Hot-Water Bathing Improves Symptoms in Patients with Cyclic Vomiting Syndrome and Is Modulated by Chronic Cannabis Use.

BACKGROUND: Cyclic vomiting syndrome (CVS) is a chronic functional GI disorder; a characteristic compulsive "hot-water bathing" pattern is reported to alleviate symptoms during an acute episode. There is limited data on this bathing pattern: proposed mechanisms include core temperature increase via effects on cannabinoid type 1 receptors in the brain, skin transient receptor potential vanilloid 1 receptor stimulation, and blood flow shift from viscera to skin. AIMS: We thus sought to characterize the hot-water bathing pattern in patients with CVS and identify differences between heavy cannabis users in comparison to occasional and non-users. METHODS: We conducted a cross-sectional study of 111 patients with CVS at a single tertiary referral center. Questionnaires regarding clinical characteristics, hot-water bathing, and cannabis use were administered. Patients were classified based on cannabis usage into regular cannabis users (≥ 4 times/week), and occasional + non-users (< 4 times/week and no current use). RESULTS: A total of 81 (73%) respondents reported the hot-water bathing behavior during an episode. The majority (> 80%) noted a marked improvement in nausea, vomiting, abdominal pain and symptoms associated with panic. Regular cannabis users were more likely to use "very-hot" water (50% vs. 16%, p = 0.01) and time to relief of symptoms was longer (> 10 min) in this group, compared to the rest of the cohort. CONCLUSIONS: Hot-water bathing relieves both GI and symptoms related to panic in most patients which appear to be modulated by chronic cannabis use. These findings can help inform future physiologic studies in CVS pathogenesis.

The role of acupuncture in the treatment of chronic pain.

Acupuncture is a practice based on traditional Chinese medicine, in which needles are used to restore the body's internal balance. Recently, there has been growing interest in the use of acupuncture for various pain conditions. Acupuncture's efficacy in five pain conditions-low back pain (LBP), migraines, fibromyalgia, neck pain, and abdominal pain-was evaluated in this evidence-based, comprehensive review. Based on the most recent evidence, migraine and fibromyalgia are two conditions with the most favorable outcomes after acupuncture. At the same time, abdominal pain has the least evidence for the use of acupuncture. Acupuncture is efficacious for reducing pain in patients with LBP, and for short-term pain relief for those with neck pain. Further research needs to be done to evaluate acupuncture's efficacy in these conditions, especially for abdominal pain, as many of the current studies have a risk of bias due to lack of blinding and small sample size.

Impaired Vagal Efficiency Predicts Auricular Neurostimulation Response in Adolescent Functional Abdominal Pain Disorders.

INTRODUCTION: To determine whether pretreatment vagal efficiency (VE), respiratory sinus arrhythmia, and heart period can predict pain improvement with auricular neurostimulation in pediatric functional abdominal pain disorders. METHODS: A total of 92 adolescents with functional abdominal pain disorders underwent a 4-week randomized, double-blinded, sham-controlled auricular neurostimulation trial. Electrocardiogram-derived variables at baseline were used to predict pain using mixed effects modeling. RESULTS: A 3-way interaction (95% confidence intervals: 0.004-0.494) showed that the treatment group subjects with low baseline VE had lower pain scores at week 3. There was no substantial change in the placebo or high VE treatment group subjects. This effect was supported by a significant correlation between baseline VE and degree of pain reduction only in the treatment group. DISCUSSION: Impaired cardiac vagal regulation measured by VE predicts pain improvement with auricular neurostimulation.

Study on intelligent syndrome differentiation neural network model of stomachache in traditional Chinese medicine based on the real world.

