ObjectiveSlipping rib syndrome is an underrecognized condition characterized by hypermobility of the false ribs (ribs 8-10), resulting in pain throughout the abdominal and pelvic regions. This study aimed to describe genitopelvic pain disorders and related experiences among individuals with slipping rib syndrome.MethodsAn exploratory, descriptive, cross-sectional survey was distributed using convenience sampling from July 2024 to November 2024. Sociodemographic characteristics, diagnostic timelines, and the Patient Global Impression of Change were used to assess the self-reported efficacy of pelvic floor physical therapy for genitopelvic pain disorders among individuals with slipping rib syndrome.ResultsSeventy-nine individuals with slipping rib syndrome participated; most were women (92.2%) and White (96.9%), and the mean age was 33.4 years. The average diagnostic delay was 5.4 years, and frequent misdiagnoses included costochondritis, anxiety, and gastrointestinal conditions. More than half (54.4%) had Ehlers-Danlos syndrome, predominantly the hypermobile subtype (81.1%). More than 50% reported moderate to severe impacts of slipping rib syndrome on sexual activity, and 26.9% attributed their vulvar or pelvic pain directly to the condition. Common comorbidities included hypertonic pelvic floor, chronic pelvic pain syndrome, endometriosis, vaginismus, interstitial cystitis, and pudendal neuralgia. Among participants who received pelvic floor physical therapy for genitopelvic pain disorders and symptoms, the mean Patient Global Impression of Change score was 4.5, indicating no change to minimal improvement, and 18.2% reported worsening symptoms. Diaphragmatic breathing similarly resulted in no improvement or worsening of symptoms in many participants.ConclusionsThis study is the first to explore the potential impact of slipping rib syndrome on sexual activity and its possible contribution to genitopelvic pain disorders. Symptom overlap with gynecologic conditions complicates diagnosis and management. These findings underscore the importance of evaluating for slipping rib syndrome during pelvic health assessments, particularly in patients with persistent or unexplained pelvic and abdominal pain. Further research is needed to clarify the musculoskeletal mechanisms underlying pelvic pain and to guide interdisciplinary care for individuals with slipping rib syndrome.

Hunner-type interstitial cystitis (HIC) is an inflammatory subtype of interstitial cystitis/bladder pain syndrome marked by persistent urothelial injury and bladder dysfunction. Bisphenol A (BPA) can disturb redox and inflammatory homeostasis, but its relevance to HIC-associated urothelial vulnerability remains unclear. This study examined whether acyl-CoA synthetase long-chain family member 4 (ACSL4) contributes to BPA-associated ferro-aging-like urothelial injury. Among non-pregnant adult women, higher creatinine-corrected urinary BPA was associated with a phenotype predominantly characterized by urgency urinary incontinence (UUI), and the primary Mendelian randomization analysis suggested higher interstitial cystitis (IC) risk with genetically proxied BPA exposure. Integrated transcriptomic, BPA-target, and machine-learning analyses prioritized ACSL4 as a consistent HIC-associated candidate. HIC tissues showed higher ferro-aging-like transcriptional scores and ACSL4 expression; single-cell analyses further identified disease-associated urothelial cell-state remodeling, with higher ACSL4 expression and SenePy scores in HIC urothelial cells. Structure-based modeling suggested a plausible BPA-ACSL4 interaction, while cellular thermal shift assay (CETSA) indicated BPA-associated thermal stabilization of ACSL4. In primary human urothelial cells, BPA increased ACSL4 mRNA and protein expression, lipid peroxidation, iron accumulation, p21 expression, senescence-associated β-galactosidase (SA-β-Gal) positivity, inflammatory signaling, and barrier impairment, together with reduced Lamin B1 and ZO-1 expression and transepithelial electrical resistance (TEER). ACSL4 silencing and vitamin C attenuated these changes. In mice, PRGL493 and vitamin C each attenuated multiple BPA-induced bladder abnormalities. Together, these findings support an ACSL4-associated ferro-aging-like urothelial injury phenotype involving iron-lipid stress, senescence-associated changes, inflammation, and barrier impairment, with relevance to selected features of HIC.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is biologically heterogeneous. No single bladder-directed therapy addresses every relevant mechanism. Recent reviews have covered pathophysiology, multimodal care, and biomaterial-based mucosal repair in detail. This review takes a different route and uses therapeutic migration as a translational lens. The concept refers to moving a treatment idea from another specialty into IC/BPS when the same biological problem appears to be active in a bladder endotype. Representative migrations include platelet-rich plasma and cell-based repair strategies, along with neural, immune-directed, and microbiome approaches. We also discuss one unsuccessful migration. The central question is whether the biological rationale still holds in the bladder. We therefore propose a migration filter that considers mechanism conservation, endotype enrichment, feasibility in the urinary environment, safety, and objective target engagement. Urothelial healing is discussed as a tissue-recovery construct for bladder-centered phenotypes, while treat-to-target principles are adapted for mechanism-informed research. Therapeutic migration remains the overarching framework, but symptom control and biological recovery are treated as separate outcomes.

