↓ [ | ||
Abdominal muscle activity ↓ [ | Abdominal muscle activity ↓ [ | Abdominal muscle activity ↓ [ | ||
Writhing response ↓ [ | Writhing response ↓ [ | |||
| ||||
Metabolic | Human | |||
Animal | ||||
| ||||
Gut | Animal | c-Fos ↓ [ | Serotonin ↓ 5-HT4 receptor ↑ [ | |
| ||||
Spinal cord | Animal | Neural activity in wide dynamic range neurons ↑ [ | Serotonin and c-Fos in superficial dorsal horn ↓ [ | Metabolic rate of glucose in thoracic dorsal horns ↓/lumbar dorsal horns ↑ [ |
| ||||
Brain/brain stem | Human | Perigenual cingulate/prefrontal cortex, temporal lobes, insula, somatosensory cortex ↑ [ | Thalamus, insula ↑ [ | |
Animal | Neural activity in subnucleus reticularis dorsalis ↑ [ | Neuronal response to colorectal distention in thalamus ↑ [ | Glucose metabolic rate in ventral periaqueductal gray, nucleus centralis superior ↓/ periaqueductal gray, gigantocellular reticular nucleus ↑ [ |
AChE: acetylcholinesterase; CRH: corticotropin-releasing hormone; NMDA: N-methyl-D-aspartate; NR2B: N-methyl-D-aspartate receptor subunit NR2B; 5-HT: 5-hydroxytryptamine receptor; P2X3: P2X purinoceptor 3.
Further, concerning the animal studies, EA was the intervention that was used in most of them [
To our knowledge, this is the first study to systematically review the mechanisms behind the effects of acupuncture on visceral pain studied in both humans and animals through the brain-gut axis. In the 46 included studies in our review, significant improvements in pain-related behaviors were consistently reported in both humans and animals included in the acupuncture treatment groups compared to those included in the sham acupuncture or no-treatment groups. Increased secretion of
Pain commonly causes hyperactivity of the hypothalamic-pituitary-adrenal system resulting in elevated plasma hormone levels such as those of cortisol, epinephrine, and adrenocorticotropin [
Since visceral pain originates in the gastrointestinal tract and its peripheral regions, changes in the immune and nervous systems and changes in the microbial environment of the gut have been investigated.
The spinal cord is the first region in which incoming pain signals are transmitted to the central nerves. The spinal cord receives sensory information from the whole body and transmits this information to several regions of the brain that are responsible for processing pain [
A set of brain regions, collectively called the “visceral pain network,” are the core of the perception and modulation of internal and external stimuli in the gut [
We only assessed the quality of the human studies and found that only three studies were classified as having low overall risks of bias while two studies were considered as having high risks of bias. A few assessment tools have been developed for assessing the quality of animal studies, but they are not widely accepted nor validated in the field yet. Moreover, since most of the animal studies included in our review did not report on having employed ways to minimize the risk of bias, such as the blinding of the outcome assessor or randomization methods, we could only assume that they were at high risks of bias.
It is also important to assess the reporting quality of the acupuncture interventions. There are well-known guidelines, the STRICTA guidelines (STandards for Reporting Interventions in Clinical Trials of Acupuncture [
Based on these results, we found that acupuncture induces analgesic effects on visceral pain via multiple pathways from the peripheral organs (gut) to the CNS (brain). Visceral organs are where visceral pain occurs, and acupuncture directly regulates visceral pain by reducing the levels of intrinsic inflammatory biomarkers and increasing the levels of serotonin and endogenous opioid neurotransmitters. The neural signals induced by acupuncture are also transmitted to the brain through the spinal cord, and it attenuates the peripheral neural activity and concentrations of the inflammatory-biomarkers such as p38, P2X3, and NR2B in the spinal cord. In the brain, acupuncture attenuates the levels of neural activity and pain excitation neurons in the thalamus and reduces stress-related hormone levels in the hypothalamus, which suggests that the neural and hormonal changes in the thalamus and hypothalamus are involved in the pain modulatory effects of acupuncture on visceral pain. Moreover, acupuncture induces an increase in the levels of
With this review, we were able to present the broad outline of the acupuncture signal-transduction system from the gut to the CNS, but the acupuncture signaling pathways from the spinal cord to the intestine or the gut-brain signal-transduction system are still unclear. Further experimental studies are needed to elucidate the entire signaling mechanism of acupuncture from the peripheral to the central organs.
This review summarizes the findings from previous studies associated with the neural and chemical changes that take place through the brain-gut axis in both humans and animals in order to reveal the underlying mechanisms behind the effects of acupuncture treatment on visceral pain. The results of this review demonstrated significant improvements in visceral pain following acupuncture treatments. However, achieving an integrative understanding of the mechanism of acupuncture on visceral pain remains a long-term endeavor. High heterogeneity among the included studies (various visceral pain conditions and models along with diverse outcome measures and heterogeneous results) and the lack of detailed descriptions outlining the treatment methods also raise concerns.
In future studies, the thalamus and the brain-gut axis could be considered as targets or markers of the visceral pain that is modulated by acupuncture. Furthermore, studies on changes in the levels of neurotransmitters or neuropeptides in the gut and the brain may improve our knowledge of visceral pain modulation by acupuncture treatment.
The authors declared no conflicts of interest.
This review was conceived and designed by Ji-Yeun Park and In-Seon Lee. Ji-Yeun Park and In-Seon Lee developed the search strategy, and In-Seon Lee conducted the database search. Ji-Yeun Park, In-Seon Lee, and Soyeon Cheon assessed studies for inclusion and extracted and analyzed the data. Ji-Yeun Park, In-Seon Lee, and Soyeon Cheon prepared the manuscript draft. All the authors approved the final version of the manuscript for publication. In-Seon Lee is currently supported by the Intramural Research Program of the National Center for Complementary and Integrative Health, National Institutes of Health.
This work was supported only by the Daejeon University Research Grants (2016).
Two supplementary tables reporting the risk of bias of included clinical studies regarding the quality of the included studies. We assessed the risk of bias with RoB 2.0 tool for randomized controlled trials (n=6, supplementary Table 1) and ROBINS-I tool for non-randomized clinical trial (n=1, supplementary Table 2).