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1.
Int J Mol Sci ; 24(19)2023 Oct 02.
Article in English | MEDLINE | ID: mdl-37834289

ABSTRACT

The management of abdominal pain in patients affected by inflammatory bowel diseases (IBDs) still represents a problem because of the lack of effective treatments. Acetyl L-carnitine (ALCAR) has proved useful in the treatment of different types of chronic pain with excellent tolerability. The present work aimed at evaluating the anti-hyperalgesic efficacy of ALCAR in a model of persistent visceral pain associated with colitis induced by 2,4-dinitrobenzene sulfonic acid (DNBS) injection. Two different protocols were applied. In the preventive protocol, ALCAR was administered daily starting 14 days to 24 h before the delivery of DNBS. In the interventive protocol, ALCAR was daily administered starting the same day of DNBS injection, and the treatment was continued for 14 days. In both cases, ALCAR significantly reduced the establishment of visceral hyperalgesia in DNBS-treated animals, though the interventive protocol showed a greater efficacy than the preventive one. The interventive protocol partially reduced colon damage in rats, counteracting enteric glia and spinal astrocyte activation resulting from colitis, as analyzed by immunofluorescence. On the other hand, the preventive protocol effectively protected enteric neurons from the inflammatory insult. These findings suggest the putative usefulness of ALCAR as a food supplement for patients suffering from IBDs.


Subject(s)
Colitis , Visceral Pain , Humans , Rats , Animals , Acetylcarnitine/pharmacology , Acetylcarnitine/therapeutic use , Visceral Pain/drug therapy , Visceral Pain/etiology , Hyperalgesia/drug therapy , Hyperalgesia/etiology , Colitis/chemically induced , Colitis/complications , Colitis/drug therapy , Neuroglia , Central Nervous System
2.
Oxid Med Cell Longev ; 2023: 4463063, 2023.
Article in English | MEDLINE | ID: mdl-36713031

ABSTRACT

Visceral pain caused by inflammatory bowel disease (IBD) greatly diminishes the quality of life in affected patients. Yet, the mechanism of how IBD causes visceral pain is currently not fully understood. Previous studies have suggested that the central nervous system (CNS) and gut-brain axis (GBA) play an important role in IBD-inducing visceral pain. As one of the treatments for IBD, electroacupuncture (EA) has been used to treat various types of pain and gastrointestinal diseases in clinical practice. However, whether EA relieves the visceral pain of IBD through the gut-brain axis has not been confirmed. To verify the relationship between visceral pain and CNS, the following experiments were conducted. 1H-NMR analysis was performed on the prefrontal cortex (PFC) tissue obtained from IBD rat models to determine the link between the metabolites and their role in EA treatment against visceral pain. Western blot assay was employed for detecting the contents of glutamate transporter excitatory amino acid transporters 2 (EAAT2) and the glutamate receptor N-methyl-D-aspartate (NMDA) to verify whether EA treatment can alleviate neurotoxic symptoms induced by abnormal increases of glutamate. Study results showed that the glutamate content was significantly increased in the PFC of TNBS-induced IBD rats. This change was reversed after EA treatment. This process was associated with increased EAAT2 expression and decreased expression of NMDA receptors in the PFC. In addition, an increase in intestinal glutamic-metabolizing bacteria was observed. In conclusion, this study suggests that EA treatment can relieve visceral pain by reducing glutamine toxicity in the PFC, and serves an alternative clinical utility.


Subject(s)
Electroacupuncture , Inflammatory Bowel Diseases , Visceral Pain , Rats , Animals , Rats, Sprague-Dawley , Visceral Pain/therapy , Visceral Pain/etiology , Visceral Pain/metabolism , Electroacupuncture/methods , Trinitrobenzenesulfonic Acid , Quality of Life , Inflammatory Bowel Diseases/complications , Prefrontal Cortex/metabolism , Glutamates
3.
J Ethnopharmacol ; 264: 113352, 2021 Jan 10.
Article in English | MEDLINE | ID: mdl-32891821

