Search Results (217)

Background: Pain is a prominent and disabling manifestation of inflammatory bowel disease (IBD), including abdominal, pelvic, musculoskeletal, axial, and neuropathic pain phenotypes. Patients referred to pain clinics represent a selected subgroup with clinically meaningful, persistent, refractory, or diagnostically complex pain. Objective: To characterize pain phenotypes, treatment patterns, interventional pain-care exposure, and utilization burden among patients with IBD evaluated in tertiary pain-clinic settings and to explore differences between Crohn’s disease and ulcerative colitis patients. Methods: We performed a retrospective electronic medical-record cohort study of patients with documented IBD who were evaluated in pain-clinic settings between 24 October 2010 and 14 May 2026. Repeated clinical entries were aggregated into unique visit dates and patient-level variables. IBD diagnosis, pain phenotypes, treatment documentation, interventional procedures, and pain-clinic utilization were summarized descriptively using counts, percentages, means, medians, interquartile ranges, and ranges as appropriate. Crohn’s disease and ulcerative colitis subgroups were compared using univariable odds ratios with 95% confidence intervals and two-sided p-values. Because repeated clinical entries could belong to the same patient, the primary analytic unit was the patient rather than the individual note. Results: The source dataset included 19,615 clinical entries representing 7053 unique pain-clinic visits among 596 unique patients with IBD. The cohort included 314 patients with Crohn’s disease (52.7%), 247 with ulcerative colitis (41.4%), and 35 with IBD-unclassified (5.9%). The mean number of pain-clinic visits per patient was 11.8, with a median of four visits (interquartile range, 1–11). The dominant patient-level pain phenotypes were limb or peripheral joint pain (395/596, 66.3%), back or axial spine pain (358/596, 60.1%), and abdominal or pelvic pain (246/596, 41.3%). Overall, 437 patients (73.3%) had documentation of at least one interventional pain procedure. Compared with ulcerative colitis, Crohn’s disease was associated with higher documentation of abdominal or pelvic pain (148/314, 47.1% vs. 82/247, 33.2%; odds ratio, 1.79; 95% confidence interval, 1.27–2.53; p = 0.001) and fibromyalgia-like or widespread pain (83/314, 26.4% vs. 39/247, 15.8%; odds ratio, 1.92; 95% confidence interval, 1.25–2.93; p = 0.0027). In contrast, radiofrequency procedures (59/314, 18.8% vs. 78/247, 31.6%; odds ratio, 0.50; 95% confidence interval, 0.34–0.74; p = 0.0005) and facet or medial branch procedures (79/314, 25.2% vs. 87/247, 35.2%; odds ratio, 0.62; 95% confidence interval, 0.43–0.89; p = 0.012) were less frequently documented in Crohn’s disease than in ulcerative colitis. Conclusions: Among patients with IBD referred to tertiary pain-clinic evaluation, pain was heterogeneous and predominantly musculoskeletal, axial, neuropathic, and procedurally targetable rather than exclusively visceral. These findings support structured, mechanism-based pain assessment integrated with gastroenterology, rheumatology, and pain-medicine care. Full article

Background: Acute intermittent porphyria (AIP) is the most common and severe form of acute hepatic porphyria, caused by heterozygous mutations in the HMBS gene. Due to its non-specific clinical manifestations and low clinical awareness among clinicians, AIP is frequently misdiagnosed, leading to significant diagnostic delays and potentially fatal complications. Case presentation: We report a 20-year-old female patient who presented with a 9-month history of recurrent abdominal pain, paralytic ileus, unexplained liver injury, and hyponatremia, followed by progressive limb weakness. She was initially misdiagnosed with Guillain–Barré syndrome (GBS) and received intravenous immunoglobulin and systemic glucocorticoids. However, her condition deteriorated, and she developed life-threatening respiratory muscle paralysis requiring invasive mechanical ventilation. The diagnosis of AIP was confirmed by positive urinary porphobilinogen (PBG) testing and identification of the heterozygous HMBS c.517C>T pathogenic variant. The patient was treated with high-dose carbohydrate loading therapy and comprehensive supportive care, resulting in gradual clinical improvement. Discussion and Conclusions: This case exemplifies the substantial diagnostic challenges associated with AIP, especially when it manifests with peripheral neuropathy that closely mimics GBS. The triad of absent albuminocytologic dissociation in cerebrospinal fluid, preceding visceral symptoms, and inadequate response to standard first-line GBS therapy should immediately raise clinical suspicion for AIP. Enhanced clinical awareness of this rare disorder and timely implementation of urinary PBG screening are of paramount importance to prevent irreversible neurological complications and optimize long-term patient outcomes. Full article

