Neuropathic pain markedly impairs quality of life and imposes a substantial socioeconomic burden, while available treatments often provide only partial relief and are limited by safety concerns. The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG-IASP) first published pharmacologic recommendations in 2007, followed by a major update in 2015 and a new guideline in 2025. This narrative review specifically compares the 2015 and 2025 NeuPSIG-IASP guidelines, outlining key methodological changes and therapeutic shifts. The 2025 guideline is based on a larger, more rigorous meta-analysis, maintains α2δ-ligands (adds mirogabalin), serotonin-noradrenaline reuptake inhibitors, and tricyclic antidepressants as first-line drugs, downgrades tramadol into the opioid third-line group. It also introduces high-frequency motor-cortex repetitive transcranial magnetic stimulation as a weakly recommended third-line option and discusses implications for Korean clinical practice.

Background/Aims: Patients with postural tachycardia syndrome (POTS) commonly experience gastrointestinal (GI) symptoms. We aim to assess the feasibility and preliminary efficacy data for DA-9701, a prokinetic agent targeting 5-hy-droxytryptamine 1A, 5-hydroxytryptamine 4, and dopamine D 2 receptors, in patients with POTS. Methods: In a randomized, double-blind, placebo-controlled, single-center crossover trial, patients with POTS were given either 30 mg of DA-9701 or a placebo 3 times daily for eight weeks in a 1:1 ratio. After a 4-week washout, patients received the alternate treatment for another 8 weeks. The primary endpoint focused on assessing the change in GI symptoms (total Nepean Dyspepsia Index-Korean version [NDI-K] symptom score) from baseline over the 8 week-treatment period. Endpoints were assessed in all enrolled and randomized patients (intention-to-treat), and in those who completed the trial (per-protocol analysis). Results: Between January 2022 and August 2023, 24 patients were randomized (n = 12 per group), with 3 discontinuing after randomization. DA-9701 did not significantly improve primary endpoints for total NDI-K symptom scores in either the intention-to-treat (least-squares means, –13.9 vs. –9.5, P = 0.326) or per-protocol analyses (–17.2 vs –12.0, P = 0.242).Notably, a trend toward improvement in specific GI symptoms, such as upper abdominal pain, was observed in both intention-to-treat (–0.6 vs 0.7; P = 0.066) and per-protocol analyses (–0.9 vs 0.6; P = 0.045). No serious adverse events were observed. Conclusion DA-9701 did not improve GI symptoms in this crossover trial; however, its potential effect on specific GI symptoms merits further investigation.

Probiotics have gained increasing clinical attention as adjunctive treatment for lower gastrointestinal disorders. However, evidence supporting their therapeutic efficacy remains limited, particularly with regard to sex-related differences. This expert review provides evidence-based insights and practical recommendations for the use of probiotics in patients with irritable bowel syndrome (IBS), functional constipation (FC), and Clostridioides difficile infection (CDI), considering possible sex-related differences. Evidence from randomized controlled trials and meta-analyses indicates that probiotics can modestly improve global symptoms, abdominal pain, and bloating in IBS and enhance bowel movement frequency and stool consistency in FC. However, these effects are strain-specific and heterogeneous. Although clinical studies on probiotics in IBS have not confirmed significant sex-related differences, experimental animal studies using stress-induced IBS models have demonstrated sex-dependent responses to specific probiotic strains, supporting the biological plausibility of such differences. For CDI, the efficacy of probiotics in preventing primary or recurrent infections remains inconsistent across large trials, and current guidelines usually do not recommend their routine use. However, sex and age difference of immunology supports the clinical differences of CDI. Probiotics are generally considered safe for healthy individuals, although caution is advised in patients who are immunocompromised or critically ill. Clinicians should select probiotic products based on strain-specific clinical evidence, adequate viable doses, patient's characteristics, or patient’s sex. In conclusion, probiotics might play a role as adjunctive therapy for IBS and FC, with variability in responses influenced by microbial, host, and potential sex-related factors. Further research is needed to establish optimized personalized probiotic strategies.

