Genetic analyses in humans and macaques followed by cellular and mouse studies demonstrate NPSR1 as a nonhormonal drug target in endometriosis.

Vorspann: Die sowjetischen Kriegsgefangenen stellen nach den Juden die zweitgrößte Opfergruppe nationalsozialistischer Vernichtungspolitik dar. Die Gesamtzahl der sowjetischen Soldaten in deutscher Hand und die genaue Zahl der Opfer sind jedoch noch immer nicht bekannt. Auf der Grundlage neu erschlossener personenbezogener Quellen und langjähriger Studien gelingt es den Autoren, für den Zuständigkeitsbereich des OKW exakte Zahlen zu ermitteln und nachzuweisen, dass immerhin 2,8 Millionen sowjetischer Kriegsgefangener individuell registriert worden sind, so dass sich deren Schicksal genauer nachvollziehen lässt.

The use of Botulinum Neurotoxin A (BoNT/A) to treat peripheral neuropathic pain from nerve injury has garnered interest for its long-lasting effects and safety. This study examined the effects of IncobotulinumtoxinA (Inco/A), a BoNT/A variant without accessory proteins, on nerve regeneration in rats using the chronic constriction injury (CCI) model. Inco/A was administered perineurally at two time points: on days 0 and 21 post CCI. Functional and histological assessments were conducted to evaluate the effect of Inco/A on nerve regeneration. Sciatic Functional Index (SFI) measurements and Compound Muscle Action Potential (CMAP) recordings were conducted at different time points following CCI. Inco/A-treated animals exhibited a 65% improved SFI and 22% reduction in CMAP onset latencies compared to the vehicle-treated group, suggesting accelerated functional nerve recovery. Tissue analysis revealed enhanced remyelination in Inco/A-treated animals and 60% reduction in CGRP and double S100β signal expression compared to controls. Strikingly, 30% reduced immune cell influx into the injury site was observed following Inco/A treatment, suggesting that its anti-inflammatory effect contributes to nerve regeneration. These findings show that two injections of Inco/A promote functional recovery by enhancing neuroregeneration and modulating inflammatory processes, supporting the hypothesis that Inco/A has a neuroprotective and restorative role in nerve injury conditions.

Dyspareunia, or pain during sex, is a common and often debilitating symptom in individuals with endometriosis and/or interstitial cystitis/bladder pain syndrome (IC/BPS). Despite its significant impact on quality of life, it is frequently overlooked in research. This review evaluates how dyspareunia has been addressed in preclinical investigations of these conditions. A systematic search was conducted using Embase from 1998 to 2021, identifying original in vivo preclinical studies using female rodents to model (i) endometriosis and (ii) IC/BPS. The search aimed to identify studies that assessed dyspareunia. Study quality and risk of bias were evaluated using a modified CAMARADES checklist. Our analysis found 1,286 studies modelling endometriosis and 674 modelling IC/BPS, but only 18 and 1, respectively, measured dyspareunia. The most common method involved vaginal distention in rats, assessed by either behavioural escape responses or visceromotor reflexes of abdominal muscles. Despite the high prevalence of dyspareunia in these conditions, it is rarely measured in preclinical studies. We identify a significant gap in the literature and offer succinct recommendations for future translational research to address this important symptom. Lay summary: Dyspareunia describes pain occurring before, during or after sexual intercourse. This poorly understood symptom is particularly common in people suffering from two chronic pain-related conditions: endometriosis and IC/BPS, severely impacting their quality of life. Therefore, effective treatments addressing painful sex in people with these conditions are needed. To see the benefits of medical research at the patient’s bedside, it is important to build from basic science research to preclinical animal studies then to human studies. Our study aims to assess the work that has been done so far at the ‘preclinical’ stage. Developments have been made in the methodology used to investigate this symptom in animals, and a summary of all the key findings may help build a platform to design future studies. Given the urgent need to develop new therapeutic strategies, attention given to painful sex by scientific medical researchers and physicians needs to improve.

Chronic pelvic pain (CPP) is a common and burdensome symptom in women yet current clinical management frequently leaves many with persistent pain. The Translational Research in Pelvic Pain (TRiPP) project adopts a pain-focused strategy, aiming to better phenotype CPP through multimodal assessment. Here, we integrated questionnaire, physiological, and biological data to (1) determine whether perturbations in the function of pain-relevant systems in women with CPP can be demonstrated and (2) explore whether these data can stratify women with CPP into meaningful subgroups, independent of diagnostic group. Participants included 108 women, aged 18 to 50 years, with CPP including endometriosis-associated pain (EAP), bladder pain syndrome (BPS), comorbid EAP and BPS, and pelvic pain with no underlying pathology alongside 50 pain-free controls. Analyses were conducted in 3 stages: (1) group comparisons, (2) latent profile analysis to identify CPP subgroups, and (3) clinical characterization of resulting clusters. Compared with controls, CPP participants reported significantly greater fatigue, poorer sleep, higher anxiety, depression, pain catastrophising, and more childhood trauma ( P < 0.01). However, no significant differences were observed in physiological measures. Latent profile analysis revealed 3 distinct CPP subgroups, differentiated by questionnaires rather than physiological measures. Cluster 1 represents a group with predominantly higher-impact pain compared with others, that may be associated with nociplastic mechanisms. These findings support alternative approaches to stratification of CPP separate from standard diagnostic groupings. The role of questionnaire measures in this stratification facilitates translation to clinical settings; however, further work is required to determine whether differing therapeutic approaches are appropriate for each cluster.