Visceral pain is a central feature of chronic gastrointestinal disorders, yet the epithelial sensory mechanisms that shape afferent input before it enters pain-relevant neural pathways remain insufficiently integrated into current models. This review advances the concept that the intestinal epithelium is not only a barrier or endocrine interface, but also an active neuroepithelial regulatory layer positioned upstream of visceral sensory signaling. Neuropod-cell studies established that specialized epithelial cells can communicate rapidly with vagal neurons and preserve luminal stimulus identity through transmitter-selective coding. Enterochromaffin cells extend this framework as polymodal epithelial sensory transducers that detect chemical, microbial, neurohumoral, and mechanical cues, convert them into serotonergic afferent signaling, and can causally amplify visceral hypersensitivity in experimental models. Complementing these amplifying pathways, GUCY2C^high (guanylate cyclase C-enriched) neuropod-like epithelial cells reveal a pain-restraining mechanism that regulates dorsal root ganglion excitability and preserves linaclotide-responsive suppression of nociceptive output in preclinical systems. Together, these findings support an integrative model in which epithelial sensory circuits may act as filters of biological meaning, amplifiers of afferent gain, and brakes on aberrant nociceptive escalation. This framework does not replace neural, immune, or central mechanisms of visceral pain, but adds an upstream epithelial tier that may shape pain vulnerability, persistence, or treatment responsiveness in selected contexts. Defining the cellular logic, molecular mediators, and human relevance of these circuits will be essential for advancing neuroepithelial pain biology toward disease-relevant and therapeutic applications. Full article

Perioperative lidocaine is widely used in horses with acute abdomen for its analgesic, prokinetic, anti-inflammatory, and anti-endotoxic effects, although evidence of its visceral analgesic efficacy remains inconclusive. Given the potential of alternative routes of administration for local anaesthetics, this prospective, randomised, unblinded clinical trial evaluated whether intraperitoneal (IP) lidocaine improves early postoperative recovery, including recovery from anaesthesia and the first 24 h after laparotomy for colic. A Multifactorial Numerical Rating Composite Pain Scale for equines was used for pain assessment. Covariates including aetiology, times of surgery, anaesthesia and recovery, and eventual postoperative constant rate infusion (CRI) of lidocaine were further analysed. Fifty-four horses were enrolled and equally distributed between two groups differing from the IP administration of 2 mg/kg lidocaine (group L) or not (group C) at the end of laparotomy. Postoperative lidocaine CRI (p = 0.007), higher ASA status (p = 0.005), longer recovery time (p = 0.0012), and large intestinal disease compared with small intestinal disease (p = 0.006) were significantly associated with higher pain scores, particularly within the first 24 h. No horse showed signs of toxicity. Although group L demonstrated a trend toward faster pain reduction, IP lidocaine did not significantly improve early postoperative pain outcomes. Postoperative ‘lidocaine CRI’ was associated with more severe cases, questioning its analgesic efficacy. Further research is warranted to optimise safe and effective protocols. Full article