Stomachache is not only disease name of Traditional Chinese medicine (TCM) but also the clinical symptom. It is a common and multiple diseases. TCM has its particular advantage in clinical treatment of stomachache. Syndrome differentiation is an important concept in TCM practice. The therapeutic process is virtually a nonlinear mapping process from clinical symptom to syndrome diagnosis with processing and seeking rules from mass data. Artificial neutral network has strong learning ability for nonlinear relationship. Artificial neutral network has been widely used to TCM area where the multiple factors, multilevel, nonlinear problem accompanied by a large number of optimization exist.We present an original experimental method to apply the improved third-order convergence LM algorithm to intelligent syndrome differentiation for the first time, and compare the predicted ability of Levenberg-Marquardt (LM) algorithm and the improved third-order convergence LM algorithm in syndrome differentiation.In this study, 2436 cases of stomachache electronic medical data from hospital information system, and then the real world data were normalized and standardized. Afterwards, LM algorithm and the improved third-order convergence LM algorithm were used to build the Back Propagation (BP) neural network model for intelligent syndrome differentiation of stomachache on Matlab, respectively. Finally, the differentiation performance of the 2 models was tested and analyzed.The testing results showed that the improved third-order convergence LM algorithm model has better average prediction and diagnosis accuracy, especially in predicting "liver-stomach disharmony" and "stomach yang deficiency", is above 95%.By effectively using the self-learning and auto-update ability of the BP neural network, the intelligent syndrome differentiation model of TCM can fully approach the real side of syndrome differentiation, and shows excellent predicted ability of syndrome differentiation.

Desensitization of transient receptor potential vanilloid type-1 (TRPV1) channel as promising therapy of irritable bowel syndrome: characterization of the action of palvanil in the mouse gastrointestinal tract.

TRPV1 are involved in the control of the gastrointestinal (GI) functions and pain sensation. Their activation induces pain but it is followed by desensitization, which in turn causes analgesia. The studies from the last two decades indicate that TRPV1 are involved in visceral hypersensitivity in the GI tract and pathogenesis of irritable bowel syndrome (IBS). Therefore, the aim of this study is to assess the action of fast desensitizing agonist of TRPV1, palvanil (N-palmitoyl-vanillamine), in the murine GI tract and on nociception to evaluate its potential application in the therapy of IBS. The effect of palvanil on smooth muscle contractility was evaluated using organ baths. The impact of palvanil on intestinal secretion was assessed in Ussing chambers. In vivo, the action of palvanil (0.1-1 mg/kg) was assessed in whole GI transit, fecal pellet output, and colonic bead expulsion tests. The antinociceptive potency of palvanil was tested in the mustard oil-induced pain test. Palvanil inhibited colonic contractions (evoked by electrical field stimulation, EFS) and decreased the ion transport in the colon stimulated with forskolin. It did not affect secretion in experiments with veratridine. In vivo, palvanil prolonged whole GI transit at all doses tested. At the lower dose tested, it accelerated colonic motility during first 60 min following injection. By contrast, at the dose of 1 mg/kg, colonic motility was inhibited. Palvanil induced antinociceptive action at all tested doses in mustard oil-induced pain test. TRPV1 fast-desensitizing compounds, i.e., palvanil, may be promising agents in the therapy of IBS since it modulates intestinal motility and reduces visceral pain.

New advances in the treatment of paediatric functional abdominal pain disorders.

This Review summarises recent pharmacological and upcoming alternative interventions for children with functional abdominal pain disorders (FAPDs). Pharmacological targets include prokinetics and drugs affecting gastric accommodation to treat postprandial distress and nausea. Similarly, anti-inflammatory agents, junctional protein regulators, analgesics, secretagogues, and serotonin antagonists have a therapeutic role for irritable bowel syndrome. Non-pharmacological treatments include peripheral electrical nerve field stimulation to the external ear, gastric electrical stimulation, dietary interventions such as low fructose and fibre based diets, and nutraceuticals, which include probiotics, prebiotics, and synbiotics. Newer psychological advances such as exposure-based cognitive behavioural therapy, acceptance and commitment therapy, and mindfulness meditation are being investigated for paediatric functional pain. Lastly, alternative therapies such as acupuncture, moxibustion, yoga, and spinal manipulation are also gaining popularity in the treatment of FAPDs.

Postprandial distress syndrome: stratification and management.