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Irritable bowel syndrome (IBS) is a chronic, stress-related, functional gastrointestinal disorder characterized by abdominal discomfort and altered bowel habits; the manipulation of the microbiota is emerging as a promising therapeutic option for IBS. Cynanchum thesioides (CT) is an herb of traditional Mongolian medicine that has been employed in treating abdominal pain and diarrhea for hundreds of years. Phytochemical studies of this plant showed the presence of various flavonoids with antibacterial and anti-inflammatory activities. We hypothesized that Cynanchum thesioides manipulates the gut mycobiome and reverses visceral hypersensitivity in IBS rat model. PURPOSE OF THE STUDY: The aims of this study were to prove the in vivo efficacy of Cynanchum thesioides on improving visceral hypersensitivity in IBS rat model and to examine its effect on gut bacterial communities, focusing on the potential interrelationships among microbiota and visceral hypersensitivity. MATERIALS AND METHODS: We induced visceral hypersensitivity rat models by maternal separation (MS) of Sprague-Dawley rats, and administered CT water extracts to MS rats for 10 consecutive days. The abdominal withdrawal reflex score and threshold of colorectal distention were employed to assess visceral sensitivity. We then used the Illumina HiSeq platform to analyze bacterial 16S rRNA gene. RESULTS: Treatment with CT improved visceral hypersensitivity in MS rats, and this was accompanied by alterations in the structure and composition of the gut microbiota. The extent of the stability of the gut microbiota was improved after treatment with CT. The genera Pseudomonas, Lachnospiracea_incertae_sedis, and Clostridium XlVa (which were more prevalent in MS rats) were significantly decreased, whereas the abundance of some genera were less prevalent in MS rats-for example, Clostridium IV, Elusimicrobium, Clostridium_sensu_stricto, and Acetatifactor were significantly enriched after treatment with CT. CONCLUSION: Water-extracted CT was beneficial against visceral hypersensitivity in IBS and favorably affected the structure, composition, and functionality of gut microbiota. CT is therefore a promising agent in therapy of IBS.


Subject(s)
Cynanchum , Gastrointestinal Microbiome/drug effects , Irritable Bowel Syndrome/diet therapy , Maternal Deprivation , Plant Extracts/therapeutic use , Visceral Pain/drug therapy , Animals , Animals, Newborn , Gastrointestinal Microbiome/physiology , Irritable Bowel Syndrome/etiology , Irritable Bowel Syndrome/psychology , Male , Plant Extracts/isolation & purification , Random Allocation , Rats , Rats, Sprague-Dawley , Visceral Pain/etiology , Visceral Pain/psychology , Water
4.
Int J Mol Sci ; 21(12)2020 Jun 17.
Article in English | MEDLINE | ID: mdl-32560291

ABSTRACT

The management of chronic visceral pain related to Inflammatory Bowel Diseases or Irritable Bowel Syndrome is still a clinical problem and new therapeutic strategies continue to be investigated. In the present study, the efficacy of a pomegranate decoction and of its polysaccharide and ellagitannin components in preventing the development of colitis-induced abdominal pain in rats was evaluated. After colitis induction by 2,4-dinitrobenzenesulfonic acid (DNBS), the pomegranate decoction (300 mg kg-1), polysaccharides (300 mg kg-1), and ellagitannins (45 mg kg-1) were orally administered for 14 days. Repeated treatment with decoction reduced visceral hypersensitivity in the colitic animals both at 7 and 14 days. Similar efficacy was shown by polysaccharides, but with lower potency. Ellagitannins administered at dose equivalent to decoction content showed higher efficacy in reducing the development of visceral pain. Macroscopic and microscopic evaluations performed on the colon 14 days after the damage showed that all three preparations reduced the overall amount of mast cells, the number of degranulated mast cells, and the density of collagen fibers in the mucosal stroma. Although ellagitannins seem to be responsible for most of the beneficial effects of pomegranate on DNBS-induced colitis, the polysaccharides support and enhance its effect. Therefore, pomegranate mesocarp preparations could represent a complementary approach to conventional therapies for promoting abdominal pain relief.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Colitis/complications , Plant Extracts/pharmacology , Pomegranate/chemistry , Visceral Pain/etiology , Animals , Anti-Inflammatory Agents/chemistry , Biomarkers , Disease Models, Animal , Immunohistochemistry , Plant Extracts/chemistry , Rats , Retreatment , Treatment Outcome , Visceral Pain/diagnosis , Visceral Pain/drug therapy
5.
Arq. bras. neurocir ; 38(4): 272-278, 15/12/2019.
Article in English | LILACS | ID: biblio-1362490

ABSTRACT

Cardiovascular disease (CVD) is the main cause of death worldwide, including in Brazil. Angina pectoris is a challenging disease because its clinical manifestation is not always related to the degree of obstruction. Visceral pain fromany source can be totally disabling. It influences all aspects of the life of a patient and it can be one of the main causes of absence from work and of family disruption. Spinal cord electrical stimulation (SCES) has been traditionally applied for the treatment of neuropathic pain, with good to excellent results. Visceral pain syndrome can be as debilitating and disabling as somatic or neuropathic pain; however, there seems to be a lack of consensus on the appropriate treatment and strategies for these disorders. Themajor difference of SCES for visceral pain, compared to postlaminectomy syndrome or to regional complex syndrome, is the number of stimulated dermatomes. In most viscera, the somatotopic arrangement has two to four medullar levels, sometimes requiring laterality. After reviewing the literature, we have concluded that SCES is now a viable, low-risk option with satisfactory results for the treatment of neuropathic and visceral pain; therefore, it can be used in refractory angina after the failure of standard therapy. However, further studies are required to increase the application and efficacy of this procedure in the clinical practice.


