Chronic nonspecific low back pain (CNSLBP) is a common condition often associated with impaired diaphragmatic and trunk function. The therapeutic effect of diaphragmatic myofascial release (DMR) in this population requires clarification. The aim of this study was to investigate the short-term effects of DMR on pain, mobility, balance, and disability in CNSLBP. In a randomized sham-controlled trial, twenty-four adults with CNSLBP were randomly assigned to receive three sessions of either DMR or a sham intervention. Both groups also received standardized transcutaneous electrical nerve stimulation (TENS). The primary outcome was pain intensity measured on a Visual Analog Scale (VAS). Secondary outcomes included lumbopelvic mobility (fingertip-to-floor test), static and dynamic balance (single-leg stance and functional reach tests), disability (Roland-Morris Disability Questionnaire, RMDQ), and chest expansion, were measured at baseline, after the third intervention session, and at one-week follow-up. A significant group × time interaction was detected for VAS (p < 0.001, η²ₚ = 0.33); the intervention group showed a significantly larger pain reduction than the sham group. Fingertip-to-floor also showed a significant group × time interaction (p = 0.04, η²ₚ = 0.13). Post-hoc tests showed a non-significant trend towards improvement in the intervention group from baseline to post-intervention (MD = 2.54 cm, p = 0.07) and from baseline to follow-up (MD = 1.93 cm, p = 0.08), whereas no such trend was observed in the control group (p > 0.05). Single-leg stance tests improved over time in both groups (p < 0.01) but there was no significant group × time interaction. No significant group or interaction effects were observed for functional reach or chest expansion. The RMDQ score decreased significantly in both groups, and the between-group comparison for disability change scores was statistically significant (p = 0.036), favoring the intervention group. DMR combined with TENS resulted in greater short‑term pain reduction and disability improvement, both exceeding minimal clinically important differences, compared with sham, and a non‑significant trend toward improved lumbar mobility. Static balance improved over time in both groups, with no between‑group differences. These results support DMR as a promising adjunct for managing pain, disability, and potentially balance in CNSLBP, but larger trials are needed to confirm its specific effects.Trial registration: IRCT20221216056836N1 (IRCT), registered on 28 February 2023.

Trigeminal neuralgia (TN) is a debilitating orofacial pain disorder for which current treatments often provide incomplete or transient relief and do not address mechanisms that sustain chronic pain. Here, we identify neuropeptide Y (NPY) acting via the Y2 receptor (Y2R) as a previously unrecognized neuroimmune driver of TN and as a tractable therapeutic target. We prospectively enrolled 92 patients (TN and hemifacial spasm cohorts) and measured NPY concentrations in quality-controlled plasma and cerebrospinal fluid (CSF) samples (n = 40 per group for each biofluid) by ELISA. CSF, but not plasma, NPY was significantly elevated in TN patients and correlated with pain intensity, indicating that CSF NPY reflects compartmentalized trigeminal ganglion (TG) disease activity. Using a mouse model of partial infraorbital nerve transection (pT-ION), we show that injured TG neurons upregulated and released NPY. NPY acted on neighboring nociceptors via the Y2R, recruiting and activating TG macrophages, which released TNF-α and increased neuronal excitability, thereby establishing a self-amplifying neuron-macrophage feedback loop that sustained local neuroinflammation and mechanical allodynia. Pharmacological Y2R blockade (BIIE0246), genetic Npy2r deletion, or macrophage depletion each robustly reversed established allodynia. Together, these findings reveal NPY-Y2R as a mechanistic driver of TN, establish CSF NPY as a clinically relevant candidate biomarker for TN-associated pain, and highlight TG-directed Y2R as a promising strategy for mechanism-based therapy development.

P2X receptors (P2XRs) are ATP-gated cation channels that play a pivotal role in chronic visceral pain (CVP). This review highlights the central contribution of the ATP-P2X3/4/7 axis in peripheral and central sensitization underlying CVP. Recent discoveries have identified the non-coding RNA miR-1306-3p as an endogenous nanomolar agonist of P2X3 receptors, coupling chronic stress to visceral pain via an epigenetic pathway. Moreover, persistent DNA methylation changes at the P2RX7 locus in spinal astrocytes create a "pain memory" that limits the durability of conventional antagonists. The first-generation P2X3/P2X7 antagonists (e.g., AF-219, AZD-9056, NC-2600) failed in clinical trials, primarily due to species-specific receptor pharmacology, the lack of ATP-based biomarkers for patient stratification, and irreversible central sensitization driven by epigenetic marks. To overcome these hurdles, we propose a precision-medicine framework that includes: (1) CRISPR-dCas9-based epigenome editing as a potential one-time "pain-memory eraser"; (2) patient stratification using sweat-ATP levels; and (3) human iPSC-derived neuron screening to improve translational predictability. This integrated approach holds promise not only for CVP related to irritable bowel syndrome (IBS), but also for other pain conditions.

We report a case of a 64-year-old woman who had a subcutaneous schwannoma accompanied by hemorrhagic cystic degeneration in the left lower extremity. The patient presented with a progressively enlarging subcutaneous mass over an 8-year course, accompanied by activity-induced dull pain. Physical examination revealed a firm, well-defined nodule measuring 5.0 × 3.5 × 0.5 cm, with a negative Tinel's sign. Ultrasonography initially led to misdiagnosis of the lesion as a hemangioma; histopathological examination following complete surgical excision confirmed schwannoma. Microscopic analysis demonstrated characteristic Antoni A areas (featuring palisading spindle cells and Verocay bodies) and Antoni B (showing myxoid degeneration, cystic changes, and hyalinized vasculature). Subcutaneous schwannomas are prone to misdiagnosis because of the absence of typical imaging features. This imaging limitation necessitates a multidimensional analysis that integrates imaging with clinical manifestationsand histopathological features for accurate identification and differential diagnosis. Complete surgical excision achieved local disease control, and no recurrence was observed during the 4-year follow-up.This case highlights the importance of considering schwannoma in the differential diagnosis of chronic subcutaneous lower extremity masses. Establishing a "clinical-imaging-pathology" tripartite diagnostic framework is critical for early and precise management.Although photodynamic therapy or photodiagnosis was not performed in the present case, accurate recognition of rare superficial tumors with atypical manifestations may support appropriate lesion characterization before selecting diagnostic or therapeutic strategies, including photo-based approaches when clinically applicable.