INTRODUCTION: Functional dyspepsia (FD), defined by the Rome consensus as the presence of functional symptoms originating from the gastroduodenum, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. We used a literature search for a narrative review on the current state of knowledge regarding PDS. Areas covered: Epidemiological studies support PDS as a separate entity and the biggest FD subgroup. The pathophysiology of PDS is heterogeneous, and disorders of gastric sensorimotor function as well as low grade duodenal inflammation have been implicated. Although prokinetic agents may provide the most pathophysiology-oriented treatment option, there is a paucity of suitable agents, and proton pump inhibitors are the traditional first-line therapy. Other options include agents that enhance gastric accommodation, such as acotiamide and 5-HT1A agonists, neuromodulators such as mirtazapine, and traditional medicine approaches. Expert commentary: PDS is highly prevalent, with probably heterogeneous underlying pathophysiology. Motility modifying agents and neuromodulators are the cornerstone of PDS therapy, but there is a need for high quality studies of new therapeutic approaches.

Acupuncture for irritable bowel syndrome: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and change of bowel habit without organic disease. A global perspective given by the World Gastroenterology Organization (WGO) points out that IBS can impact the quality of an individual's daily life, cause socioeconomic problems and potentially impair the patient-physician relationship. It remains a problem to treat IBS due to the complicated pathophysiology. Acupuncture is an alternative therapy recommended for IBS. The aim of this study is to investigate the efficacy and safety of acupuncture therapy for patients with IBS. We also want to explore the correlation between IBS-gene subtypes and acupuncture effect. METHODS/DESIGN: A multicenter randomized controlled trial will be performed in seven hospitals. Six hundred participants will be stratified into two strata (IBS-C or IBS-D). Then, patients within each stratum will be divided into an experimental group and a control group randomly. The experimental group is treated with acupuncture while the control group is treated with Western medicine. All the patients will receive a 6-week treatment and a 3-month follow-up. The primary outcome is the IBS-Symptom Severity Score (IBS-SSS), the secondary outcome is the score of the IBS-Quality of Life (IBS-QoL).The correlation between IBS-gene subtypes and acupuncture effect will be detected based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Outcome measures (including primary and secondary outcome measures) are collected at baseline,1 week, 2 weeks, 4 weeks, and 6 weeks of the intervention, and 12 weeks after the intervention. DISCUSSION: This is a multicenter randomized controlled trial for IBS in China. It may clarify the efficacy of acupuncture as an alternative therapy for IBS. This is the first time ever that the potential mechanism of IBS based on genomics has been investigated. TRIAL REGISTRATION: Chinese Clinical Trials Register, ID: ChiCTR-IOR-15006259 . First registered on 14 April 2015.

Effect of electroacupuncture at homotopic and heterotopic acupoints on abdominal pain in patients with irritable bowel syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Acupuncture has been widely applied in the clinic to treat irritable bowel syndrome (IBS), but the underlying mechanism remains unknown. Diffuse noxious inhibitory control (DNIC) is deficient in patients with IBS, which attenuates the systemic analgesic effect elicited by noxious stimulation that is remote from pain areas. Therefore, the aim of this study is to investigate the analgesic effect of electroacupuncture (EA) at homotopic or heterotopic acupoints on abdominal pain in patients with IBS. METHODS/DESIGN: This study is a randomized, single-blinded, controlled, four-arm parallel trial. A total of 144 patients will be randomly assigned to four groups: a homotopic noxious stimulation group (group A), a homotopic innocuous stimulation group (group B), a heterotopic noxious stimulation group (group C), and a heterotopic innocuous stimulation group (group D). Each patient will receive 14 sessions of treatment, twice per week for 7 weeks. The primary outcome will be pain intensity measured with the visual analog scale. The secondary outcomes will include the IBS Symptom Severity Scale, IBS Quality of Life questionnaire, pain threshold (PT), and the Symptom Checklist-90 for psychological distress. The PT will be measured before and after every treatment. All other outcomes will be evaluated before the 1st treatment, after 7th and 14th treatment, and 3 months later during follow-up. DISCUSSION: The aim of this study is to assess the analgesic effect of EA at homotopic (abdomen) acupoints and heterotopic (lower limb) acupoints on abdominal pain in patients with IBS, as well as the difference in analgesic effects between noxious and innocuous stimulation. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-15006879 . Registered on 5 August 2015.

Pediatric irritable bowel syndrome and other functional abdominal pain disorders: an update of non-pharmacological treatments.

