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PURPOSE: Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery. METHODS: In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1. RESULTS: All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; P=0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; P=0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups. CONCLUSION: For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100052085).

Background and Aims: The endocannabinoid (eCB) system includes ligands (anandamide and 2‐arachidonoyl glycerol, 2‐AG), receptors and catabolizing enzymes (fatty acid amide hydrolase, FAAH and monoacylglycerol lipase) expressed in both the brain and gut. We investigated whether the FAAH inhibitor, URB597, influenced visceral pain to colorectal distension (CRD) in an acute stress‐related model of visceral hypersensitivity induced by the selective corticotropin‐releasing factor receptor subtype 1 (CRF1) agonist, cortagine. Methods: Male Sprague–Dawley rats were injected subcutaneously (SC) with URB597 (3 mg/kg) or vehicle and 2 h later, intraperitoneally with cortagine (10 μg/kg) or vehicle. The visceromotor responses (VMR) were assessed to a first CRD (baseline) before injections, and to a second CRD 15 min after the last treatment. Brain, jejunum, and proximal colon were collected from treated and naïve rats for levels quantification of three fatty acid amides (FAAs) [anandamide (arachidonyl‐ethanolamide, AEA), oleoyl‐ethanolamide (OEA) and palmitoyl‐ethanolamide (PEA)], and 2‐AG. In separate animals, defecation/diarrhea were monitored after URB597 and cortagine. Key Results: URB597 inhibited cortagine‐induced increased VMR at 40 mmHg (89.0 ± 14.8% vs. 132.5 ± 15.6% for vehicle SC, p < 0.05) and 60 mmHg (107.5 ± 16.1% vs. 176.9 ± 24.4% for vehicle SC, p < 0.001) while not influencing basal VMR. In URB597 plus cortagine group, FAAs levels increased in the brain and intestinal tissue while 2‐AG did not change. URB597 did not modify cortagine‐induced defecation/diarrhea versus vehicle. Conclusions and Inferences: URB597 shows efficacy to elevate brain and intestinal FAAs and to counteract the colonic hypersensitivity induced by peripheral activation of CRF1 signaling supporting a potential strategy of FAAH inhibitors to alleviate stress‐related visceral hypersensitivity. [ABSTRACT FROM AUTHOR]

Background: An impaired intestinal barrier with the activation of corticotropin‐releasing factor (CRF), Toll‐like receptor 4 (TLR4), and proinflammatory cytokine signaling, resulting in visceral hypersensitivity, is a crucial aspect of irritable bowel syndrome (IBS). The gut exhibits abundant expression of neurotensin; however, its role in the pathophysiology of IBS remains uncertain. This study aimed to clarify the effects of PD149163, a specific agonist for neurotensin receptor 1 (NTR1), on visceral sensation and gut barrier in rat IBS models. Methods: The visceral pain threshold in response to colonic balloon distention was electrophysiologically determined by monitoring abdominal muscle contractions, while colonic permeability was measured by quantifying absorbed Evans blue in colonic tissue in vivo in adult male Sprague–Dawley rats. We employed the rat IBS models, i.e., lipopolysaccharide (LPS)‐ and CRF‐induced visceral hypersensitivity and colonic hyperpermeability, and explored the effects of PD149163. Key Results: Intraperitoneal PD149163 (160, 240, 320 μg kg−1) prevented LPS (1 mg kg−1, subcutaneously)‐induced visceral hypersensitivity and colonic hyperpermeability dose‐dependently. It also prevented the gastrointestinal changes induced by CRF (50 μg kg−1, intraperitoneally). Peripheral atropine, bicuculline (a GABAA receptor antagonist), sulpiride (a dopamine D2 receptor antagonist), astressin2‐B (a CRF receptor subtype 2 [CRF2] antagonist), and intracisternal SB‐334867 (an orexin 1 receptor antagonist) reversed these effects of PD149163 in the LPS model. Conclusions and Inferences: PD149163 demonstrated an improvement in visceral hypersensitivity and colonic hyperpermeability in rat IBS models through the dopamine D2, GABAA, orexin, CRF2, and cholinergic pathways. Activation of NTR1 may modulate these gastrointestinal changes, helping to alleviate IBS symptoms. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The erector spinae plane block (ESPB) and quadratus lumborum block (QLB) are two novel interfascial plane block techniques with possible analgesic effects for both incisional and visceral pain. However, the results of the intercomparison of the two techniques for analgesia after abdominal surgery remain controversial.A systematic literature search was performed on five databases for randomized controlled trials comparing the analgesic efficacy of ESPB and QLB in abdominal surgery. The primary outcome was the 24 h postoperative intravenous IV morphine‐equivalent consumption. A meta‐analysis was performed using a random‐effects model, with subgroup analyses based on the types of surgery and approaches of QLB.The 24 h postoperative IV morphine‐equivalent consumption was lower in patients receiving ESPB than in those receiving QLB (MD –2.307 mg; 95% CI ‒4.577 to −0.038; p = 0.046; and I2 = 96.5%), though the reduction did not reach clinically meaningful difference. Static and dynamic pain at different postoperative time points, the time to first rescue analgesia, and the incidence of PONV showed no significant difference between the two groups. However, the QLB group demonstrated a significantly prolonged time in performing the block compared to the ESPB group (MD –2.985 min; 95% CI –4.608 to –1.363; p < 0.001; and I2 = 97.5%).Based on the available evidence from a systematic search of databases, the single‐shot ESPB exhibits similar analgesic effects as QLB in abdominal surgery. The incidence of PONV was similar between the two techniques, with no block‐related complications identified though QLB might be a more technically challenging approach than ESPB. [ABSTRACT FROM AUTHOR]

Visceral and somatic pain serve as protective mechanisms against external threats. Accumulated evidence has confirmed that the paraventricular hypothalamus (PVH) plays an important role in the perception of visceral and somatic pain, whereas the exact neural pathways and molecules distinguishing them remain unclear. Here, we report distinct neuronal ensembles within the PVH dedicated to processing visceral and somatic pain signals. An essential discovery is the distinct expression of P2X3R and VIPR2 in visceral and somatic pain-activated PVH neuronal ensembles. Furthermore, visceral pain- and somatic pain-responsive PVH neuronal ensembles project to specific downstream regions, the ventral part of the lateral septal nucleus (LSV) and the caudal part of the zona incerta (ZIC), respectively. These findings unveil that the PVH acts as a pain sorting center that distinctly processes visceral and somatic pain, identifying potential molecular targets for specific pain processing and providing a new framework for comprehending how the brain processes nociceptive information. [Display omitted] • Distinct PVH neural ensembles specifically respond to visceral and somatic pain • Visceral and somatic pain-labeled PVH neurons display unique transcription profiles • Visceral and somatic pain-labeled PVH neurons exhibit distinct projection patterns • PVHP2X3R+-LSV and PVHVIPR2+-ZIC circuits separately modulate visceral and somatic pain Li et al. identify the paraventricular hypothalamus (PVH) as a pain sorting center that distinctly processes visceral and somatic pain. PVH neural ensembles activated by visceral and somatic pain exhibit unique transcriptional profiles and projection patterns, thus providing evidence for clinically targeted treatment of visceral and somatic pain. [ABSTRACT FROM AUTHOR]