Dimethyl sulfoxide (DMSO) is a polar aprotic solvent used in biomedical research, pharmaceutical formulation, some clinical applications, and cryopreservation. Here we review molecular activity related to DMSO and selected clinical applications including interstitial cystitis/bladder pain syndrome (IC/BPS), musculoskeletal and traumatic injury, central nervous system (CNS) trauma, cardiovascular and ischemic injury, historical oncology research, local applications, cryopreservation and safety. Of the applications discussed, intravesical DMSO has the clearest contemporary clinical support in selected patients with IC/BPS, particularly those with Hunner-type disease, although its role in non-Hunner disease remains uncertain. This concentration may partly reflect DMSO's limited regulatory approval for therapeutic use, rather than comparative evaluation across indications. Mixed findings have been reported for other applications: modest pain relief has been observed in knee osteoarthritis, whereas no benefit has been found in systemic sclerosis ulcers, where substantial skin intolerance has also been reported. Small uncontrolled clinical series reported reductions in intracranial pressure following intravenous DMSO administration. Walker's monograph separately described neurological recovery after CNS trauma, but concurrent treatment and incomplete documentation limit causal attribution. Reduced intracranial pressure alone does not establish long-term neurological benefit. Historical oncology reports described DMSO-containing hematoxylin preparations, including "haematoxylon", but evidence of antitumor efficacy remains insufficient. Historical ocular and otic applications involved diverse formulations but limited controlled clinical assessment. Cardiovascular protection remains supported mainly by preclinical research. DMSO is an effective cryoprotectant but residual exposure may cause infusion reactions and removal after thaw adds to the processing burden and potential cell loss. Biological activity and risk vary with concentration, route, duration, formulation, material quality, and biological setting. Historical narratives identify questions for further study but do not establish clinical efficacy. This review summarizes reported DMSO effects and risks, examines study limitations, and identifies unresolved research questions.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory disorder characterized by urothelial barrier disruption, neurogenic inflammation, and persistent pelvic pain. However, the upstream molecular mechanisms linking epithelial dysfunction with inflammatory and vascular alterations remain incompletely understood. In this study, we investigated the involvement of STING-associated signaling in experimental cystitis and evaluated the therapeutic potential of the anti-inflammatory marine-derived briareane diterpenoid excavatolide B (EXCB) and its derivative EXCB79 in a cyclophosphamide (CYP)-induced rat model. CYP-induced cystitis was accompanied by increased immunoreactivity of STING together with elevated TBK1 and NF-κB immunostaining, urothelial barrier disruption, CD11b[+] myeloid cell infiltration, increased expression of the inflammatory mediators COX-2 and IL-1β, angiogenesis-associated changes, and enhanced pelvic hypersensitivity. At the concentrations selected for subsequent analyses, EXCB (20 µg/mL) and EXCB79 (5 µg/mL) attenuated pelvic hypersensitivity and were associated with reduced bladder inflammation and partial preservation of epithelial barrier integrity. Double immunofluorescence analysis demonstrated altered spatial associations between STING and CD11b, CD31, VEGF, ZO-1, E-cadherin, and vimentin following CYP administration. Pharmacological modulation of STING-associated signaling was accompanied by reduced immunoreactivity of STING-associated markers together with attenuation of inflammatory, vascular, and epithelial barrier-related alterations, including reduced VEGF immunoreactivity. Collectively, these findings support an association between STING-associated signaling and inflammatory, vascular, and epithelial alterations in experimental cystitis and suggest that pharmacological modulation of this pathway may represent a potential therapeutic strategy for bladder inflammation and pain-related symptoms.

Interstitial cystitis and bladder pain syndrome are clinically overlapping conditions that should be distinguished according to Hunner lesion status. IC with Hunner lesions is a distinct inflammatory bladder disease characterized by urothelial denudation, lymphoplasmacytic infiltration, adaptive immune activation, and progressive structural impairment. The intensity and distribution of these inflammatory and structural abnormalities may vary among patients with IC, but the underlying pathological pattern is comparatively coherent. BPS without Hunner lesions is substantially more heterogeneous. Urothelial barrier dysfunction, mast cell and sensory nerve signaling, pelvic floor dysfunction, peripheral sensitization, and central or nociplastic pain mechanisms may contribute to symptoms in different combinations. Candidate urine and blood-based biomarkers, including cytokines, chemokines, neurotrophic factors, immune cell indices, and multiomics signatures, may support phenotyping, assessment of disease activity, or prediction of treatment response. However, most remain exploratory because their intended clinical use, analytical standardization, diagnostic thresholds, and external validity have not been established. This narrative review compares the clinical and histopathological features of IC and BPS, evaluates the evidence for proposed immune and neuroregulatory mechanisms, examines the translational status of candidate biomarkers, and discusses disease-specific and phenotype-guided management. These findings support a primary distinction between IC and BPS. Additional phenotyping is useful after this distinction to characterize heterogeneity within BPS and clinically relevant coexisting mechanisms.