Subject(s)
Humans , Male , Middle Aged , Spinal Cord , Transcutaneous Electric Nerve Stimulation/methods , Visceral Pain/therapy , Angina Pectoris/therapy , Treatment Outcome , Visceral Pain/etiology , Angina Pectoris/diagnostic imaging
6.
Neurogastroenterol Motil ; 31(12): e13710, 2019 12.
Article in English | MEDLINE | ID: mdl-31429514

ABSTRACT

BACKGROUND: Different physical exercise interventions for pain and other related symptoms largely follow non-personalized guidelines and show a high degree of variability in outcome. These interventions are considered to have different pathways toward improvement in autonomic regulation of energy metabolism. The current pilot study was conducted to assess the predictive value of individual cardiovascular (CV) activity markers at rest to predict clinical outcomes for two popular exercise-based interventions (walking and yoga) in patients with Irritable Bowel Syndrome (IBS). METHODS: Twenty-seven adult participants with IBS were randomly assigned to a 16-biweekly Iyengar yoga or walking program. They completed pre- and post-treatment assessments on IBS symptom severity, affective and somatic complaints, and various measures of resting autonomic function including blood pressure (BP), heart rate and its variability, baroreceptor sensitivity (BRS) to activations and inhibitions with gains of brady- and tachycardiac baro-responses, and BP start points for these spontaneous baroreflexes. RESULTS: Pretreatment BRS was differentially related to clinical response for the treatment groups. Specifically, a significant decrease in pain severity was found in response to yoga for those participants who had lower resting BRS to activations, but decreased pain severity was associated with higher resting BRS for those in the walking group. The effect was not related to affective symptom relief. Other CV measures showed similar associations with clinical outcomes for both groups. CONCLUSIONS: The data suggest therefore that CV based phenotypes may be useful in personalizing clinical interventions for IBS. They may also point to autonomic mechanisms that are targets for such interventions.


Subject(s)
Abdominal Pain/therapy , Chronic Pain/therapy , Exercise Therapy/methods , Heart Rate/physiology , Irritable Bowel Syndrome/complications , Precision Medicine/methods , Walking , Yoga , Abdominal Pain/etiology , Adolescent , Adult , Aged , Baroreflex , Chronic Pain/etiology , Female , Humans , Irritable Bowel Syndrome/psychology , Life Style , Male , Middle Aged , Pain Management , Phenotype , Pilot Projects , Pressoreceptors/physiopathology , Rest/physiology , Socioeconomic Factors , Treatment Outcome , Visceral Pain/etiology , Visceral Pain/therapy , Walking/physiology , Young Adult
7.
Biochem Pharmacol ; 157: 134-147, 2018 11.
Article in English | MEDLINE | ID: mdl-30076849

ABSTRACT

Cannabis sp. and their products (marijuana, hashish…), in addition to their recreational, industrial and other uses, have a long history for their use as a remedy for symptoms related with gastrointestinal diseases. After many reports suggesting these beneficial effects, it was not surprising to discover that the gastrointestinal tract expresses endogenous cannabinoids, their receptors, and enzymes for their synthesis and degradation, comprising the so-called endocannabinoid system. This system participates in the control of tissue homeostasis and important intestinal functions like motor and sensory activity, nausea, emesis, the maintenance of the epithelial barrier integrity, and the correct cellular microenvironment. Thus, different cannabinoid-related pharmacological agents may be useful to treat the main digestive pathologies. To name a few examples, in irritable bowel syndrome they may normalize dysmotility and reduce pain, in inflammatory bowel disease they may decrease inflammation, and in colorectal cancer, apart from alleviating some symptoms, they may play a role in the regulation of the cell niche. This review summarizes the main recent findings on the role of cannabinoid receptors, their synthetic or natural ligands and their metabolizing enzymes in normal gastrointestinal function and in disorders including irritable bowel syndrome, inflammatory bowel disease, colon cancer and gastrointestinal chemotherapy-induced adverse effects (nausea/vomiting, constipation, diarrhea).


Subject(s)
Cannabinoids/therapeutic use , Gastrointestinal Diseases/drug therapy , Animals , Cannabinoids/pharmacology , Colorectal Neoplasms/drug therapy , Endocannabinoids/metabolism , Gastrointestinal Motility/drug effects , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/metabolism , Gastrointestinal Tract/physiology , Humans , Inflammatory Bowel Diseases/drug therapy , Visceral Pain/drug therapy , Visceral Pain/etiology
8.
JCI Insight ; 3(11)2018 06 07.
Article in English | MEDLINE | ID: mdl-29875317

ABSTRACT

Functional bowel disorder patients can suffer from chronic abdominal pain, likely due to visceral hypersensitivity to mechanical stimuli. As there is only a limited understanding of the basis of chronic visceral hypersensitivity (CVH), drug-based management strategies are ill defined, vary considerably, and include NSAIDs, opioids, and even anticonvulsants. We previously reported that the 1.1 subtype of the voltage-gated sodium (NaV; NaV1.1) channel family regulates the excitability of sensory nerve fibers that transmit a mechanical pain message to the spinal cord. Herein, we investigated whether this channel subtype also underlies the abdominal pain that occurs with CVH. We demonstrate that NaV1.1 is functionally upregulated under CVH conditions and that inhibiting channel function reduces mechanical pain in 3 mechanistically distinct mouse models of chronic pain. In particular, we use a small molecule to show that selective NaV1.1 inhibition (a) decreases sodium currents in colon-innervating dorsal root ganglion neurons, (b) reduces colonic nociceptor mechanical responses, and (c) normalizes the enhanced visceromotor response to distension observed in 2 mouse models of irritable bowel syndrome. These results provide support for a relationship between NaV1.1 and chronic abdominal pain associated with functional bowel disorders.