Background: Despite advances in pain management, cancer-related pain remains a critical issue for many patients. In recent years, there has been a growing interest in the use of fascial plane blocks, such as the Erector Spinae Plane Block (ESPB), for managing chronic pain, including in the oncology field. We conducted a systematic review to synthetize existing evidence on the use of ESPB for cancer pain management. Methods: We selected studies published between January 2016 to April 2024. A systematic search in Pubmed and Embase databases was performed. The search strategy included the following keywords and/or MeSH terms according to the controlled vocabulary of the databases sought: ((erector spinae plane block) OR (ESP block) OR (ESPB) AND ((cancer pain). We considered eligible Randomized, nonrandomized studies, case series and case reports reporting data on the use of ESPB in patients with cancer pain. Results: The search revealed 34 studies. Among these, we found one RCT, three retrospective studies, two case series, and 28 case reports for a total of 135 patients. Studies included described the use of ESPB for the management of various types of cancer pain across different conditions, including chronic thoracic cancer-related pain, abdominal visceral pain and pain related to bone metastases. Single-shot ESPB was performed in 26 studies while continuous ESPB and the use of a peripheral nerve catheter for continuous analgesia were described in 8 studies. Neurolytic ESPB was performed in 6 studies for a total of 10 patients There was a high clinical heterogeneity in terms of technique, drugs, and use of adjuvants. The lack of comparators was a major flaw, together with the low level of evidence in the majority of the included studies. Conclusions: The evidence supporting the use of ESPB for cancer pain management is currently scarce, heterogeneous, and of low quality. To better understand its potential and provide robust clinical guidance, future research needs to focus on rigorous comparative studies, standardization of techniques and larger sample sizes. [ABSTRACT FROM AUTHOR]

Gastric pain has limited treatment options and the mechanisms within the central circuitry remain largely unclear. This study investigates the central circuitry in gastric pain induced by noxious gastric distension (GD) in mice. Here, we identified that the nucleus tractus solitarius (NTS) serves as the first-level center of gastric pain, primarily via the vagus nerve. The prelimbic cortex (PL) is engaged in the perception of gastric pain. The lateral parabrachial nucleus (LPB) and the paraventricular thalamic nucleus (PVT) are crucial regions for synaptic transmission from the NTS to the PL. The glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuitry is necessary and sufficient for the processing of gastric pain. Overall, our finding reveals a glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuitry that transmits gastric nociceptive signaling by the vagus nerve in mice. It provides an insight into the gastric pain ascending pathway and offers potential therapeutic targets for relieving visceral pain. Gastric pain has limited treatment options and the nociceptive ascending pathway remains largely unclear. Here, the authors identify a glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuit that provides a basis for the clinical treatment of gastric pain. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects of different electrical stimulation methods (bilateral electroacupuncture (BEA), unilateral EA (UEA), transcutaneous electrical acustimulation (TEA, stimulation via surface electrodes placed at acupoints), and sacral nerve stimulation (SNS)) on visceral pain in a rodent model of irritable bowel syndrome (IBS). Ten-day-old male and female pups were treated with 0.2 ml of 0.5% acetic acid (AA) solution. Visceral sensitivity was assessed using an electromyogram (EMG) in response to graded colorectal distension. In the first experiment, bilateral EA at ST36 acupoint was performed with different parameters in male rats to determine the best stimulation parameters. In the second experiment, male rats were randomly assigned into the Sham, BEA, UEA, TEA, and SNS groups to determine the best stimulation method. Lastly, the AA-treated female rats were randomly assigned into the BEA and sham groups to investigate a potential treatment difference between the sexes. Two distinct sets of stimulation parameters were used: Set 1 (100 Hz, 0.5 ms pulse width, 0.1 s ON, 0.4 s OFF, 0.4–3.0 mA current) and Set 2 (25 Hz, 0.5 ms pulse width, 2 s ON, 3 s OFF, 0.4–3.0 mA current). Results (1) The parameter set of 100Hz was found to be most effective in reducing visceral pain. (2) Both acute UEA and TEA effectively relieved visceral pain, whereas acute SNS did not exhibit such an effect. (3) Acute BEA improved visceral pain in both male and female rats. Conclusions These findings suggest that transcutaneous ST36 stimulation is as effective as direct ST36 stimulation and unilateral ST36 stimulation is comparable to bilateral stimulation. Development of a novel therapy using unilateral transcutaneous ST36 stimulation is warranted. [ABSTRACT FROM AUTHOR]

Introduction: Visceral pain represents the most common digestive issue, frequently resulting from long-term inflammation, such as inflammatory bowel diseases. The lack of effective drugs prompted search of new therapeutic approaches. In this regard, gamma-aminobutyric acid (GABA) and Melissa officinalis (Mo) appear as excellent candidates as they were recognized to have several positive effects on the digestive system. The aim of this research was to evaluate the effects of a compound containing GABA and Mo (GABA-Mo 5:1) in inflammation-induced intestinal damage and visceral pain. Methods: Colitis was induced in rats by intrarectal 2,4-dinitrobenzenesulfonic acid (DNBS) administration. DNBS-treated animals received GABA-Mo (80 mg/kg BID), starting 3 days before DNBS administration, until 14 days after colitis induction (preventive protocol), or starting 7 days after DNBS until day 21 (curative protocol). Visceral pain was assessed by measuring the viscero-motor response (VMR) and the abdominal withdrawal reflex (AWR) to colorectal distension on day 7, 14 (both protocols) and 21 (curative protocol) after DNBS administration. Results: In the preventive protocol, GABA-Mo reduced AWR at day 14 but had no effect on VMR. In the spinal cord, treatment with GABA-Mo significantly prevented microglia reactivity (Iba-1 positive cells). In the colon, the supplement significantly decreased malondialdehyde (MDA, index of oxidative stress) and IL-1β levels and counteracted the decreased expression of claudin-1. Moreover, GABA-Mo normalized the increased levels of plasma lipopolysaccharide binding protein (LBP, index of altered intestinal permeability). In the curative protocol, GABA-Mo significantly counteracted visceral hypersensitivity persistence in DNBS-treated animals (day 14 and 21). In the spinal cord, GABA-Mo significantly reduced GFAP positive cell density (astrocytes). Histological evaluations highlighted a mild but significant effect of GABA-Mo in promoting healing from DNBS-induced colon damage. Colonic MDA and myeloperoxidase (index of leukocyte infiltration) levels were reduced, while the decreased colonic claudin-1 expression was normalized. In addition, the increased levels of plasma LBP were normalized by GABA-Mo administration. Discussion: In conclusion GABA-Mo, particularly in the curative protocol, was able to reduce visceral pain and intestinal inflammation, likely through a reinforcement of intestinal barrier integrity, thus representing a suitable approach for the management of abdominal pain, especially in the remission stages of colitis. [ABSTRACT FROM AUTHOR]

