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Background and Aims: Pain is a cardinal symptom in inflammatory bowel disease [IBD]. An important structure in the transduction of pain signalling is the myenteric plexus [MP]. Nevertheless, IBD-associated infiltration of the MP by immune cells lacks in-depth characterisation. Herein, we decipher intra- and periganglionic immune cell infiltrations in Crohn´s disease [CD] and ulcerative colitis [UC] and provide a comparison with murine models of colitis., Methods: Full wall specimens of surgical colon resections served to examine immune cell populations by either conventional immuno-histochemistry or immunofluorescence followed by either bright field or confocal microscopy. Results were compared with equivalent examinations in various murine models of intestinal inflammation., Results: Whereas the MP morphology was not significantly altered in IBD, we identified intraganglionic IBD-specific B cell- and monocyte-dominant cell infiltrations in CD. In contrast, UC-MPs were infiltrated by CD8+ T cells and revealed a higher extent of ganglionic cell apoptosis. With regard to the murine models of intestinal inflammation, the chronic dextran sulphate sodium [DSS]-induced colitis model reflected CD [and to a lesser extent UC] best, as it also showed increased monocytic infiltration as well as a modest B cell and CD8+ T cell infiltration., Conclusions: In CD, MPs were infiltrated by B cells and monocytes. In UC, mostly CD8+ cytotoxic T cells were found. The chronic DSS-induced colitis in the mouse model reflected best the MP-immune cell infiltrations representative for IBD., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: It is known that various chronic pain conditions lead to maladaptive changes in the central nervous system. Endometriosis is frequently associated with chronic pelvic pain (CPP). Its sufficient treatment remains a clinical challenge. Transcranial direct current stimulation (tDCS) has been shown to be a powerful method to reduce chronic pain. Therefore, this study aimed to investigate pain reduction via anodal tDCS in patients with endometriosis and CPP., Methods: This clinical phase II, placebo-controlled, randomized, parallel-design study included 36 patients with endometriosis and CPP. All patients had CPP, defined as a score of ≥3/10 on the visual analog scale for ≥3 months in the prior 6 months. Anodal or placebo tDCS (18 patients per arm) was applied over the primary motor cortex for 10 days. The primary outcome measure was the pressure pain threshold (objective pain measure), and secondary outcomes were the numerical rating scale score (subjective pain measure), Von Frey monofilaments, and disease- and pain-related questionnaires. Data were collected at baseline, after the 10-day stimulation, and at a follow-up session, which took place 1 week after the tDCS had ended. Statistical analyses were performed with analyses of variance and t tests., Results: Significant decreased pain perception in both pain measurements (pressure pain threshold and numerical rating scale score) was found for the active tDCS group compared with the placebo group. This proof-of-concept study shows that tDCS is a helpful supporting pain therapy for patients with endometriosis and CPP. Moreover, further analyses revealed that 1 week after the stimulation had ended, pain reduction as indexed by pressure pain threshold remained significantly decreased, which indicates possible long-term analgesic effects., Conclusion: The present study provides evidence that tDCS is an effective therapy for pain reduction in endometriosis-associated CPP. The results support the notion that CPP is developed and maintained in the central nervous system, making a multimodal pain therapy necessary., Trial Registration: www.ClinicalTrials.gov ID: NCT05231239., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The paracaspase MALT1 is a crucial regulator of immune responses in various cellular contexts. Recently, there is increasing evidence suggesting that MALT1 might represent a novel key player in mucosal inflammation. However, the molecular mechanisms underlying this process and the targeted cell population remain unclear. In this study, we investigate the role of MALT1 proteolytic activity in the context of mucosal inflammation. We demonstrate a significant enrichment of MALT1 gene and protein expression in colonic epithelial cells of UC patients, as well as in the context of experimental colitis. Mechanistically we demonstrate that MALT1 protease function inhibits ferroptosis, a form of iron-dependent cell death, upstream of NF-κB signaling, which can promote inflammation and tissue damage in IBD. We further show that MALT1 activity contributes to STAT3 signaling, which is essential for the regeneration of the intestinal epithelium after injury. In summary, our data strongly suggests that the protease function of MALT1 plays a critical role in the regulation of immune and inflammatory responses, as well as mucosal healing. Understanding the mechanisms by which MALT1 protease function regulates these processes may offer novel therapeutic targets for the treatment of IBD and other inflammatory diseases., Competing Interests: Authors declare no conflict of interest.

Background: Flow cytometry of intestinal lymphocytes is discussed to be a stronger predictor of enteropathy-associated T-cell lymphoma development in refractory celiac disease than T-cell clonality analysis., Aims: To investigate possible associations between clinical characteristics of refractory celiac disease patients and aberrant intraepithelial lymphocytes and to evaluate the accuracy of immunophenotyping for the identification of high-risk refractory celiac disease., Methods: Flow cytometry of isolated lymphocytes from duodenal biopsies of controls and celiac disease patients was performed and results were compared to clinical data., Results: Flow cytometry analysis was performed on 42 controls, 37 non-complicated celiac disease and 30 refractory celiac disease cases with or without T-cell receptor clonality. Elevated aberrant intraepithelial lymphocyte counts were significantly associated with severe malabsorption. A 15% cut-off (aberrant lymphocytes among all lymphocytes) had the best discriminatory ability to identify high-risk patients. However, this technique failed to identify some high-risk cases (sensitivity 63%, specificity 100%). The severity of malabsorption was added to the criteria for high-risk refractory celiac disease, improving the correct patients' allocation (sensitivity 100%, specificity 96%)., Conclusion: Immunophenotyping of aberrant intraepithelial lymphocytes is a good predictor for high-risk refractory celiac disease. Furthermore, adding the evaluation of malabsorption to the diagnostic assessment of refractory celiac disease optimizes accuracy., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique to modulate cortical excitability and to induce neuronal plasticity. With a wide range of applications in neurological and psychiatric disorders, the efficiency of tDCS is also studied in the treatment of various pain conditions. Treatment with tDCS might accordingly provide pain relief for patients with acute or chronic pain and thus lead to an increase in quality of life. Moreover, applied as an adjunct therapy, tDCS can reduce help to reduce pain medication intake and accompanying adverse events. To this end, this review examines studies evaluating the efficacy of tDCS in pain relief in patients with intra-abdominal pain., Methods: A structured search of the PubMed medical database was carried out to identify possibly relevant studies. Studies were compared in terms of treatment characteristics, general conditions, and results. Jadad scale was applied for quality analyses., Results: Out of 289 articles that were found initially, 6 studies were identified that met eligibility criteria. Five out of 6 studies reported significant effects for pain reduction in different types of intra-abdominal pain., Conclusions: Results indicate that tDCS might be able to reduce intra-abdominal pain. However, more randomized-controlled trials with larger sample size are necessary to define clinically relevant effects as well as treatment characteristics such as duration of stimulation.