INTRODUCTION: Functional abdominal pain disorders, including irritable bowel syndrome, are common in children and treatment can often be difficult. Pharmacological therapies and complementary treatments are widely used, despite the limited data in pediatrics. Areas covered: This review provides an overview of the available data for the use of diet, probiotics, percutaneous electrical nerve stimulation, and psychosocial interventions, including hypnotherapy, yoga, cognitive and behavioral therapy, and mind-body interventions for the treatment of functional abdominal pain disorders in children. The literature review included a PubMed search by each therapy, children, abdominal pain, and irritable bowel syndrome. Relevant articles to this review are discussed. Expert commentary: The decision on the use of pharmacological and complementary therapies should be based on clinical findings, evidence, availability, and in-depth discussion with the patient and family. The physician should provide education on the different interventions and their role on the treatment in an empathetic and warm manner providing ample time for the family to ask questions.

Review article: the physiological effects and safety of peppermint oil and its efficacy in irritable bowel syndrome and other functional disorders.

BACKGROUND: Peppermint oil has been used for centuries as a treatment for gastrointestinal ailments. It has been shown to have several effects on gastrointestinal physiology relevant to clinical care and management. AIM: To review the literature on peppermint oil regarding its metabolism, effects on gastrointestinal physiology, clinical use and efficacy, and safety. METHODS: We performed a PubMed literature search using the following terms individually or in combination: peppermint, peppermint oil, pharmacokinetics, menthol, oesophagus, stomach, small intestine, gallbladder, colon, transit, dyspepsia, nausea, abdominal pain, and irritable bowel syndrome. Full manuscripts evaluating peppermint oil that were published through 15 July 2017 were reviewed. When evaluating therapeutic indications, only randomised clinical trials were included. References from selected manuscripts were used if relevant. RESULTS: It appears that peppermint oil may have several mechanisms of action including: smooth muscle relaxation (via calcium channel blockade or direct enteric nervous system effects); visceral sensitivity modulation (via transient receptor potential cation channels); anti-microbial effects; anti-inflammatory activity; modulation of psychosocial distress. Peppermint oil has been found to affect oesophageal, gastric, small bowel, gall-bladder, and colonic physiology. It has been used to facilitate completion of colonoscopy and endoscopic retrograde cholangiopancreatography. Placebo controlled studies support its use in irritable bowel syndrome, functional dyspepsia, childhood functional abdominal pain, and post-operative nausea. Few adverse effects have been reported in peppermint oil trials. CONCLUSION: Peppermint oil is a natural product which affects physiology throughout the gastrointestinal tract, has been used successfully for several clinical disorders, and appears to have a good safety profile.

Histamine H1 Receptor Antagonists Facilitate Electroacupuncture Analgesia.

This study investigated the influence of the histamine H1 receptor antagonists, chlorpheniramine (CHL) and pyrilamine, on the analgesic effects of acupuncture in mice. Nociceptive response was evaluated by the acetic acid-induced abdominal writhe test. Electroacupuncture (EA) at bilateral ST36 reduced the manifestations of acetic acid-induced abdominal writhing, whereas needle insertion without electrostimulation had no such effect. Notably, EA treatment was not associated with any analgesic effects in mice pretreated with naloxone. Low doses of CHL (0.6[Formula: see text]mg/kg; p.o.) or pyrilamine (2.5[Formula: see text]mg/kg; i.p.) as monotherapy did not affect acetic acid-induced abdominal writhing. However, when each agent was combined with EA, acetic acid-induced abdominal writhing was reduced by a greater extent when compared with EA alone. Interestingly, the effects of CHL on acupuncture analgesia were not completely reversed by naloxone treatment. Acetic acid induced increases of phospho-p38 expression in spinal cord, as determined by immunofluorescence staining and Western blot analysis. These effects were attenuated by EA at ST36 and by low doses of histamine H1 receptor antagonists, alone or in combination. Our findings show that relatively low doses of histamine H1 receptor antagonists facilitate EA analgesia via non-opioid receptors. These results suggest a useful strategy for increasing the efficacy of EA analgesia in a clinical situation.

Psychoneuroimmunological approach to gastrointestinal related pain.