Background: Segmental arterial mediolysis (SAM) is a non-inflammatory vasculopathy that primarily affects the abdominal visceral arteries leading to hemorrhage, ischemia, or pseudoaneurysms. Its presentation can be mimicked by other vasculopathies including vasculitis involving the medium-sized blood vessels making it difficult to diagnose. Case Presentation: A 55-year-old woman presented with a two-hour history of sudden-onset, severe epigastric pain radiating to the chest. She was noted to be hypotensive with low hemoglobin 8.8 g/dL suspicious for a hemorrhagic cause. Her case was complicated by elevated international normalized ratio 3.7 in the setting of warfarin therapy for the mechanical mitral valve. The remainder of her complete blood count, complete metabolic panel, inflammatory markers, autoantibody serologies, and infectious testing were negative. Abdominal computed tomography angiogram revealed hemoperitoneum, bilateral renal infarctions, a large mesenteric hematoma, aneurysmal disease of the common hepatic and inferior mesenteric arteries, thrombosis and proximal dissection of the superior mesenteric artery, acute thrombosis of the left external iliac vein, and multiple sites of arterial extravasation from the pancreaticoduodenal artery and its branches. Mesenteric artery angiogram showed multivessel visceral artery aneurysms and stenoses characteristic of SAM for which she underwent transcatheter arterial embolization of the bleeding vascular bed. We provide a narrative literature review with a focus on common presentations and differentiating characteristics of vasculopathies that can involve medium-sized blood vessels. It is important to accurately diagnose SAM and its potential mimics as management strategies differ. Conclusions: SAM presents with medium vessel vasculopathy without vasculitis. Differentiation from mimics can be difficult but aided by familiarity of their characteristic findings and differentiating clinical characteristics. Full article

Background/Objectives: Cancer-related pain remains one of the most prevalent and distressing symptoms across the disease trajectory, significantly impairing function and quality of life. Although opioids are central to managing moderate to severe pain, their limitations, including adverse effects, dependence risk, and societal concerns, highlight the need for more individualized and comprehensive strategies. This review aims to synthesize current approaches to cancer pain management within a palliative care framework, emphasizing multimodal, mechanism-based, and patient-centered care. Methods: A narrative review was conducted using literature searches of PubMed, Scopus, and Google Scholar. Articles published between 2010 and 2026, with emphasis on recent literature (2020–2026), were included. Search terms included combinations of “cancer pain,” “palliative care,” “multimodal analgesia,” “opioids,” “adjuvant analgesics,” and “neuropathic pain.” Peer-reviewed studies, clinical guidelines, systematic reviews, and meta-analyses relevant to cancer pain mechanisms and management were considered. Results: Cancer pain is heterogeneous, arising from tumor progression and treatment-related injury, and includes neuropathic, visceral, and somatic components. Effective management requires mechanism-based assessment and multimodal strategies. Adjuvant analgesics, such as antidepressants, anticonvulsants, corticosteroids, and topical agents, enhance pain control and reduce opioid reliance. Non-pharmacological interventions and early integration of palliative care further improve symptom management and quality of life. Emerging therapies, including cannabinoid-based treatments and gene-targeted approaches, show promise but require further clinical validation. Conclusions: A multidisciplinary, patient-centered approach that integrates pharmacologic and non-pharmacologic strategies is essential for optimizing cancer pain management. Advancing toward personalized and multimodal care models may improve outcomes, reduce opioid-related risks, and enhance quality of life for patients with cancer. Full article

The dextran sodium sulfate (DSS) colitis model is the most widely used experimental model of inflammatory bowel disease (IBD) due to its simplicity and versatility, with over 7000 PubMed entries in the last decade and an exponential rise in recent years. Since its initial description in 1985, DSS colitis has been extensively evaluated across species, most notably in mice and rats, and has yielded substantial insights into IBD pathogenesis. However, the model’s multifactorial nature poses a dual challenge: it offers an opportunity but complicates study design, interpretation, and translational relevance. This complexity is worsened by inconsistent reporting, which hampers reproducibility and comparability across studies. The broad use of the DSS-induced colitis model yields numerous insights about the model, which help better understand its complexity, characteristics and limitations. Although DSS colitis is induced locally, inflammation in the colon and gut barrier destruction may also affect other organs (such as the liver and brain) and their metabolism and molecular responses, which, in turn, may interfere with colitis-underlying mechanisms and drug response, and may influence the interpretation of results. These intrinsic (intra-experimental) characteristics of the DSS model are summarised in the paper (colitis, gut–brain axis, gut–liver axis). In addition, the DSS model is heavily influenced by numerous extrinsic (inter-experimental) factors (environmental, microbiological, genetic), which may further complicate the colitis model, the study outcomes, and data interpretation, and these are also discussed in the paper. As science advances and new data accumulate, understanding the intricate interplay among internal mechanisms, external factors, and technical variables becomes increasingly essential for the accurate interpretation of DSS outcomes. This review synthesises the complexity and interdependence of factors shaping the DSS model, emphasising the need for meticulous reporting and consideration of methodological nuances to enhance reproducibility, interpretation, and translational value in DSS colitis research. In addition, the review provides practical guidance through a “traps and tricks” subsection and checklist table designed to provide a framework and practical recommendations to better understand, apply, and interpret DSS model results in the context of broader systemic and methodological considerations. Full article