Subject(s)
Chronic Pain/drug therapy , Colon/drug effects , Irritable Bowel Syndrome/complications , Visceral Pain/drug therapy , Voltage-Gated Sodium Channel Blockers/administration & dosage , Animals , Chronic Pain/diagnosis , Chronic Pain/etiology , Chronic Pain/pathology , Colon/innervation , Colon/pathology , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Drug Stability , Ganglia, Spinal/cytology , Humans , Irritable Bowel Syndrome/chemically induced , Irritable Bowel Syndrome/pathology , Male , Maximum Tolerated Dose , Mice , NAV1.1 Voltage-Gated Sodium Channel/metabolism , Nociceptors/drug effects , Nociceptors/metabolism , Pain Measurement , Trinitrobenzenesulfonic Acid/administration & dosage , Trinitrobenzenesulfonic Acid/toxicity , Visceral Pain/diagnosis , Visceral Pain/etiology , Visceral Pain/pathology
9.
Acupunct Med ; 36(4): 240-246, 2018 08.
Article in English | MEDLINE | ID: mdl-29720377

ABSTRACT

BACKGROUND: Treatment with electroacupuncture (EA) at ST25 and CV12 has a significant analgesic effect on postinflammatory irritable bowel syndrome (PI-IBS) visceral pain. Enterochromaffin (EC) cells and serotonin (5-hydroxytryptamine (5-HT)) are important in the development of visceral hyperalgesia. OBJECTIVE: To investigate the analgesic effect and underlying mechanisms of EA at ST25 and CV12 on the treatment of trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS visceral hyperalgesia in rats. METHODS: After EA at ST25 and CV12, changes in abdominal withdrawal reflex (AWR), electromyography (EMG) recordings, colonic EC cell numbers, and expression of tryptophan hydroxylase (TPH), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) of TNBS-induced PI-IBS visceral hyperalgesia in rats were examined. RESULTS: The results of AWR tests and EMG recordings indicated a significant analgesic effect of EA stimulation at ST25 and CV12on PI-IBS visceral hyperalgesia (p<0.05). In addition, the increased EC cell numbers and colonic expression of TPH and 5-HT in rats with TNBS-induced PI-IBS visceral hyperalgesia were significantly reduced by EA (p<0.05). CONCLUSIONS: EA stimulation at ST25 and CV12 can attenuate visceral hyperalgesia. This analgesic effect may be mediated via reduction of both colonic EC cell number and 5-HT concentration.


Subject(s)
Acupuncture Analgesia , Acupuncture Points , Electroacupuncture , Irritable Bowel Syndrome/complications , Visceral Pain/therapy , Animals , Humans , Male , Rats , Rats, Sprague-Dawley , Serotonin/metabolism , Tryptophan Hydroxylase/genetics , Tryptophan Hydroxylase/metabolism , Visceral Pain/etiology , Visceral Pain/genetics , Visceral Pain/metabolism
10.
World J Gastroenterol ; 23(33): 6065-6076, 2017 Sep 07.
Article in English | MEDLINE | ID: mdl-28970722

ABSTRACT

AIM: To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. METHODS: Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice (n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential (TRP), sodium and acid-sensing ion channels (ASICs) as well as opioid receptors and guanylate cyclase C (GC-C). RESULTS: Results showed that two opioids and a GC-C agonist, morphine, asimadoline and linaclotide, respectively, the TRP antagonists, AMG9810 and HC-030031 and the sodium channel blocker, carbamazepine, elicited a dose- and/or time-dependent attenuation of referred visceral hypersensitivity, while the ASIC blocker, amiloride, was ineffective at all doses tested. CONCLUSION: Together, these findings implicate opioid receptors, GC-C, and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly, these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties.