BACKGROUND AND PURPOSE (AIMS): Psychoneuroimmunology is both a theoretical and practical field of medicine in which human biology and psychology are considered an interconnected unity. Through such a framework it is possible to elucidate complex syndromes in gastrointestinal related pain, particularly chronic non-malignant. The aim is to provide insight into pathophysiological mechanisms and suggest treatment modalities according to a comprehensive paradigm. The article also presents novel findings that may guide clinicians to recognize new targets or scientists to find new research topics. METHODS: A literature search of 'PubMed' and 'Google Scholar' databases was performed. Search terms included: 'Visceral pain', 'Psychoneuroimmunology', 'Psychoneuroimmunology and pain', 'Pain in GI system', 'GI related pain', 'Pain and microbiota', 'Enteric nervous system', 'Enteric nervous system and inflammation', 'CNS and pain', 'Inflammation and pain in GI tract', 'Neurogastroenterology', 'Neuroendocrinology', 'Immune system in GI pain'. After searching and reading sources deemed recent and relevant, a narrative review was written with a tendency to discriminate the peripheral, intermediate, and central pathophysiological mechanisms or treatment targets. RESULTS: Recent evidence point out the importance of considering the brain-gut axis as the main connector of the central and peripheral phenomena encountered in patients suffering from chronic non-malignant gastrointestinal related pain. This axis is also a prime clinical target with multiple components to be addressed in order for therapy to be more effective. Patients suffering from inflammatory bowel disease or functional gastrointestinal disorders represent groups that could benefit most from the proposed approach. CONCLUSIONS (BASED ON OUR FINDINGS): Rather than proceeding with established allopathic single-target central or peripheral treatments, by non-invasively modulating the brain-gut axis components such as the psychological and neuroendocrinological status, microbiota, enteric nervous system, or immune cells (e.g. glial or mast cells), a favourable clinical outcome in various chronic gastrointestinal related pain syndromes may be achieved. Clinical tools are readily available in forms of psychotherapy, prebiotics, probiotics, nutritional advice, and off-label drugs. An example of the latter is low-dose naltrexone, a compound which opens the perspective of targeting glial cells to reduce neuroinflammation and ultimately pain. IMPLICATIONS (OUR OPINION ON WHAT OUR FINDINGS MEAN): Current findings from basic science provide sound mechanistic evidence and once entering clinical practice should yield more effective outcomes for patients. In addition to well-established pharmacotherapy comprised notably of anti-inflammatories, antibiotics, and proton-pump inhibitors, valid treatment strategies may contain other options. These disease modulating add-ons include probiotics, prebiotics, food supplements with anti-inflammatory properties, various forms of psychotherapy, and low-dose naltrexone as a glial modulator that attenuates neuroinflammation. Clearly, a broader and still under exploited set of evidence-based tools is available for clinical use.

Pulsed radiofrequency or anterior neurectomy for anterior cutaneous nerve entrapment syndrome (ACNES) (the PULSE trial): study protocol of a randomized controlled trial.

BACKGROUND: Some patients with chronic abdominal pain suffer from an anterior cutaneous nerve entrapment syndrome (ACNES). This somewhat illusive syndrome is thought to be caused by the entrapment of end branches of the intercostal nerves residing in the abdominal wall. If ACNES is suspected, a local injection of an anesthetic agent may offer relief. If pain is recurrent following multiple-injection therapy, an anterior neurectomy entailing removal of the entrapped nerve endings may be considered. After 1 year, a 70% success rate has been reported. Research on minimally invasive alternative treatments is scarce. Pulsed radiofrequency (PRF) treatment is a relatively new treatment for chronic pain syndromes. An electromagnetic field is applied around the nerve in the hope of leading to pain relief. This randomized controlled trial compares the effect of PRF treatment and neurectomy in patients with ACNES. METHODS: Adult ACNES patients having short-lived success following injections are randomized to PRF or neurectomy. At the 8-week follow-up visit, unsuccessful PRF patients are allowed to cross over to a neurectomy. Primary outcome is pain relief after either therapy. Secondary outcomes include patient satisfaction, quality of life, use of analgesics and unanticipated adverse events. The study is terminated 6 months after receiving the final procedure. DISCUSSION: Since academic literature on minimally invasive techniques is lacking, well-designed trials are needed to optimize results of treatment for ACNES. This is the first large, randomized controlled, proof-of-concept trial comparing two therapy techniques in ACNES patients. The first patient was included in October 2015. The expected trial deadline is December 2017. If effective, PRF may be incorporated into the ACNES treatment algorithm, thus minimizing the number of patients requiring surgery. TRIAL REGISTRATION: Nederlands Trial Register (Dutch Trial Register), NTR5131 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5131 ). Registered on 15 April 2015.