or mzyjp23@nottingham.ac.uk Body Protective Compound-157 (BPC-157) is a synthetic pentadecapeptide popular among athletic populations for musculoskeletal injury recovery, despite lacking regulatory approval for human use and evidence being largely limited to animal models. This PRISMA-compliant systematic review, prospectively registered with PROSPERO (CRD420261406325), aimed to evaluate the efficacy and safety of BPC-157 for orthopaedic and regenerative purposes in humans. Electronic databases (Embase, PubMed, Cochrane Library and ClinicalTrials.gov) were searched up to 1 June 2026. Eligibility included quantitative and qualitative studies investigating BPC-157 for any indication in human participants. Methodological quality and certainty of evidence was assessed using the National Institutes of Health Quality Assessment Tool for Before-After Studies With No Control Group and GRADE framework respectively. Findings were narratively synthesised in accordance with SWiM guidance. Three studies (n=30) met the inclusion criteria, consisting of a retrospective study of intra-articular BPC-157 injections for knee pain (n=16), a retrospective pilot study of intravesical BPC-157 for interstitial cystitis (n=12), and a prospective pilot study evaluating intravenous BPC-157 safety (n=2). All studies reported symptom improvement in most participants without treatment-related adverse events, but were judged to be of poor methodological quality. Overall certainty of evidence was rated very low due to serious risk of bias, indirectness and imprecision. Accordingly, BPC-157 should not be used clinically in humans outside ethically approved, regulated, high-quality clinical trials.

Pentosan polysulfate sodium (PPS) remains an oral treatment option for selected patients with bladder pain syndrome, but recognition of PPS-associated pigmentary maculopathy has created uncertainty about long-term prescribing. The central clinical problem is that reported retinal-risk estimates vary markedly between studies.

Urinary tract infections (UTIs) are a major risk factor for interstitial cystitis/bladder pain syndrome (IC/BPS), yet the mechanisms driving chronic pelvic pain and associated symptoms remain poorly understood. Here, we investigated the role of microglia and Toll-like receptor 4 (TLR4) in a mouse model of post-UTI chronic pelvic pain (PUPP). Infection with E. coli induced persistent pelvic allodynia that was significantly attenuated by microglial depletion (PLX5622) or inhibition (minocycline), indicating a key role for microglia in pain maintenance. In contrast, microglial depletion did not improve urinary dysfunction or anxiety- and depression-like behaviors. Prefrontal cortex microglia of PUPP mice exhibited reduced microglial branching complexity and a less ramified phenotype, indicative of an activated microglial state. Transcriptomic profiling of brain CD11b+ cells revealed a reactive microglial signature enriched for chemokines, NFΚB-related genes, and immediate early response genes, alongside pathways involved in immune regulation and leukocyte recruitment. Both general and microglia-specific TLR4 deletion reduced pelvic allodynia and reduced microglial morphological features of activation. Consistent with this, pharmacological TLR4 inhibition in vitro suppressed LPS-induced NFΚB activation, cytokine secretion, and CD68 expression. Together, these findings identify microglial TLR4 as a critical mediator of post-UTI chronic pelvic pain.

BackgroundChronic pelvic pain (CPP) affects an estimated 6-27% of women and is associated with substantial impairment in quality of life (QoL). Common conditions include endometriosis, vulvodynia, and interstitial cystitis. Management typically involves multiple biomedical and psychological strategies, often used in combination, yet their independent associations with QoL and pain interference remain unclear.ObjectivesTo examine associations between six pain management strategies (surgery, hormonal medication, non-hormonal medications/therapies, analgesia, alternative therapies, and psychological therapy) and World Health Organization Quality of Life (WHOQOL-BREF) domains, and pain interference in women with CPP.DesignCross-sectional survey study.MethodsWomen with CPP (N = 147) completed an online questionnaire. Outcomes included WHOQOL-BREF Physical, Psychological, Social, and Environment domains, global QoL, and pain interference. Multiple linear regression models examined associations with QoL domains and pain interference, adjusting for simultaneous strategy use. Ordinal logistic regression examined global quality of life.ResultsSurgery was associated with lower Physical QoL (p = .007). Analgesia was associated with poorer Physical (p = .033), Psychological (p = .022), and Environmental quality of life (p = .041). Psychological therapy was associated with higher Psychological (p = .037) and Environment QoL (p = .023). Use of non-hormonal medications/therapies was associated with greater pain interference (p = .016). No clear associations were observed for Social QoL or global QoL.ConclusionOverall patterns are consistent with a biopsychosocial understanding of CPP. Surgery and analgesia were associated with lower QoL in selected domains, which may reflect greater symptom severity, treatment complexity, or confounding by indication. Psychological therapy was associated with higher psychological and environmental QoL while non-hormonal medications/therapies suggested greater pain interference. Findings suggest earlier integration of psychological care, regular review of analgesic use, and routine monitoring of quality of life and pain interference within multidisciplinary CPP pathways. Causal inferences are limited by the cross-sectional design.