Visceral hypersensitivity, a hallmark of disorders of the gut‐brain axis, is associated with exposure to early‐life stress (ELS). Activation of neuronal β3‐adrenoceptors (AR) has been shown to alter central and peripheral levels of tryptophan and reduce visceral hypersensitivity. In this study, we aimed to determine the potential of a β3‐AR agonist in reducing ELS‐induced visceral hypersensitivity and possible underlying mechanisms. Here, ELS was induced using the maternal separation (MS) model, where Sprague Dawley rat pups were separated from their mother in early life (postnatal day 2–12). Visceral hypersensitivity was confirmed in adult offspring using colorectal distension (CRD). CL‐316243, a β3‐AR agonist, was administered to determine anti‐nociceptive effects against CRD. Distension‐induced enteric neuronal activation as well as colonic secretomotor function were assessed. Tryptophan metabolism was determined both centrally and peripherally. For the first time, we showed that CL‐316243 significantly ameliorated MS‐induced visceral hypersensitivity. Furthermore, MS altered plasma tryptophan metabolism and colonic adrenergic tone, while CL‐316243 reduced both central and peripheral levels of tryptophan and affected secretomotor activity in the presence of tetrodotoxin. This study supports the beneficial role of CL‐316243 in reducing ELS‐induced visceral hypersensitivity, and suggests that targeting the β3‐AR can significantly influence gut‐brain axis activity through modulation of enteric neuronal activation, tryptophan metabolism, and colonic secretomotor activity which may synergistically contribute to offsetting the effects of ELS. [ABSTRACT FROM AUTHOR]

One of the most common concerns of patients undergoing surgery is preoperative anxiety, with a prevalence of up to 48%. The effects of preoperative anxiety continue beyond the preoperative period and are associated with more severe postoperative pain and poorer treatment outcomes. Treatment options for preoperative anxiety are often limited as sedatives cause side effects and their efficacy remains controversial. Placebo research has shown that optimization of positive treatment expectations, as can be achieved through placebo administration and education, has clinically relevant effects on preoperative anxiety, pain and treatment outcomes. As the administration of masked placebos raises ethical questions, clinical studies have increasingly focused on the use of open, non-deceptive placebo administration (open-label placebo, OLP). The use of OLPs to reduce preoperative anxiety and modify clinically relevant postoperative outcomes has not yet been investigated. This bicentric, prospective, randomized-controlled clinical trial (PATE Trial; German Registry for Clinical Studies DRKS00033221), an associated project of the Collaborative Research Center (CRC) 289 “Treatment Expectation”, aims to alleviate preoperative anxiety by optimizing positive treatment expectations facilitated by OLP. Furthermore, this study examines a potential enhancement of these effects through aspects of observational learning, operationalized by a positive expectation-enhancing video. In addition, patient’s perspective on the self-efficacy and appropriateness of OLPs prior to surgery will be assessed. To achieve these objectives, female patients will be randomized into three groups before undergoing gynecological laparoscopic surgery. One group receives the OLP with a positive rationale conveyed by a study physician. A second group receives the same intervention, OLP administration and rationale provided by a physician, and additionally watches a video on OLP presenting a satisfied patient. A third group receives standard treatment as usual (TAU). Outcome measures will be effects on preoperative anxiety and postoperative experience, particularly visceral and somatic postoperative pain. As the non-deceptive administration of placebos; when indicated; may yield positive outcomes without side effects, and as current treatment of preoperative anxiety is limited, evidence from clinical placebo research has the potential to improve outcomes and patient experience in the surgical setting. [ABSTRACT FROM AUTHOR]

Neuronal ensemble activity entrained by local field potential (LFP) patterns underlies a variety of brain functions, including emotion, cognition, and pain perception. Recent advances in machine learning approaches may enable more effective methods for analyzing LFP patterns across multiple brain areas than conventional time-frequency analysis. In this study, we tested the performance of two machine learning algorithms, AlexNet and the Transformer models, to classify LFP patterns in eight pain-related brain regions before and during acetic acid-induced visceral pain behaviors. Over short time windows lasting several seconds, applying AlexNet to LFP power datasets, but not to raw time-series LFP traces from multiple brain areas, successfully achieved superior classification performance compared with simple LFP power analysis. Furthermore, applying the Transformer directly to the raw LFP traces achieved significantly superior classification performance than AlexNet when using LFP power datasets. These results demonstrate the utility of the Transformer in the analysis of neurophysiological signals, and pave the way for its future applications in the decoding of more complex neuronal activity patterns. [ABSTRACT FROM AUTHOR]

Bloating is a feeling of abdominal fullness and discomfort; abdominal distension is increasing in abdominal girth. Abdominal bloating is among the most commonly reported and bothersome gastrointestinal symptoms and could be associated with many disorders such as irritable bowel syndrome. According to the Rome IV criteria, the prevalence of functional bloating is 3.5 % (after exclusion of other disorders of the gut-brain interaction) but is much higher when associated with irritable bowel syndrome (up to 80%). The pathophysiology of functional bloating is multifactorial and includes among others constipation, pelvic floor dysfunction, visceral hypersensitivity, abdomino-phrenic dyssynergia, and carbohydrates intolerance. The treatments target the main mechanisms and include diet, medication and biofeedback. Transit disorders can be treated respectively by secretagogues and rifaximin but are not available in France. Biofeedback is useful in case of pelvic floor dysfunction and abdomino-phrenic dyssynergia. Low FODMAP diet is useful in patients with food-related bloating and distension but need to be proposed in selected patients. Neuromodulators help to decrease the sensation of bloating and the viscero-somatic reflex associated with abdominal distension. Both of them are available in France. Probiotics and antibiotics targeting small intestinal bacterial overgrowth cannot be recommended in this indication. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the frequency dependence of electroacupuncture (EA) in alleviating chronic visceral pain in patients with irritable bowel syndrome (IBS) and the differences in the gut microbiota and metabolites as potential mechanisms to explain frequency dependence. Methods: A visceral hyperalgesia model was established by colorectal instillation of 2,4,6‐trinitrobenzene sulfonic acid in rats, and EA treatment at 2/10 Hz, 2/50 Hz and 2/100 Hz was applied at ST25. Visceral sensation was quantified by the abdominal withdrawal reflex score and the area under the curve of the rectus abdominis electromyogram in response to colorectal distension. Ultrastructural morphological damage of colonic tissue of the rats was examined by transmission electron microscopy. 16S rRNA gene sequencing and 1H‐nuclear magnetic resonance spectroscopy were applied to study the differences in the gut microbiota and to perform metabonomic profiling of the colonic tissue. Key Results: EA at ST25 at different frequencies attenuated chronic visceral pain, ultrastructural morphological damage to colonic tissue and disruption of the gut microbiota in IBS rats. The frequency of 2/100 Hz has more regulatory pathways than 2/10 Hz and 2/50 Hz. In addition, IBS rats exhibited colonic metabolic disorders, and pantothenate was significantly upregulated after EA treatment at different frequencies. Very low‐density lipoprotein and 2‐hydroxybutyrate were significantly increased in the 2/10 Hz group, while low density lipoprotein, very low‐density lipoprotein, 2‐hydroxybutyrate, methylmalonate and alpha‐hydroxyisobutyric acid were significantly increased in the 2/100 Hz group. Conclusions and Inferences: EA at ST25 at different frequencies attenuated chronic visceral pain through different gut microbiota and metabolic pathways. [ABSTRACT FROM AUTHOR]