Subject(s)
Analgesics/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Hyperalgesia/pathology , Stomach Ulcer/complications , Visceral Pain/pathology , Acetanilides/therapeutic use , Acid Sensing Ion Channel Blockers/therapeutic use , Acid Sensing Ion Channels/metabolism , Acrylamides/therapeutic use , Amiloride/therapeutic use , Analgesics, Opioid/therapeutic use , Animals , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Disease Models, Animal , Drug Evaluation, Preclinical/methods , Humans , Hyperalgesia/drug therapy , Hyperalgesia/etiology , Male , Mice , Morphine/therapeutic use , Pain Measurement/methods , Purines/therapeutic use , Random Allocation , Receptors, Atrial Natriuretic Factor/metabolism , Receptors, Opioid/agonists , Receptors, Opioid/metabolism , Stomach Ulcer/chemically induced , Transient Receptor Potential Channels/antagonists & inhibitors , Transient Receptor Potential Channels/metabolism , Visceral Pain/etiology
11.
Gut ; 66(5): 966-974, 2017 05.
Article in English | MEDLINE | ID: mdl-28232472

ABSTRACT

This review introduces the principles of visceral sensation and appraises the current approaches to management of visceral pain in functional GI diseases, principally IBS. These approaches include dietary measures including fibre supplementation, low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and pharmacological approaches such as antispasmodics, peppermint oil, antidepressants (tricyclic agents, selective serotonin reuptake inhibitors), 5-HT3 receptor antagonists (alosetron, ondansetron, ramosetron), non-absorbed antibiotic (rifaximin), secretagogues (lubiprostone, linaclotide), µ-opioid receptor (OR) and κ-OR agonist, δ-OR antagonist (eluxadoline), histamine H1 receptor antagonist (ebastine), neurokinin-2 receptor antagonist (ibodutant) and GABAergic agents (gabapentin and pregabalin). Efficacy and safety are discussed based on pivotal trials or published systematic reviews and meta-analysis, expressing ORs or relative risks and their 95% CIs. Potential new approaches may be based on recent insights on mucosal expression of genes, and microRNA and epigenetic markers in human biopsies and in animal models of visceral hypersensitivity.The objectives of this review are to appraise the physiology and anatomy of gut sensation and the efficacy in the relief of visceral pain (typically in IBS) of several classes of therapies. These include fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and different classes of medications (box 1). Box 1Classes of pharmacological agents for visceral painAntidepressants (tricyclic agents, selective serotonin reuptake inhibitors)Peppermint oil5-HT3 receptor antagonists (alosetron, ondansetron, ramosetron)Non-absorbed antibiotic (rifaximin)Secretagogues (lubiprostone, linaclotide)µ-Opioid receptor (OR) and κ-OR agonist and δ-OR antagonist (eluxadoline)Histamine H1 receptor antagonist (ebastine)Neurokinin-2 receptor antagonist (ibodutant)GABAergic agents (gabapentin and pregabalin).


Subject(s)
Abdominal Pain/diet therapy , Abdominal Pain/drug therapy , Irritable Bowel Syndrome/complications , Visceral Pain/diet therapy , Visceral Pain/drug therapy , Abdominal Pain/etiology , Anti-Infective Agents/therapeutic use , Antidepressive Agents/therapeutic use , Butyrophenones/therapeutic use , Dipeptides/therapeutic use , GABA Agents/therapeutic use , Gastrointestinal Agents/therapeutic use , Histamine H1 Antagonists/therapeutic use , Humans , Imidazoles/therapeutic use , Mentha piperita , Parasympatholytics/therapeutic use , Phenylalanine/analogs & derivatives , Phenylalanine/therapeutic use , Piperidines/therapeutic use , Plant Oils/therapeutic use , Probiotics/therapeutic use , Quaternary Ammonium Compounds/therapeutic use , Rifamycins/therapeutic use , Rifaximin , Serotonin 5-HT3 Receptor Antagonists/therapeutic use , Thiophenes/therapeutic use , Visceral Pain/etiology , Visceral Pain/physiopathology
12.
Pancreas ; 46(2): 170-176, 2017 02.
Article in English | MEDLINE | ID: mdl-28060186

ABSTRACT

OBJECTIVES: Many patients with painful chronic pancreatitis (CP) have insufficient effect of treatment, and the prevalence of adverse effects is high. Consequently, alternatives to conventional management are needed. We aimed to study the effect of acupuncture in painful CP. METHODS: This was a prospective, single-blinded, randomized crossover trial. Fifteen patients with CP were assigned to a session of acupuncture followed by sham stimulation or vice versa. Patients rated clinical pain scores daily on a 0 to 10 visual analogue scale (VAS) and completed the Patient Global Impression of Change. For mechanistic linkage, resting state electroencephalograms were recorded and quantified by spectral power analysis to explore effects on central pain processing. RESULTS: Acupuncture, compared with sham stimulation, caused more pain relief (2.0 ± 1.5 VAS vs 0.7 ± 0.8 VAS; P = 0.009). The effect, however, was short, and after 1-week follow-up, there was no difference in clinical pain scores between groups (P = 1.0) or the rating of Patient Global Impression of Change (P = 0.8). Electroencephalogram spectral power distributions between sham and acupuncture were comparable between groups (all P > 0.6). CONCLUSIONS: The study presents proof-of-concept for the analgesic effect of acupuncture in pancreatic pain. Although the effect was short lasting, the framework may be used to conceptualize future trials of acupuncture in visceral pain.