Tongxie Formula Reduces Symptoms of Irritable Bowel Syndrome.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is the most common chronic gastrointestinal disorder, yet few drugs are effective in reducing symptoms. Approximately 50% of patients with IBS attempt herbal therapy at least once. We performed a randomized controlled trial to compare the efficacy of the herb formulation tongxie vs placebo or pinaverium (an antispasmodic agent) in reducing symptoms of IBS. METHODS: We performed a trial of 1044 adult patients with IBS (based on Rome III criteria) at 5 hospitals in China, from August 2012 through January 2015. Subjects were randomly assigned (1:1:1) to groups given tongxie (a combination of A macrocephalae, P lactiflora, C reticulata, S divaricata, C pilosula, C wenyujin, C medica, and P cocos, along with other herbs, based on patient features), placebo, or pinaverium (50 mg tablets) 3 times daily for 4 weeks. Primary end points were significantly greater reductions in abdominal pain and Bristol stool score (before vs after the 4-week study period) in patients given tongxie compared with patients given placebo or pinaverium. Secondary end points were reductions in pain and stool frequencies and abdominal discomfort and its frequency. RESULTS: Subjects given tongxie had significant reductions, before vs after the study period, in all 6 symptoms assessed, compared to patients given placebo (P < .001). A significantly higher proportion of patients given tongxie had increased stool consistency (75.6%) than patients given pinaverium (50.6%), and a significantly higher proportion of patients given tongxie had fewer daily stools (72.7%) than subjects given pinaverium (58.3%) (P < .001 for both). However, significantly higher proportions of patients given pinaverium had reduced pain (63.5%) and pain frequency (69.5%) than patients given tongxie (51.4% and 58.6%, respectively; P < .005 for both). CONCLUSIONS: In a randomized controlled trial of patients with IBS in China, we found 4 weeks of tongxie to produce significantly greater reduction in symptoms than placebo, and greater increases in stool consistency and reductions in stool frequency, than patients given pinaverium. Tongxie can therefore be considered an effective alternative therapy for patients with IBS who do not respond well to conventional therapies. Clinicaltrials.gov no: NCT01641224.

Comparison of the analgesic effects between electro-acupuncture and moxibustion with visceral hypersensitivity rats in irritable bowel syndrome.

AIM: To observe whether there are differences in the effects of electro-acupuncture (EA) and moxibustion (Mox) in rats with visceral hypersensitivity. METHODS: EA at 1 mA and 3 mA and Mox at 43 °C and 46 °C were applied to the Shangjuxu (ST37, bilateral) acupoints in model rats with visceral hypersensitivity. Responses of wide dynamic range neurons in dorsal horns of the spinal cord were observed through the extracellular recordings. Mast cells (MC) activity in the colons of rats were assessed, and 5-hydroxytryptamine (5-HT), 5-hydroxytryptamine 3 receptor (5-HT3R) and 5-HT4R expressions in the colons were measured. RESULTS: Compared with normal control group, responses of wide dynamic range neurons in the dorsal horn of the spinal cord were increased in the EA at 1 mA and 3 mA groups (1 mA: 0.84 ± 0.74 vs 2.73 ± 0.65, P < 0.001; 3 mA: 1.91 ± 1.48 vs 6.44 ± 1.26, P < 0.001) and Mox at 43 °C and 46 °C groups (43 °C: 1.76 ± 0.81 vs 4.14 ± 1.83, P = 0.001; 46 °C: 5.19 ± 2.03 vs 7.91 ± 2.27, P = 0.01). MC degranulation rates and the expression of 5-HT, 5-HT3R and 5-HT4R in the colon of Mox 46 °C group were decreased compared with model group (MC degranulation rates: 0.47 ± 0.56 vs 0.28 ± 0.78, P < 0.001; 5-HT: 1.42 ± 0.65 vs 7.38 ± 1.12, P < 0.001; 5-HT3R: 6.62 ± 0.77 vs 2.86 ± 0.88, P < 0.001; 5-HT4R: 4.62 ± 0.65 vs 2.22 ± 0.97, P < 0.001). CONCLUSION: The analgesic effects of Mox at 46 °C are greater than those of Mox at 43 °C, EA 1 mA and EA 3 mA.