Chitin–glucan (CG) is a new generation of prebiotic. Lactobacillus acidophilus NCFM® (NCFM) is a probiotic with the ability to decrease abdominal pain. We evaluate the functional and molecular gastrointestinal responses to a synbiotic administration combining CG and NCFM in a rat model of long-lasting colon hypersensitivity. The intracolonic pressure was assessed during the 9-week experiment in animals receiving CG in association or not with NCFM and compared to that in Lacticaseibacillus paracasei Lpc-37®-treated animals and control rats receiving tap water. The effects of the synbiotic were evaluated using the Wallace score, the quantification of colon myeloperoxidase (MPO) and the master genes driving analgesia and inflammation. CG 1.5 alone and NCFM 109 colony forming units (CFU) alone similarly decreased the visceral pain sensitivity. Lpc-37 had no significant effect. The best profile of pain perception inhibition was obtained with the combination of CG 1.5 g and NCFM 109 CFU, confirming a synbiotic property. This synbiotic treatment significantly reduced macroscopic colonic lesions and MPO concentrations, and induced master genes involved in analgesia (CB1, CB2, MOR, PPARα), with a downregulation of inflammatory cytokines (IL-1β, TNFα) and an induction of IL-10 and PPARγ. In conclusion, CG 1.5 g + NCFM 109 CFU significantly decreased visceral pain perception and intestinal inflammation through the regulation of master genes. [ABSTRACT FROM AUTHOR]

Abstract The purpose of this study was to investigate the effects of different electrical stimulation methods (bilateral electroacupuncture (BEA), unilateral EA (UEA), transcutaneous electrical acustimulation (TEA, stimulation via surface electrodes placed at acupoints), and sacral nerve stimulation (SNS)) on visceral pain in a rodent model of irritable bowel syndrome (IBS). Ten-day-old male and female pups were treated with 0.2 ml of 0.5% acetic acid (AA) solution. Visceral sensitivity was assessed using an electromyogram (EMG) in response to graded colorectal distension. In the first experiment, bilateral EA at ST36 acupoint was performed with different parameters in male rats to determine the best stimulation parameters. In the second experiment, male rats were randomly assigned into the Sham, BEA, UEA, TEA, and SNS groups to determine the best stimulation method. Lastly, the AA-treated female rats were randomly assigned into the BEA and sham groups to investigate a potential treatment difference between the sexes. Two distinct sets of stimulation parameters were used: Set 1 (100 Hz, 0.5 ms pulse width, 0.1 s ON, 0.4 s OFF, 0.4–3.0 mA current) and Set 2 (25 Hz, 0.5 ms pulse width, 2 s ON, 3 s OFF, 0.4–3.0 mA current). Results (1) The parameter set of 100Hz was found to be most effective in reducing visceral pain. (2) Both acute UEA and TEA effectively relieved visceral pain, whereas acute SNS did not exhibit such an effect. (3) Acute BEA improved visceral pain in both male and female rats. Conclusions These findings suggest that transcutaneous ST36 stimulation is as effective as direct ST36 stimulation and unilateral ST36 stimulation is comparable to bilateral stimulation. Development of a novel therapy using unilateral transcutaneous ST36 stimulation is warranted.

Abstract Neuronal ensemble activity entrained by local field potential (LFP) patterns underlies a variety of brain functions, including emotion, cognition, and pain perception. Recent advances in machine learning approaches may enable more effective methods for analyzing LFP patterns across multiple brain areas than conventional time-frequency analysis. In this study, we tested the performance of two machine learning algorithms, AlexNet and the Transformer models, to classify LFP patterns in eight pain-related brain regions before and during acetic acid-induced visceral pain behaviors. Over short time windows lasting several seconds, applying AlexNet to LFP power datasets, but not to raw time-series LFP traces from multiple brain areas, successfully achieved superior classification performance compared with simple LFP power analysis. Furthermore, applying the Transformer directly to the raw LFP traces achieved significantly superior classification performance than AlexNet when using LFP power datasets. These results demonstrate the utility of the Transformer in the analysis of neurophysiological signals, and pave the way for its future applications in the decoding of more complex neuronal activity patterns.

This study aimed to A) evaluate changes in pain and function following an outpatient interdisciplinary pain management program (IPMP) for children with different chronic pain conditions and B) explore differences in pain and function at baseline and discharge for different diagnoses.A retrospective chart review was performed for 488 children who participated in an outpatient IPMP. Children’s pain and physical, social, and emotional functioning were assessed at initial evaluation, discharge, and one-to-two-month follow-up. Patients were stratified by diagnosis (complex regional pain syndrome [CRPS], headache, musculoskeletal pain, visceral pain, and widespread pain) to evaluate differences in pain and functioning at baseline and discharge.Children’s pain and function improved from initial evaluation to discharge. Those with headache and musculoskeletal pain exhibited better baseline physical and emotional functioning than other diagnostic groups (p = 0.03; p = 0.005; p = 0.002; p = 0.04). Children with CRPS displayed the worst baseline physical functioning (p = 0.003). Those with widespread pain exhibited the worst baseline emotional functioning at both initial evaluation and discharge (p = 0.009; p = 0.007).Children with CRPS, visceral pain, and widespread pain undergoing treatment in an IPMP exhibited the most impaired baseline functioning, while those with musculoskeletal pain and headache were least impaired. All exhibited improvements in pain and function following the IPMP. [ABSTRACT FROM AUTHOR]