Subject(s)
Acupuncture Therapy/methods , Pain Measurement/methods , Pancreatitis, Chronic/complications , Visceral Pain/therapy , Adult , Aged , Cross-Over Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Single-Blind Method , Treatment Outcome , Visceral Pain/diagnosis , Visceral Pain/etiology
13.
Schmerz ; 29(5): 496-502, 2015 Oct.
Article in German | MEDLINE | ID: mdl-26271911

ABSTRACT

Chronic visceral pain is an unresolved neurobiological, medical and socioeconomic challenge. Up to 20% of the adult population suffer from chronic visceral pain and abdominal complaints constitute a prevalent symptom also in children and adolescents. Existing treatment approaches are often unsuccessful and patients typically suffer from multiple somatic and psychological symptoms. This complex situation requires integrative treatment approaches. This review summarizes current basic and clinical research on acute and chronic visceral pain with a focus on research groups in Germany. Despite significant clinical and scientific advances, a number of questions remain open calling for more funding to support research to elucidate the complex pathophysiology of chronic visceral pain and to develop and test new treatment approaches. Research support should focus on interdisciplinary concepts and methodology using expertise from multiple disciplines. The field would also benefit from a broader integration of visceral pain into teaching curricula in medicine and psychology and should aim to motivate young clinicians and scientists to strive for a career within this important and highly fascinating area.


Subject(s)
Visceral Pain/epidemiology , Visceral Pain/etiology , Adolescent , Adult , Animals , Biomedical Research/education , Child , Chronic Pain/epidemiology , Chronic Pain/etiology , Chronic Pain/physiopathology , Chronic Pain/therapy , Cross-Sectional Studies , Disease Models, Animal , Education, Medical/trends , Forecasting , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/therapy , Humans , Integrative Medicine , Interdisciplinary Communication , Intersectoral Collaboration , Pelvic Pain/epidemiology , Pelvic Pain/etiology , Pelvic Pain/physiopathology , Pelvic Pain/therapy , Visceral Pain/physiopathology , Visceral Pain/therapy
14.
Int J Psychophysiol ; 98(1): 128-34, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26209434

ABSTRACT

This study aimed to investigate affective modulation of eye blink startle by aversive visceral stimulation. Startle blink EMG responses were measured in 31 healthy participants receiving painful, intermittent balloon distentions in the distal esophagus during 4 blocks (positive, negative, neutral or no pictures), and compared with startles during 3 'safe' blocks without esophageal stimulations (positive, negative or neutral emotional pictures). Women showed enhanced startle during blocks with distentions (as compared with 'safe' blocks), both when the balloon was in inflated and deflated states, suggesting that fear and/or expectations may have played a role. Men's startle did not differ between distention and non-distention blocks. In this particular study context affective picture viewing did not further impose any effect on startle eye blink responses. The current results may contribute to a better understanding of emotional reactions to aversive interoceptive stimulation.


Subject(s)
Reflex, Startle/physiology , Visceral Pain/physiopathology , Visceral Pain/psychology , Acoustic Stimulation/adverse effects , Adult , Analysis of Variance , Electromyography , Esophagus/innervation , Fear/psychology , Female , Galvanic Skin Response , Humans , Judgment , Male , Physical Stimulation/adverse effects , Self Report , Visceral Pain/etiology , Visual Analog Scale , Young Adult
15.
Purinergic Signal ; 11(3): 321-9, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25809868

ABSTRACT

The aim of this study is to investigate the role of the purinergic receptor P2X3 in the peripheral and central nervous systems during acupuncture treatment for the visceral pain of irritable bowel syndrome (IBS). A total of 24 8-day-old Sprague-Dawley (SD) neonatal male rats (SPF grade) were stimulated using colorectal distention (CRD) when the rats were awake. The modeling lasted for 2 weeks with one stimulation per day. After 6 weeks, the rats were randomly divided into three groups of eight each: (1) the normal group (NG, n = 8); (2) the model group (MG, n = 8); and (3) the model + electroacupuncture group (EA, n = 8) that received electroacupuncture at a needling depth of 5 mm at the Shangjuxu (ST37, bilateral) and Tianshu (ST25, bilateral) acupoints. The parameters of the Han's acupoint nerve stimulator (HANS) were as follows: sparse-dense wave with a frequency of 2/100 Hz, current of 2 mA, 20 min/stimulation, and one stimulation per day; the treatment was provided for seven consecutive days. At the sixth week after the treatment, the abdominal withdrawal reflex (AWR) score was determined; immunofluorescence and immunohistochemistry were used to measure the expression of the P2X3 receptor in myenteric plexus neurons, prefrontal cortex, and anterior cingulate cortex; and, a real-time PCR assay was performed to measure the expression of P2X3 messenger RNA (mRNA) in the dorsal root ganglion (DRG) and spinal cord. After stimulation with CRD, the expression levels of the P2X3 receptor in the inter-colonic myenteric plexus, DRG, spinal cord, prefrontal cortex, and anterior cingulate cortex were upregulated, and the sensitivity of the rats to IBS visceral pain was increased. Electroacupuncture (EA) could downregulate the expression of the P2X3 receptor and ease the sensitivity to visceral pain. The P2X3 receptor plays an important role in IBS visceral pain. The different levels of P2X3 in the peripheral enteric nervous system and central nervous system mediate the effects of the EA treatment of the visceral hyperalgesia of IBS.