Background: Hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2 (HER2-negative) metastatic breast cancer (MBC) represents a substantial proportion of breast cancer cases in Saudi Arabia. Despite the established efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, particularly Palbociclib, in randomized control trials, real-world data from local institutions in Saudi Arabia remain limited. Objectives: This study aimed to evaluate progression-free survival (PFS), overall survival (OS), and toxicity profile among HR+, HER2-negative MBC female patients treated with Palbociclib at King Fahad Medical City (KFMC). Methods: A retrospective study was conducted on female patients with HR+/HER2-negative MBC treated with oral palbociclib combined with endocrine therapy (ET) at KFMC between January 2021 and September 2024. Data were collected from electronic health records. Descriptive statistics were conducted using mean for continuous variables and frequency for categorical variables. Survival analyses were conducted using Cox regression, log-rank tests and Kaplan–Meier analysis. Results: A total of 169 female patients with HR+/HER2− MBC were included. In the first-line setting, the median PFS was 20.14 months (95% CI: 14.65–30.49), compared with 11.3 months (95% CI: 7.98–not estimable) in the second-line setting. For OS, the median OS values were 53.1 months (95% CI: 41.2–not estimable) in the first-line group and 23.7 months (95% CI: 18.5–not estimable) in the second-line group. Significant predictors of shorter PFS included age, Body Mass Index (BMI), type of ET, cancer type, line of therapy, family history of cancer, and history of VTE. Visceral metastasis (HR = 3.087; p = 0.0229) and ECOG performance status of 4 (HR = 13.86; p = 0.0156) were associated with significantly shorter OS. The most common hematological adverse events (AEs) were neutropenia (45.6%), followed by anemia (5.9%), leukopenia (5.3%), and back pain (5.3%). Most toxicities were managed with dose reduction, holding treatment, or supportive care. Conclusions: Palbociclib demonstrated favorable survival outcomes and a manageable safety profile, with neutropenia being the most common AE. This study provides region-specific real-world evidence supporting the use of Palbociclib in HR+/HER2− MBC. These findings align with global trial data and highlight the importance of individualized treatment in clinical practice. Full article

Background and Objectives: Visceral artery aneurysms (VAAs) are rare but potentially catastrophic vascular abnormalities, particularly in pregnant patients or women of childbearing age. Rupture is often fatal for both mother and fetus, with mortality rates exceeding 70% in some series. While most VAAs are found incidentally, a subset may present acutely with nonspecific abdominal or flank pain, making early recognition and appropriate referral essential. This review article aims to provide General Practitioners (GPs) and emergency department (ED) clinicians with a practical approach to the recognition, investigation, initial management, and escalation pathways for VAAs. Results: Physiological and hormonal adaptations in pregnancy heighten aneurysm rupture risk. Despite this, imaging is frequently delayed. Computed tomography angiography (CTA) remains the gold standard for diagnosis and is safe in pregnancy when clinically justified, with fetal radiation exposure well below teratogenic thresholds. Guidelines from major vascular societies uniformly recommend repairing VAAs in pregnancy or women planning pregnancy irrespective of aneurysm size, and treating pseudoaneurysms urgently in all patients. Endovascular intervention is first-line where anatomy permits, while open or hybrid approaches remain essential in unstable presentations. The manuscript outlines practical steps for ED and GP settings, including haemodynamic stabilization, early obstetric involvement, transfer considerations for rural environments, reproductive counselling, and post-repair surveillance. Conclusions: With an increasing number of abdominal scans being performed in primary and tertiary settings, there is an associated increased volume of incidental findings that require work-up. This article outlines a practical investigation and management strategy for clinicians presented with VAAs, including in high-risk cohorts, emphasizing early imaging, inter-specialty coordination, and guideline-supported thresholds for intervention. Full article