Testosterone (T) and 17β-estradiol (E2 ) are produced in male and female humans and are potent metabolic regulators in both sexes. When E2 and T production stops or decreases during aging, metabolic dysfunction develops and promotes degenerative metabolic and vascular disease. Here, we discuss the shared benefits afforded by E2 and T for metabolic function human females and males. In females, E2 is central to bone and vascular health, subcutaneous adipose tissue distribution, skeletal muscle insulin sensitivity, antiinflammatory immune function, and mitochondrial health. However, T also plays a role in female skeletal, vascular, and metabolic health. In males, T’s conversion to E2 is fundamental to bone and vascular health, as well as prevention of excess visceral adiposity and the promotion of insulin sensitivity via activation of the estrogen receptors. However, T and its metabolite dihydrotestosterone also prevent excess visceral adiposity and promote skeletal muscle growth and insulin sensitivity via activation of the androgen receptor. In conclusion, T and E2 are produced in both sexes at sex-specific concentrations and provide similar and potent metabolic benefits. Optimizing levels of both hormones may be beneficial to protect patients from cardiometabolic disease and frailty during aging, which requires further study. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS), which is characterized by chronic abdominal pain, has a high global prevalence. The anterior cingulate cortex (ACC), which is a pivotal region involved in pain processing, should be further investigated regarding its role in the regulation of visceral sensitivity and mental disorders. A C57BL/6J mouse model for IBS was established using chronic acute combining stress (CACS). IBS‐like symptoms were assessed using behavioral tests, intestinal motility measurements, and abdominal withdrawal reflex scores. Fluoro‐Gold retrograde tracing and immunohistochemistry techniques were employed to investigate the projection of ACC gamma‐aminobutyric acid‐producing (GABAergic) neurons to the lateral hypothalamus area (LHA). Chemogenetic approaches enabled the selective activation or inhibition of the ACC–LHA GABAergic pathway. Enzyme‐linked immunosorbent assay (ELISA) and western blot analyses were conducted to determine the expression of histamine, 5‐hydroxytryptamine (5‐HT), and transient receptor potential vanilloid 4 (TRPV4). Our findings suggest that CACS induced IBS‐like symptoms in mice. The GABA type A receptors (GABAAR) within LHA played a regulatory role in modulating IBS‐like symptoms. The chemogenetic activation of ACC–LHA GABAergic neurons elicited anxiety‐like behaviors, intestinal dysfunction, and visceral hypersensitivity in normal mice; however, these effects were effectively reversed by the administration of the GABAAR antagonist Bicuculline. Conversely, the chemogenetic inhibition of ACC–LHA GABAergic neurons alleviated anxiety‐like behaviors, intestinal dysfunction, and visceral hypersensitivity in the mouse model for IBS. These results highlight the crucial involvement of the ACC–LHA GABAergic pathway in modulating anxiety‐like behaviors, intestinal motility alterations, and visceral hypersensitivity, suggesting a potential therapeutic strategy for alleviating IBS‐like symptoms. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a gastrointestinal (GI) disease accompanied by changes in bowel habits without any specific cause. Gintonin is a newly isolated glycoprotein from ginseng that is a lysophosphatidic acid (LPA) receptor ligand. To investigate the efficacy and mechanisms of action of gintonin in IBS, we developed a zymosan-induced IBS murine model. In addition, electrophysiological experiments were conducted to confirm the relevance of various ion channels. In mice, gintonin restored colon length and weight to normal and decreased stool scores, whilst food intake remained constant. Colon mucosal thickness and inflammation-related tumor necrosis factor-α levels were decreased by gintonin, along with a reduction in pain-related behaviors. In addition, the fecal microbiota from gintonin-treated mice had relatively more Lactobacillaceae and Lachnospiraceae and less Bacteroidaceae than microbiota from the control mice. Moreover, gintonin inhibited transient receptor potential vanilloid (TRPV) 1 and TRPV4 associated with visceral hypersensitivity and voltage-gated Na+ 1.5 channels associated with GI function. These results suggest that gintonin may be one of the effective components in the treatment of IBS. [ABSTRACT FROM AUTHOR]

Summary: Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition associated with altered bowel habits and recurrent abdominal pain, often triggered by food intake. Current treatments focus on improving stool pattern, but effective treatments for pain in IBS are still lacking due to our limited understanding of pathophysiological mechanisms. Visceral hypersensitivity (VHS), or abnormal visceral pain perception, underlies abdominal pain development in IBS, and mast cell activation has been shown to play an important role in the development of VHS. Our work recently revealed that abdominal pain in response to food intake is induced by the sensitization of colonic pain‐sensing neurons by histamine produced by activated mast cells following a local IgE response to food. In this review, we summarize the current knowledge on abdominal pain and VHS pathophysiology in IBS, we outline the work leading to the discovery of the role of histamine in abdominal pain, and we introduce antihistamines as a novel treatment option to manage chronic abdominal pain in patients with IBS. [ABSTRACT FROM AUTHOR]

Globally, irritable bowel syndrome (IBS) is present in approximately 10% of the population. While this condition does not pose a risk of complications, it has a substantial impact on the patient's quality of life. Moreover, this disease has a significant financial impact on healthcare systems. This includes the direct costs associated with the diagnosis and treatment of these patients, as well as the indirect costs that arise from work absenteeism and reduced productivity. In light of these data, recent research has focused on elucidating the pathophysiological basis of this condition in order to improve the quality of life for affected individuals. Despite extensive research to date, we still do not fully understand the precise mechanisms underlying IBS. Numerous studies have demonstrated the involvement of the gut–brain axis, visceral hypersensitivity, gastrointestinal dysmotility, gut microbiota dysbiosis, food allergies and intolerances, low-grade mucosal inflammation, genetic factors, and psychosocial factors. The acquisition of new data is crucial for the advancement of optimal therapeutic approaches aimed at enhancing the general health of these patients while simultaneously reducing the financial burden associated with this ailment. [ABSTRACT FROM AUTHOR]

Nowadays, the pharmacological management of visceral hypersensitivity associated with colitis is ineffective. In this context, targeting purinergic P2X4 receptor (P2X4R), which can modulate visceral pain transmission, could represent a promising therapeutic strategy. Herein, we tested the pain-relieving effect of two novel and selective P2X4R antagonists (NC-2600 and NP-1815-PX) in a murine model of DNBS-induced colitis and investigated the mechanisms underlying their effect. Tested drugs and dexamethasone (DEX) were administered orally, two days after colitis induction. Treatment with tested drugs and DEX improved tissue inflammatory parameters (body weight, spleen weight, macroscopic damage, TNF and IL-1β levels) in DNBS-rats. In addition, NC-2600 and NP-1815-PX attenuated visceral pain better than DEX and prevented the reduction of occludin expression. In in vitro studies, treatment of CaCo2 cells with supernatant from THP-1 cells, previously treated with LPS plus ATP, reduced the expression of tight junctions protein. By contrast, CaCo2 cells treated with supernatant from THP-1 cells, previously incubated with tested drugs, counteracted the reduction of tight junctions due to the inhibition of P2X4R/NLRP3/IL-1β axis. In conclusion, these results suggest that the direct and selective inhibition of P2X4R represents a viable approach for the management of visceral pain associated with colitis via NLRP3/IL-1β axis inhibition. [ABSTRACT FROM AUTHOR]