Subject(s)
Central Nervous System/physiopathology , Electroacupuncture , Irritable Bowel Syndrome/complications , Irritable Bowel Syndrome/physiopathology , Peripheral Nervous System/physiopathology , Receptors, Purinergic P2X3 , Visceral Pain/physiopathology , Visceral Pain/therapy , Acupuncture Points , Animals , Animals, Newborn , Down-Regulation , Enteric Nervous System/physiopathology , Male , Pain Measurement , RNA, Messenger/biosynthesis , Rats , Rats, Sprague-Dawley , Receptors, Purinergic P2X3/biosynthesis , Receptors, Purinergic P2X3/genetics , Visceral Pain/etiology
16.
Neurogastroenterol Motil ; 27(6): 775-86, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25810326

ABSTRACT

BACKGROUND: We previously reported estrogen modulates spinal N-methyl-d-aspartate (NMDA) receptor processing of colorectal pain through changes in spinal GluN1 subunit phosphorylation/expression. The purpose of this study was to investigate whether spinal GluN2B containing NMDA receptors are involved in estrogen modulation of visceral pain processing. METHODS: Behavioral, molecular, and immunocytochemical techniques were used to determine spinal GluN2B expression/phosphorylation and function 48 h following subcutaneous injection of estradiol (E2) or vehicle (safflower oil, Saff oil) in ovariectomized rats in the absence or presence of colonic inflammation induced by mustard oil. KEY RESULTS: E2 increased the magnitude of the visceromotor response (VMR) to colorectal distention compared to Saff oil in non-inflamed rats. Intrathecal injection of the GluN2B subunit antagonist, Ro 25-6981, had no effect on the VMR in non-inflamed E2 or Saff oil rats. Colonic inflammation induced visceral hyperalgesia in E2, but not Saff oil rats. Visceral hyperalgesia in E2 rats was blocked by intrathecal GluN2B subunit selective antagonists. In inflamed rats, E2 increased GluN2B protein and gene expression in the thoracolumbar (TL), but not lumbosacral (LS), dorsal spinal cord. Immunocytochemical labeling showed a significant increase in GluN2B subunit in the superficial dorsal horn of E2 rats compared to Saff oil rats. CONCLUSIONS & INFERENCES: These data support the hypothesis that estrogen increases spinal processing of colonic inflammation-induced visceral hyperalgesia by increasing NMDA receptor activity. Specifically, an increase in the activity of GluN2B containing NMDA receptors in the TL spinal cord by estrogen underlies visceral hypersensitivity in the presence of colonic inflammation.


Subject(s)
Behavior, Animal , Colitis/metabolism , Estradiol/pharmacology , Estrogens/pharmacology , Hyperalgesia/metabolism , Receptors, N-Methyl-D-Aspartate/drug effects , Spinal Cord/drug effects , Visceral Pain/metabolism , Animals , Colitis/chemically induced , Colitis/complications , Female , Hyperalgesia/etiology , Immunohistochemistry , Lumbar Vertebrae , Mustard Plant , Ovariectomy , Phenols/pharmacology , Phosphorylation , Piperidines/pharmacology , Plant Oils , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/metabolism , Spinal Cord/metabolism , Thoracic Vertebrae , Visceral Pain/etiology
17.
Eur J Pharmacol ; 745: 190-5, 2014 Dec 15.
Article in English | MEDLINE | ID: mdl-25446429

ABSTRACT

Visceral pain, especially in the abdominal region, represents one of the most common types of pain. Its chronic form is usually very hard to treat by conventional analgesic agents and adjuvants. We investigated the antinociceptive effect of botulinum toxin type A (BTX-A) in male Wistar rats in two models of visceral pain: peritonitis induced by intraperitoneal injection of 1% acetic acid and colitis induced by intracolonic instillation of 0.1% capsaicin. Pain was measured as the number of abdominal writhes. Additionally, referred mechanical sensitivity in the ventral abdominal area was evaluated by von Frey test and the extent of spinal c-Fos expression was immunohistochemically examined. BTX-A significantly reduced the number of abdominal writhes in both models of visceral pain after intrathecal application in a dose of 2 U/kg. In the experimental colitis model, BTX-A (2 U/kg) reduced both referred mechanical allodynia and c-Fos expression in the dorsal horn of the spinal cord (S2/S3 segments). In contrast to intrathecal administration, BTX-A (2 U/kg) administered into the cisterna magna had no effect on pain suggesting that the primary site of its action is a spinal cord.