Background/Objectives: Blunt abdominal trauma is a frequent challenge in emergency medicine, but its diagnosis and treatment become significantly more complex when rare anatomical anomalies are present. Atypical anatomy may mask symptoms or mimic other acute abdominal conditions, causing delays in treatment. The aim of this paper is to review the literature on six rare anatomical anomalies and their impact on the consequences of blunt abdominal trauma. Methods: A Narrative literature review was undertaken, covering PubMed, Scopus, Web of Science and Google Scholar databases, analysing publications from 1960 to 2025. Case reports and case series (91 patients in total) with confirmed organ damage following blunt trauma in the course of: duodenal diverticulum, Meckel’s diverticulum, splenic torsion, rupture or torsion of the accessory spleen, visceral inversion (situs inversus) and horseshoe kidney. Results: Demographic analysis revealed a predominance of perforations of the duodenal diverticulum in older women (mean age 62 years), while younger men predominated in all other groups. The clinical picture was often non-specific or misleading, especially in situs inversus, where the location of pain did not correlate with the typical topography of organs. Contrast-enhanced computed tomography (CECT) has proved to be a key diagnostic tool, surpassing ultrasound/FAST scans due to its ability to provide precise anatomical imaging. Surgical treatment was predominant (100% in Meckel’s diverticulum, 95% in duodenal diverticulum), while conservative treatment was effective in horseshoe kidney injuries (94.8%). Mortality was highest in situs inversus (29%) and duodenal diverticulum perforation (20%). The vast majority of these fatal cases occurred in the era of modern computed tomography, suggesting that the therapeutic challenges stem directly from the specific nature of these anomalies, rather than from past diagnostic limitations. Conclusions: Anatomical anomalies significantly modulate the clinical manifestations of blunt abdominal trauma, increasing the risk of diagnostic errors. Early contrast-enhanced computed tomography and awareness of these rare pathologies are crucial for appropriate management and improved prognosis. Full article

Background and objectives: Acute colicky abdominal pain, involving visceral spasms and inflammatory mechanisms, is a common complaint in everyday medical practice. Despite its widespread use, clinical evidence on the fixed-dose combination of pargeverine 10 mg plus lysine clonixinate 125 mg remains limited. The objective of this study was to describe real-world clinical outcomes, safety, and patient-reported experience associated with this combination in routine practice. Materials and methods: This multicenter, observational, non-comparative, real-world study included adult patients with acute colicky abdominal pain of gastrointestinal, urological, or gynecological origin. Pain intensity was assessed using a visual analog scale (VAS) at baseline and at 5 ± 3 days. Secondary outcomes included time to pain relief, satisfaction with treatment, and safety. Associations between pain reduction and patient-reported outcomes were explored. Results: A total of 202 patients were analyzed. Significant pain reduction was observed across all etiologies (p < 0.001), with median VAS reductions ranging from 6 to 9 points (approximately 70% to 90% from baseline). More than 95% of patients reported early improvement, and sustained relief was maintained in more than 96% throughout the study period, regardless of the pain’s origin. Adverse events were infrequent (3%), mild in intensity (primarily transient gastrointestinal symptoms), and did not lead to treatment discontinuation. Conclusions: In real-world clinical practice, the fixed-dose combination of pargeverine and lysine clonixinate was associated with early and sustained, clinically meaningful pain reduction across multiple forms of acute visceral colicky pain, with a favorable safety and tolerability profile, supporting its relevance as a short-term therapeutic option in mild to severe acute pain. Full article

Background: Visceral pain is the primary symptom of functional gastrointestinal disorders, yet its spinal molecular mechanisms remain poorly defined. Methods: Using a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced chronic inflammatory visceral pain model, the role of the spinal CXCL10/CXCR3/ERK signaling axis and the analgesic effect of docosahexaenoic acid (DHA) were investigated. Results: TNBS significantly upregulated CXCL10 and CXCR3 in spinal dorsal horn neurons and increased ERK phosphorylation. Intrathecal CXCL10-neutralizing antibody or CXCR3 antagonist NBI-74330 reduced visceral hypersensitivity and suppressed spinal ERK activation in TNBS mice. Exogenous CXCL10 induced CXCR3-dependent hyperalgesia and ERK phosphorylation in the spinal cord. Intrathecal DHA attenuated TNBS-induced visceral pain, downregulated spinal CXCL10/CXCR3 expression, and inhibited ERK signaling. In Neuro-2a cells, DHA also blocked LPS-induced activation of the same pathway. Conclusions: This study suggests that the analgesic effect of DHA may involve the inhibition of the spinal CXCL10/CXCR3/ERK signaling pathway. Full article