Although anesthesia provides favorable conditions for surgical procedures, recent studies have revealed that the brain remains active in processing noxious signals even during anesthesia. However, whether and how these responses affect the anesthesia effect remains unclear. The ventrolateral periaqueductal gray (vlPAG), a crucial hub for pain regulation, also plays an essential role in controlling general anesthesia. Hence, it was hypothesized that the vlPAG may be involved in the regulation of general anesthesia by noxious stimuli. Here, we found that acute noxious stimuli, including capsaicin-induced inflammatory pain, acetic acid-induced visceral pain, and incision-induced surgical pain, significantly delayed recovery from sevoflurane anesthesia in male mice, whereas this effect was absent in the spared nerve injury-induced chronic pain. Pretreatment with peripheral analgesics could prevent the delayed recovery induced by acute nociception. Furthermore, we found that acute noxious stimuli, induced by the injection of capsaicin under sevoflurane anesthesia, increased c-Fos expression and activity in the GABAergic neurons of the ventrolateral periaqueductal gray. Specific reactivation of capsaicin-activated vlPAGGABA neurons mimicked the effect of capsaicin and its chemogenetic inhibition prevented the delayed recovery from anesthesia induced by capsaicin. Finally, we revealed that the vlPAGGABA neurons regulated the recovery from anesthesia through the inhibition of ventral tegmental area dopaminergic neuronal activity, thus decreasing dopamine (DA) release and activation of DA D1-like receptors in the brain. These findings reveal a novel, cell- and circuit-based mechanism for regulating anesthesia recovery by nociception, and it is important to provide new insights for guiding the management of the anesthesia recovery period. [ABSTRACT FROM AUTHOR]

Headache and visceral pain are common clinical painful conditions, which often co-exist in the same patients. Numbers relative to their co-occurrence suggest possible common pathophysiological mechanisms. The aim of the present narrative review is to describe the most frequent headache and visceral pain associations and to discuss the possible underlying mechanisms of the associations and their diagnostic and therapeutic implications based on the most recent evidence from the international literature. The conditions addressed are as follows: visceral pain from the cardiovascular, gastrointestinal, and urogenital areas and primary headache conditions such as migraine and tension-type headache. The most frequent comorbidities involve the following: cardiac ischemic pain and migraine (possible shared mechanism of endothelial dysfunction, oxidative stress, and genetic and hormonal factors), functional gastrointestinal disorders, particularly IBS and both migraine and tension-type headache, primary or secondary dysmenorrhea and migraine, and painful bladder syndrome and headache (possible shared mechanisms of peripheral and central sensitization processes). The data also show that the various visceral pain–headache associations are characterized by more than a simple sum of symptoms from each condition but often involve complex interactions with the frequent enhancement of symptoms from both, which is crucial for diagnostic and treatment purposes. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Exosome‐like nanoparticles (ELNs) have emerged as crucial mediators of intercellular communication, evaluated as potential bioactive nutraceutical biomolecules. We hypothesized that oral ELNs have some therapeutic effect on irritable bowel syndrome (IBS).In our study, ELNs from tea (Camellia sinensis) leaves were extracted by differential centrifugation. We investigated the role of ELNs by assessing visceral hypersensitivity, body weight, bowel habits, tight junctions, and corticotropin‐releasing hormone (CRH) in rats subjected to water avoidance stress (WAS) to mimic IBS with and without ELNs (1 mg/kg per day) for 10 days.The average diameter of ELNs from LCC, FD and MZ tea tree were 165 ± 107, 168 ± 94, and 168 ± 108 nm, the concentration of ELNs were 1.2 × 1013, 1 × 1013, and 1.5 × 1013 particles/mL, respectively. ELNs can be taken up by intestinal epithelial cells. In WAS rats, ELNs significantly restored weight, recovered tight junctions, decreased CRH, and CRH receptor 1 expression levels and inhibited abdominal hypersensitivity in comparison to positive control.Oral tea‐derived ELN improves symptoms of IBS by potentially modulating the CRH pathway. [ABSTRACT FROM AUTHOR]

Background: Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition measurements of skeletal muscle and fat are associated with late‐onset CHCs and nonrelapse mortality after aPBSCT. Methods: Leveraging the Blood or Marrow Transplant Survivor Study, we examined association between pre‐aPBSCT body composition and new‐onset grade 3–5 CHCs among 187 adults with lymphoma treated with aPBSCT (2011–2014) surviving ≥2 years after aPBSCT. Using computed tomography scans at the L3 level, skeletal muscle mass (skeletal muscle area and skeletal muscle density [SMD]) and body fat (subcutaneous adipose tissue and visceral adipose tissue) were measured and quantified as sex‐specific z‐scores. Competing risk models were built to study the impact of body composition on incident grade 3 through 5 CHCs and nonrelapse mortality (NRM) adjusting for confounders. Results: The study cohort had a median age at aPBSCT of 57 years with 63% males, 77% non‐Hispanic Whites and 81% with non‐Hodgkin lymphoma. The 5‐year cumulative incidence of grade 3 through 5 CHCs was 47% (95% Confidence Interval, CI, 38%–56%). Each SD increase in SMD was associated with 30% reduced risk of grade 3 through 5 CHCs (95% CI, 0.50–0.96). The 10‐year cumulative incidence of NRM was 16% (95% CI, 10–22). No body composition measure was associated with NRM. Conclusions: The association between SMD and grade 3 through 5 CHCs following aPBSCT could inform development of prognostic models to identify adults with lymphoma at greatest risk of morbidity following aPBSCT. [ABSTRACT FROM AUTHOR]