Subject(s)
Abdominal Pain/drug therapy , Analgesics/therapeutic use , Botulinum Toxins, Type A/therapeutic use , Abdominal Pain/etiology , Abdominal Pain/physiopathology , Acetic Acid/toxicity , Analgesics/administration & dosage , Animals , Botulinum Toxins, Type A/administration & dosage , Capsaicin/toxicity , Colitis/complications , Colitis/physiopathology , Disease Models, Animal , Hyperalgesia/drug therapy , Hyperalgesia/etiology , Hyperalgesia/physiopathology , Male , Pain Measurement , Pain, Referred/drug therapy , Pain, Referred/etiology , Pain, Referred/physiopathology , Peritonitis/complications , Peritonitis/physiopathology , Proto-Oncogene Proteins c-fos/metabolism , Rats , Rats, Wistar , Spinal Cord/drug effects , Spinal Cord/physiopathology , Visceral Pain/drug therapy , Visceral Pain/etiology , Visceral Pain/physiopathology
18.
Acupunct Med ; 32(6): 472-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25193927

ABSTRACT

OBJECTIVE: To investigate the effects and mechanisms of action of auricular electroacupuncture (AEA) on visceral pain induced by colorectal distension (CRD). METHODS: Twenty-nine female Sprague-Dawley rats were randomly divided into four groups: control; untreated CRD; CRD+AEA; and CRD+sham electroacupuncture (SEA). An electromyogram (EMG) was recorded for 120 min in the conscious state. After a 30 min baseline recording, CRD was performed in untreated CRD, AEA and SEA groups and lasted for 90 min. AEA and SEA were started at 30 min and lasted for 30 min. The EMG was recorded and analysed to evaluate the severity of visceral pain, indicated by the magnitude of the vasomotor response (VMR). mRNA expression of the 5-hydroxytryptamine 1a (5-HT1a) receptor was measured separately in the colon and raphe nuclei using real-time fluorescent quantitative PCR. RESULTS: No differences were seen in the baseline EMG among the four groups (p>0.05). During pre-stimulation, VMR magnitude in the CRD, AEA and SEA groups increased compared with that in the control group (p<0.05). During stimulation, the VMR magnitude was significantly decreased in AEA but not SEA groups relative to the (untreated) CRD group. Similarly, mRNA expression of the 5-HT1a receptor in both the colon and raphe nuclei was lower in AEA but not SEA groups compared with the CRD group (p<0.05). CONCLUSIONS: AEA can ameliorate CRD-induced visceral pain in rats, and increase mRNA expression of the 5-HT1a receptor peripherally (in the colon) and centrally (in the raphe nuclei), suggesting a serotonergic mechanism of action.


Subject(s)
Acupuncture, Ear , Colon/metabolism , Electroacupuncture , Raphe Nuclei/metabolism , Visceral Pain/therapy , Animals , Colon/injuries , Colon/pathology , Dilatation, Pathologic , Electromyography , Female , RNA, Messenger/metabolism , Random Allocation , Rats, Sprague-Dawley , Receptor, Serotonin, 5-HT1A/genetics , Receptor, Serotonin, 5-HT1A/metabolism , Severity of Illness Index , Vasomotor System , Visceral Pain/etiology , Visceral Pain/metabolism
19.
Pain Pract ; 13(1): 3-17, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22521096

ABSTRACT

Chronic pelvic pain (CPP) is complex and often resistant to treatment. While the exact pathophysiology is unknown, the pain states resultant from conditions such as interstitial cystitis and the like yield patients with a presentation that bears a striking similarity to neuropathic syndromes that are known to respond to neuromodulation. While there has been past success using the sacral region as a target for spinal cord stimulation (SCS) to treat these patients, there remains to be a consensus on the optimal location for lead placement. In this article, the authors discuss the potential etiology of CPP, examine the current literature on lead placement for SCS as a method of treatment, as well as present several cases where novel lead placement was successfully employed.


Subject(s)
Electric Stimulation Therapy/methods , Neurotransmitter Agents/therapeutic use , Visceral Pain/therapy , Adult , Aged , Animals , Female , Humans , Male , Middle Aged , Treatment Outcome , Visceral Pain/classification , Visceral Pain/etiology
20.
Neuromodulation ; 14(1): 8-12; discussion 12, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21992155

ABSTRACT

INTRODUCTION: Acupuncture has been used for treating various gastrointestinal (GI) diseases. However, the mechanism of acupuncture 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.


Subject(s)
Acupuncture , Gastrointestinal Tract/innervation , Neurotransmitter Agents/metabolism , Parasympathetic Nervous System/physiology , Sympathetic Nervous System/physiology , Acupuncture Therapy , Afferent Pathways/physiology , Animals , Gastrointestinal Diseases/complications , Gastrointestinal Diseases/physiopathology , Gastrointestinal Diseases/therapy , Gastrointestinal Tract/physiology , Gastrointestinal Tract/physiopathology , Humans , Reflex/physiology , Visceral Pain/etiology , Visceral Pain/physiopathology , Visceral Pain/therapy
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