Efficacy and safety of manual acupuncture manipulations with different frequencies on epigastric pain syndrome (EPS) in functional dyspepsia (FD) patients: study protocol for a randomized controlled trial.

BACKGROUND: Manual acupuncture (MA) manipulations are one of the key factors influencing acupuncture effects in traditional Chinese medicine theory. Different MA manipulations contain different stimulating parameters, thus generating different acupuncture responses or effects. Evidence has demonstrated that acupuncture is effective for functional dyspepsia (FD). However, the effects of different stimulating parameters of MA manipulations on FD remain unclear. METHODS/DESIGN: This study is a randomized controlled trial with a four-arm, parallel-group structure. Patients with FD with epigastric pain syndrome (EPS) will be included and randomly allocated into four groups: three MA manipulation groups (separately treated with a frequency of 1 Hz, 2 Hz, or 3 Hz) and a control group. All groups will receive omeprazole as a basic treatment and acupuncture: in the MA manipulation groups, the needles will be manipulated manually with three different frequencies on the basis when de qi is reached, while in the control group, the needles will be inserted without any manipulation. All patients will receive acupuncture treatment of five consecutive sessions per week for 2 weeks and be followed up at 4, 8, and 12 weeks. The primary outcomes of the study include patients' response to the treatment. The secondary outcomes include dyspeptic symptoms, quality of life, mental status, fasting serum gastrin, motilin, and ghrelin concentrations, and adverse events. The protocol was approved by the Ethics committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (2016-K-057-01). DISCUSSION: The aim of this study is to evaluate the efficacy and safety of MA manipulations with different stimulating parameters (different frequencies) on EPS in patients with FD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR-16008189 . Registered on 30 March 2016.

Abdominal Trigger Points and Psychological Function.

Myofascial trigger points (TPs) are a poorly understood phenomenon involving the myofascial system and its related neural, lymphatic, and circulatory elements. Compression or massage of a TP causes localized pain and may cause referred pain and autonomic phenomena. The authors describe a 58-year-old woman who experienced precipitation of substantial psychological symptoms directly related to her treatment for a lower abdominal TP. Her symptoms resolved after 2 weeks of receiving high-velocity, low-amplitude manipulation and soft tissue massage. Particularly in the abdomen, TPs may be associated with psychological reactions as well as physical aspects of bodily function.

Metamizol Relieves Pain Without Interfering With Cerulein-Induced Acute Pancreatitis in Mice.

OBJECTIVES: Animal models are essential to understand the pathogenesis of acute pancreatitis (AP) and to develop new therapeutic strategies. Although it has been shown that cerulein-induced AP is associated with pain in experimental animals, most experiments are carried out without any pain-relieving treatment because researchers are apprehensive of an interference of the analgetic agent with AP-associated inflammation. In light of the growing ethical concerns and the legal tightening regarding animal welfare during experiments, this attitude should be changed. METHODS: Acute pancreatitis was induced by cerulein in the C57BL/6J and FVB/N mouse inbred strains. One group received vehicle only, and the other was treated with metamizol as analgetic agent. Pain sensation and parameters of AP were analyzed as well as the effect of metamizol in the pancreas and its actions in the brain. RESULTS: We report that oral administration of metamizol protects cerulein-treated mice from abdominal pain without influencing the clinical and histopathological course of the disease. In addition, it could be shown that metamizol reduces the central pain response. CONCLUSIONS: This study reveals that oral administered metamizol has no influence on the cerulein-induced AP and can be given as an analgesic to increase animal welfare in experiments with induced AP.