The pressing need for safer, more efficacious analgesics is felt worldwide. Preclinical tests in animal models of painful conditions represent one of the earliest checkpoints novel therapeutics must negotiate before consideration for human use. Traditionally, the pain status of laboratory animals has been inferred from evoked nociceptive assays that measure their responses to noxious stimuli. The disconnect between how pain is tested in laboratory animals and how it is experienced by humans may in part explain the shortcomings of current pain medications and highlights a need for refinement. Here, we survey human patients with chronic pain who assert that everyday aspects of life, such as cleaning and leaving the house, are affected by their ongoing level of pain. Accordingly, we test the impact of painful conditions on an ethological behavior of mice, digging. Stable digging behavior was observed over time in naive mice of both sexes. By contrast, deficits in digging were seen after acute knee inflammation. The analgesia conferred by meloxicam and gabapentin was compared in the monosodium iodoacetate knee osteoarthritis model, with meloxicam more effectively ameliorating digging deficits, in line with human patients finding meloxicam more effective. Finally, in a visceral pain model, the decrease in digging behavior correlated with the extent of disease. Ultimately, we make a case for adopting ethological assays, such as digging, in studies of pain in laboratory animals, which we believe to be more representative of the human experience of pain and thus valuable in assessing clinical potential of novel analgesics in animals. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Acupuncture & Tuina Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The transient receptor potential ankyrin 1 (TRPA1) channel plays a pivotal role in the respiratory and gastrointestinal tracts. Within the respiratory system, TRPA1 exhibits diverse distribution patterns across key cell types, including epithelial cells, sensory nerves, and immune cells. Its activation serves as a frontline sensor for inhaled irritants, triggering immediate protective responses, and influencing airway integrity. Furthermore, TRPA1 has been implicated in airway tissue injury, inflammation, and the transition of fibroblasts, thereby posing challenges in conditions, such as severe asthma and fibrosis. In sensory nerves, TRPA1 contributes to nociception, the cough reflex, and bronchoconstriction, highlighting its role in both immediate defense mechanisms and long-term respiratory reflex arcs. In immune cells, TRPA1 may modulate the release of pro-inflammatory mediators, shaping the overall inflammatory landscape. In the gastrointestinal tract, the dynamic expression of TRPA1 in enteric neurons, epithelial cells, and immune cells underscores its multifaceted involvement. It plays a crucial role in gut motility, visceral pain perception, and mucosal defense mechanisms. Dysregulation of TRPA1 in both tracts is associated with various disorders such as asthma, Chronic Obstructive Pulmonary Disease, Irritable Bowel Syndrome, and Inflammatory Bowel Disease. This review emphasizes the potential of TRPA1 as a therapeutic target and discusses the efficacy of TRPA1 antagonists in preclinical studies and their promise for addressing respiratory and gastrointestinal conditions. Understanding the intricate interactions and cross-talk of TRPA1 across different cell types provides insight into its versatile role in maintaining homeostasis in vital physiological systems, offering a foundation for targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Personalized medicine represents a novel and integrative approach that focuses on an individual's genetics and epigenetics, precision medicine, lifestyle and exposures as key players of health status and disease phenotypes. Methods: In this narrative review, we aim to carefully discuss the current knowledge on gender disparities in cardiometabolic diseases, and we consider the sex‐ specific expression of miRNAs and their role as promising tool in precision medicine. Results: Personalised medicine overcomes the restricted care of patient based on a binomial sex approach, by enriching itself with a holistic and dynamic gender integration. Recognized as a major worldwide health emergency, cardiometabolic disorders continue to rise, impacting on health systems and requiring more effective and targeted strategies. Several sex and gender drivers might affect the onset and progression of cardiometabolic disorders in males and females at multiple levels. In this respect, distinct contribution of genetic and epigenetic mechanisms, molecular and physiological pathways, sex hormones, visceral fat and subcutaneous fat and lifestyle lead to differences in disease burden and outcomes in males and females. Conclusions: Sex and gender play a pivotal role in precision medicine because the influence the physiology of each individual and the way they interact with environment from intrauterine life. [ABSTRACT FROM AUTHOR]

Empathetic relationships and the social transference of behaviours have been shown to occur in humans, and more recently through the development of rodent models, where both fear and pain phenotypes develop in observer animals. Clinically, observing traumatic events can induce 'trauma and stressor‐related disorders' as defined in the DSM 5. These disorders are often comorbid with pain and gastrointestinal disturbances; however, our understanding of how gastrointestinal – or visceral – pain can be vicariously transmitted is lacking. Visceral pain originates from the internal organs, and despite its widespread prevalence, remains poorly understood. We established an observation paradigm to assess the impact of witnessing visceral pain. We utilised colorectal distension (CRD) to induce visceral pain behaviours in a stimulus rodent while the observer rodent observed. Twenty four hours post‐observation, the observer rodent's visceral sensitivity was assessed using CRD. The observer rodents were found to have significant hyperalgesia as determined by lower visceral pain threshold and higher number of total pain behaviours compared with controls. The behaviours of the observer animals during the observation were found to be correlated with the behaviours of the stimulus animal employed. We found that observer animals had hypoactivity of the hypothalamic–pituitary–adrenal (HPA) axis, highlighted by reduced corticosterone at 90 minutes post‐CRD. Using c‐Fos immunohistochemistry we showed that observer animals also had increased activation of the anterior cingulate cortex, and decreased activation of the paraventricular nucleus, compared with controls. These results suggest that witnessing another animal in pain produces a behavioural phenotype and impacts the brain–gut axis. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Using transcriptomic profiling combined with physiological and genetic dissection of nociceptor signalling, we identify angiotensin II as a putative mediator of nociception in colitis. Visceral pain is a leading cause of morbidity in inflammatory bowel disease (IBD), contributing significantly to reduced quality of life. Currently available analgesics often lack efficacy or have intolerable side effects, driving the need for a more complete understanding of the mechanisms causing pain. Whole transcriptome gene expression analysis was performed by bulk RNA sequencing of colonic biopsies from patients with ulcerative colitis (UC) and Crohn's disease (CD) reporting abdominal pain and compared with noninflamed control biopsies. Potential pronociceptive mediators were identified based on gene upregulation in IBD biopsy tissue and cognate receptor expression in murine colonic sensory neurons. Pronociceptive activity of identified mediators was assessed in assays of sensory neuron and colonic afferent activity. RNA sequencing analysis highlighted a 7.6-fold increase in the expression of angiotensinogen transcripts, Agt , which encode the precursor to angiotensin II (Ang II), in samples from UC patients (P = 3.2 × 10−8). Consistent with the marked expression of the angiotensin AT1 receptor in colonic sensory neurons, Ang II elicited an increase in intracellular Ca2+ in capsaicin-sensitive, voltage-gated sodium channel subtype NaV1.8-positive sensory neurons. Ang II also evoked action potential discharge in high-threshold colonic nociceptors. These effects were inhibited by the AT1 receptor antagonist valsartan. Findings from our study identify AT1 receptor-mediated colonic nociceptor activation as a novel pathway of visceral nociception in patients with UC. This work highlights the potential utility of angiotensin receptor blockers, such as valsartan, as treatments for pain in IBD. [ABSTRACT FROM AUTHOR]

Pain is an uncomfortable sensation triggered by the nervous system in response to tissue damage or other body damage. It can be dull, achy, shooting, burning, orpins-and-needles. Pain is tied to emotional, psychological, and cognitive factors and can be categorized into acute, chronic, referred, cancer, neuropathic, and visceral pain. Acute pain is experienced rapidly in response to disease or injury, while chronic pain lasts more than three months. Referred pain originates in one part of the body but is felt in another. Cancer pain is caused by nerve irritation caused by malignancy, neuropathic pain is caused by damage to the nervous system, and visceral pain is caused by problems with internal organs. Symptoms may include depression, flu-like symptoms, in ability to concentrate, muscle spasms, sleep disturbances, and un expected weight loss. Serious symptoms may indicate a life-threatening condition, such as a heart attack. Pain can be caused by a variety of diseases, disorders, and conditions, including inflammatory syndromes, malignancy, trauma, and infection. [ABSTRACT FROM AUTHOR]