Transient receptor potential vanilloid 4 (TRPV4) is a polymodal cation channel that is widely expressed in sensory neurons, immune cells, and structural tissues, where it integrates mechanical, osmotic, and chemical stimuli to regulate both physiological responses and disease-associated signaling. Mast cells (MCs), key immune effector cells capable of rapid mediator release through degranulation, also express TRPV4. Increasing evidence supports TRPV4-MC signaling as an important neuroimmune interface, linking mechanical and inflammatory stimuli to tissue hypersensitivity and pain. In this review, we synthesize current evidence supporting a role for TRPV4 in MC-associated neuroimmune signaling across multiple disease contexts while distinguishing settings in which TRPV4 directly regulates MC activation from those in which MC responses arise through multicellular tissue interactions. Direct TRPV4-dependent MC activation has been described in conditions such as LL-37–driven rosacea and mechanically induced inflammation, whereas in disorders including asthma, visceral hypersensitivity, bladder pain syndromes, and osteoarthritis, TRPV4 activity in epithelial, neuronal, or stromal compartments more often influences MC function indirectly through ATP–purinergic signaling, cytokine release, and neuropeptide-mediated crosstalk. Across systems, TRPV4 emerges not as a single pathogenic switch but as part of a context-dependent signaling network whose functional consequences depend on cell type, tissue microenvironment, and disease stage. Altogether, these findings identify TRPV4 as a therapeutically actionable node within neuroimmune signaling pathways and support the development of tissue-specific and combination strategies targeting both TRPV4 activity and MC-mediated signaling in chronic inflammatory and pain disorders. Full article

Most patients with irritable bowel syndrome have diarrhea or constipation, two opposite bowel habits. Although defecation habits represent opposing phenotypes, patients across all subtypes exhibit visceral hypersensitivity. This review explores the common pathway that causes visceral hypersensitivity: the mast cell–PAR2–TRP axis. The mechanism involves tryptase released by mast cells. Furthermore, tryptase activates PAR2, which sensitizes downstream TRP ion channels that conduct pain signals. The review also examines the factors leading to the formation of different fecal characteristics. In terms of treatment, this review also summarizes therapeutic agents targeting different components of this axis. Future pharmaceutical research should focus more on the mast cell–PAR2–TRP axis. Full article

The clinical renaissance of psychedelic medicine has highlighted the therapeutic potential of rapid-acting neuroplastogens, or “psychoplastogens,” for psychiatric disorders. However, the widespread application of classical psychedelics—such as psilocybin and LSD—and the atypical dissociative ibogaine is severely limited by their hallucinogenic properties and, particularly in the case of ibogaine, life-threatening cardiotoxicity. Addressing these limitations, Tabernanthalog (TBG) has emerged as a frontrunner in the field. This non-hallucinogenic analog of ibogaine was rationally designed to eliminate interactions with the human ether-à-go-go-related gene (hERG, KCNH2) potassium channel, thereby mitigating cardiotoxic risks. While initially characterized for its anti-addictive and antidepressant-like properties, recent data from 2024–2025 have significantly expanded its therapeutic horizon. TBG demonstrates robust efficacy in preclinical models of neuropathic and visceral pain, as well as in the rescue of cognitive deficits associated with cancer-related cognitive impairment (CRCI). TBG has shown efficacy in reversing cognitive impairments induced directly by the presence of a tumor in preclinical models, rather than by chemotherapy-specific neurotoxicity. Crucially, emerging evidence suggests that TBG’s mechanism extends beyond simple 5-HT2A receptor agonism. New findings point to a multi-target profile involving the inhibition of nicotinic acetylcholine receptors (nAChRs), positive modulation of NMDA receptors, and functional crosstalk with mGlu2 receptors. Furthermore, TBG appears to induce structural neuroplasticity without the widespread induction of immediate early genes (IEGs) seen with classical hallucinogens, suggesting a decoupling of therapeutic rewiring from the subjective psychedelic experience. This review synthesizes current preclinical evidence to discuss TBG as a promising chemical scaffold for next-generation neurotherapeutics targeting the intersection of psychiatry and neurology. Full article