Background/Aims: Spinal cord injury (SCI) frequently impairs defecation, severely affecting the quality of life. This study examines compensatory neural remodeling after SCI, focusing on basal colonic contractility, neural responses to electrical field stimulation, and alterations in excitatory cholinergic and inhibitory nitrergic pathways. Methods: Female Sprague–Dawley rats underwent either sham surgery or T10 spinal cord transection and were categorized into 3 groups: sham, 1-week post-SCI (acute), and 4-week post-SCI (chronic). Colonic contractility was assessed in an organ bath using electrical field stimulation in the presence of a nitric oxide synthase inhibitor. Neural protein expression was analyzed by immunofluorescence and Western blotting. Results: SCI produced region- and time-dependent impairments in colonic contractility, with distinct alterations in the proximal circular and longitudinal muscles across acute and chronic phases. Neural excitability shifted dynamically, showing enhanced excitatory activity in the proximal longitudinal muscle at 1-week and the distal circular muscle at 4-week post-SCI. Protein analysis revealed increased neuronal nitric oxide synthase in the proximal colon, decreasedsoluble guanylyl cyclase in the distal colon, upregulated muscarinic M3 receptor in the proximal colon, and reduced vaso-active intestinal peptide receptor 1 in both proximal and distal regions. Conclusion SCI induces spatiotemporal remodeling of excitatory and inhibitory neural pathways, contributing to colonic dysmotility and revealing potential targets for therapeutic intervention.

Background: This study aimed to investigate the effects of upper-extremity heat stress combined with resistance training and resistance training alone on body composition, skill and basal fitness, isokinetic muscle strength, and anabolic hormone levels in wheelchair rugby athletes with spinal cord injury. Methods: Fourteen male national wheelchair rugby athletes with cervical-level spinal cord injury were randomly assigned to the heat stress combined with resistance training (n=7) or resistance training group (n=7). Both groups completed a 10-week upper-extremity resistance training program. Additionally, heat stress was applied to the upper-extremity of the heat stress combined with resistance training group using steam-generating thermal sheets three times per week. Measurements conducted pre- and post-intervention included body composition, skill and basal fitness (one-hand throw, chest throw, 28 m shuttle sprint, and 20 m sprint), isokinetic strength (using the Cybex system at 60°/sec and 180°/sec), and anabolic hormones (growth hormone and insulin-like growth factor). Non-parametric tests (Wilcoxon signed-rank and Mann-Whitney U test) were used for statistical analysis (α=0.05). Results: The heat stress combined with resistance training group showed significant increases in skeletal muscle mass and upper-extremity isokinetic elbow joint strength, particularly in flexion (%BW) and extension (%BW) at 60°/sec. Growth hormone levels increased significantly only in this group, while insulin-like growth factor levels showed marginal improvement. Both groups improved in 28 m shuttle sprint and one-hand throw; however, the heat stress combined group showed a greater effect size in the 20 m sprint. No significant changes were observed in body mass index or body fat percentage. Conclusions The combination of heat stress and resistance training may provide additional benefits in enhancing upper-extremity muscle strength and stimulating anabolic hormone responses in wheelchair rugby athletes with spinal cord injury. These findings suggest a promising and practical strategy for optimizing training adaptations in this athletic population.

Probiotics have gained increasing clinical attention as adjunctive treatment for lower gastrointestinal disorders. However, evidence supporting their therapeutic efficacy remains limited, particularly with regard to sex-related differences. This expert review provides evidence-based insights and practical recommendations for the use of probiotics in patients with irritable bowel syndrome (IBS), functional constipation (FC), and Clostridioides difficile infection (CDI), considering possible sex-related differences. Evidence from randomized controlled trials and meta-analyses indicates that probiotics can modestly improve global symptoms, abdominal pain, and bloating in IBS and enhance bowel movement frequency and stool consistency in FC. However, these effects are strain-specific and heterogeneous. Although clinical studies on probiotics in IBS have not confirmed significant sex-related differences, experimental animal studies using stress-induced IBS models have demonstrated sex-dependent responses to specific probiotic strains, supporting the biological plausibility of such differences. For CDI, the efficacy of probiotics in preventing primary or recurrent infections remains inconsistent across large trials, and current guidelines usually do not recommend their routine use. However, sex- and age-related immunologic differences support the clinical differences of CDI. Probiotics are generally considered safe for healthy individuals, although caution is advised in patients who are immunocompromised or critically ill. Clinicians should select probiotic products based on strain-specific clinical evidence, adequate viable doses, patient characteristics and sex. In conclusion, probiotics might play a role as adjunctive therapy for IBS and FC, with variability in responses influenced by microbial, host, and potential sex-related factors. Further research is needed to establish optimized personalized probiotic strategies.