Disorders of the gut-brain interaction (DGBIs) are presently classified into mutually exclusive anatomical area-related symptom-based categories according to the Rome IV criteria. The pathophysiology of visceral nociception, which contributes to the wide range of symptoms of DGBIs, involves complex psychobiological processes arising from the bidirectional interactions of multiple systems at the gut and brain levels, which affect symptom expression and illness behaviors. The attitude toward an illness and expression of pain and bowel habit vary across cultures with variable interpretation based on sociocultural beliefs, which may not tally with the medical definitions. Thus, psychological factors impact DGBI definitions, their severity and health care utilization. Due to the poor localization and multisegment referral of visceral pain, the anatomical site of pain may not correspond to the affected segment, and there may be a variable degree of overlap among symptoms. The somewhat restrictively defined Rome IV criteria assume one-to-one correlation of symptoms with underlying pathophysiology and ignore overlapping DGBIs, nonstandardized symptom categories, and change or shift in category over time. The microorganic nature of DGBIs resulting from systemic, metabolic or motility disorders, gut dysbiosis and inflammation are not addressed in the Rome IV criteria. Although there is a multidimensional clinical profile that does address these factors, it is not followed rigorously in practice. Threshold changes for diagnostic criteria or addition/deletion of symptoms leads to wide variation among different DGBI criteria resulting in uncertain comparability of results. Although the Rome IV criteria are excellent for research studies and therapeutic trials in homogenous populations, further improvement is needed for their wider applicability in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of fecal microbiota transplantation regulating the PAR2-TRPV1 pathway on visceral hypersensitivity, mast cell activation, and gut microbiota in a rat model of irritable bowel syndrome. Methods: Rats were randomly divided into Control group, IBS group, FMT group, and FMT+SLIGRL-NH2 group. Measurement of fecal water content, colorectal distension (CRD) and behavioral observation to evaluate visceral sensitivity, detection of colon mast cell (MC) activity using toluidine blue staining, 16S rDNA sequencing of gut microbiota, and protein blotting to detect the expression of PAR2, TRPV1, SP, and CGRP proteins in colon tissue. Results: The results showed that the AWR score, number of MCs, and expression of PAR2, TRPV1, SP, and CGRP proteins in colon tissue of rats in the IBS group were significantly higher than those in the Control group, while the number of OTUs, Chao1, and Shannon index were significantly lower than those in the Control group(P<0.05); The AWR score, number of MCs, and protein expression of PAR2, TRPV1, SP, and CGRP in colon tissue of FMT group rats were significantly lower than those of IBS group, while the number of OTUs, Chao1, and Shannon index were significantly higher than those of IBS group (P<0.05); Compared with the FMT group, the FMT+SLIGRL-NH2 group showed a significant increase in AWR score, number of MCs, and expression of PAR2, TRPV1, SP, and CGRP proteins in colon tissue, while the number of OTUs, Chao1, and Shannon index decreased significantly (P<0.05). Compared with the Control group, the relative abundance of Firmicutes, Bacteroidetes, and Lactobacillus in the IBS group decreased significantly, while the relative abundance of Spirochetes, Proteobacteria and Prevotella increased significantly (P<0.05); Compared with the IBS group, the relative abundance of Firmicutes, Bacteroidetes, and Lactobacillus in the FMT group significantly increased, while the relative abundance of Spirochetes, Proteobacteria, and Prevotella decreased significantly (P<0.05); Compared with the FMT group, the relative abundance of Firmicutes, Bacteroidetes, and Lactobacillus in the FMT+SLIGRL-NH2 group decreased significantly, while the relative abundance of Spirochetes, Proteobacteria, and Prevotella increased significantly (P<0.05). Conclusion: Fecal microbiota transplantation can inhibit visceral hypersensitivity and mast cell activation in IBS rats, regulate intestinal microbiota balance, and its mechanism of action may be related to the inhibition of PAR2-TRPV1 signaling pathway activation. [ABSTRACT FROM AUTHOR]

Copyright of Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas is the property of Universidad de Santiago de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Despite achieving endoscopic remission, over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain. Visceral pain and the microbiome exhibit sex-dependent interactions, while visceral pain in IBD shows a sex bias. Our aim was to evaluate whether post-inflammatory microbial perturbations contribute to visceral hypersensitivity in a sex-dependent manner.Methods Males, cycling females, ovariectomized, and sham-operated females were given dextran sodium sulfate to induce colitis and allowed to recover. Germ-free recipients received sex-appropriate and cross-sex fecal microbial transplants (FMT) from post-inflammatory donor mice. Visceral sensitivity was assessed by recording visceromotor responses to colorectal distention. The composition of the microbiota was evaluated via 16S rRNA gene V4 amplicon sequencing, while the metabolome was assessed using targeted (short chain fatty acids – SCFA) and semi-targeted mass spectrometry.Results Post-inflammatory cycling females developed visceral hyperalgesia when compared to males. This effect was reversed by ovariectomy. Both post-inflammatory males and females exhibited increased SCFA-producing species, but only males had elevated fecal SCFA content. FMT from post-inflammatory females transferred visceral hyperalgesia to both males and females, while FMT from post-inflammatory males could only transfer visceral hyperalgesia to males.Conclusions Female sex, hormonal status as well as the gut microbiota play a role in pain modulation. Our data highlight the importance of considering biological sex in the evaluation of visceral pain.

Background: Alterations in gut-brain axis communication pathways and the gut microbiota ecosystem caused by early life stress have been extensively described as critical players in the pathophysiology of stress-induced disorders. However, the extent to which stress-induced gut microbiota alterations manifest in early life and contribute to the sex-specific susceptibility to distinct gut-brain phenotypes in adulthood has yet to be defined. Methods: Male and female Sprague-Dawley rat offspring underwent maternal separation (3h/day from postnatal day 2–12). Faecal samples were collected before weaning for gut microbiota 16S rRNA sequencing and metabolomic analysis. Visceral pain sensitivity and negative valence behaviours were assessed in adulthood using colorectal distension and the forced swim test respectively. Behavioural data were processed in a two-step cluster analysis to identify groupings within the dataset. Multi-omics analysis was carried out to investigate if the microbial signatures following early life stress were already defined according to the membership of the adult behavioural phenotypes. Results: Maternal separation resulted in increased visceral hypersensitivity while showing a trend for a sex-dependent increase in negative valence behaviour in adulthood. The cluster analysis revealed four clusters within the dataset representing distinct pathophysiological domains reminiscent of the behavioural consequences of early-life stress: 1. resilient, 2. pain, 3. immobile and 4. comorbid. The early life gut microbiota of each of these clusters show distinct alterations in terms of diversity, genus level differential abundance, and functional modules. Multi-omic integrations points towards a role for different metabolic pathways underlying each cluster-specific phenotype. Conclusion: Our study is the first to identify distinct phenotypes defined by susceptibility or resilience to gut-brain dysfunction induced by early life stress. The gut microbiota in early life shows sex-dependent alterations in each cluster that precede specific behavioural phenotypes in adulthood. Future research is warranted to determine the causal relationship between early-life stress-induced changes in the gut microbiota and to understand the trajectory leading to the manifestation of different behavioural phenotypes in adulthood.