Purpose: While MRI-based tumor regression grade (mrTRG) has shown promise in evaluating pathologic response to concurrent chemoradiotherapy (CCRT) in rectal cancer, its ability to predict pathologic complete response remains limited.This study aimed to enhance mrTRG’s diagnostic performance in predicting ypT0–1N0 status, a key factor in considering non-radical management after CCRT for locally advanced rectal cancer (LARC). Methods: This retrospective study included 430 patients with LARC who underwent radical resection following CCRT at a single referral hospital between April 2018 and September 2024. Multivariable logistic regression was used to identify predictive factors associated with achieving ypT0–1N0 status. The diagnostic performances of mrTRG1–2 alone and in combination with other factors were assessed by comparing sensitivity, specificity, positive-predictive value (PPV), negative-predictive value, and area under the curve (AUC). Results: Ninety-three patients (21.6%) achieved ypT0–1N0. In the multivariable analysis, fungating type, cT1–2, and mrTRG1–2 were independent predictors for ypT0–1N0. Integrating mrTRG with gross tumor type yielded the highest AUC of 0.689 among the combined models. For predicting ypT0–1N0, the combination of mrTRG and gross tumor type improved PPV (79.2% vs. 41.5% for mrTRG alone) while also demonstrating enhanced sensitivity compared with ycT0–1N0, the conventional MRI-based predictor (40.9% vs. 22.6%). Conclusion This study demonstrated that combining mrTRG and gross tumor type improved the PPV of mrTRG in predicting ypT0–1N0 after CCRT in LARC. Further studies are warranted to validate the role of gross tumor type in refining predictive systems for selecting candidates for non-radical treatment.

Recurrent scalp compromise following deep brain stimulation (DBS) implantation remains a challenging reconstructive problem, particularly in patients with chronic infection and repeated revision procedures. We present an acellular dermal matrix (ADM)-assisted salvage strategy using rotational scalp flap coverage with adjunctive calvarial recession for preservation of exposed DBS hardware. After debridement and subperiosteal flap elevation, ADM was applied over the exposed hardware as a biologic reinforcement layer prior to tension-free closure. Adjunctive calvarial recession was performed to reduce hardware prominence. Postoperative computed tomography demonstrated decreased hardware projection, and stable wound healing without recurrent dehiscence or infection was maintained during follow-up. This combined approach may represent an effective salvage option for recurrent DBS scalp compromise while preserving functional neuromodulation hardware.

Conventional aryl hydrocarbon receptor (AhR) antagonists, which play a critical role in modulating tumor immune evasion, have shown limited clinical translation due to poor solubility, restricted systemic exposure, and dose-limiting toxicities. To overcome these limitations, we developed SB5794, a phosphate prodrug of the potent AhR antagonist SB2617, designed to improve aqueous solubility and pharmacokinetic properties. SB5794 exhibited markedly enhanced solubility and achieved more than six-fold higher systemic exposure in mice compared with SB2617, while fully retaining its in vitro AhR antagonistic activity. In syngeneic tumor models, SB5794 significantly inhibited tumor growth, and its combination with anti–PD-1 therapy further enhanced antitumor efficacy. However, repeated-dose studies revealed dose-dependent histopathological changes in the gastrointestinal tract, liver, and immune organs. Collectively, these findings demonstrate that SB5794 possesses improved drug-like properties and strong immunomodulatory activity, supporting its potential as a next-generation AhR-targeted immunotherapeutic candidate.

This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.