Search Results (106)

Background: Neuropathic pain (NP) is a chronic pain condition caused by a lesion or disease of the somatosensory nervous system. Its development and persistence are closely associated with peripheral nociceptive input, central sensitization, neuroimmune dysregulation, and remodeling of the local metabolic microenvironment. Our previous studies demonstrated that combined treatment with ligustrazine and sinomenine ameliorates early sciatic nerve pathological damage and systemic metabolic disturbances in rats with chronic constriction injury (CCI). However, whether this combination modulates central sensitization in NP remains unclear. Objective: This study aimed to evaluate the effects of combined ligustrazine and sinomenine treatment on pain-related behaviors and motor function during the maintenance phase of CCI-induced neuropathic pain and to investigate the potential mechanisms underlying its attenuation of central sensitization, with particular emphasis on metabolic remodeling, neurotransmitter homeostasis, and associated regulatory molecules in the spinal dorsal horn. Methods: A rat model of CCI was established, and animals were treated with ligustrazine combined with sinomenine (12.5 + 12.5, 25 + 25, or 50 + 50 mg/kg) for 7 consecutive days. Mechanical withdrawal threshold, cold hypersensitivity, and gait behavior were assessed. A multiplex assay was used to profile 12 plasma inflammatory cytokines and pain-related mediators. Integrated transcriptomic and metabolomic analyses of the spinal dorsal horn were subsequently performed to identify key altered pathways. Oxylipin profiling, targeted neurotransmitter analysis, and quantification of metabolites associated with the arginine–polyamine pathway were further conducted to characterize alterations in the local metabolic microenvironment associated with central sensitization. Finally, quantitative real-time PCR (qRT-PCR) and Western blotting were used to evaluate molecules related to polyamine metabolism, redox homeostasis, and central sensitization. Results: Combined ligustrazine and sinomenine treatment improved pain-related behaviors and gait dysfunction in CCI rats and partially normalized systemic inflammatory dysregulation. The ipsilateral-to-contralateral maximum contact-area ratio decreased from 102.8 ± 9.0% in the Sham group to 53.1 ± 9.7% in the Model group and recovered to 85.5 ± 4.4% in the high-dose group. Metabolomic and transcriptomic analyses identified 54 differential metabolites and 130 differentially expressed genes, respectively, following treatment. Integrated multi-omics analysis highlighted arginine-related metabolic pathways, together with alterations in neurotransmitter, polyamine, oxylipin, and redox homeostasis. Full article

Descending pain modulation is a major determinant of pain processing across physiological and pathological conditions. Although descending pain modulation has long been recognized as bidirectional, capable of both inhibiting and facilitating nociceptive transmission, recent advances now allow it to be examined with far greater anatomical, cellular, neurochemical, and functional precision. Circuit tracing, optogenetic and chemogenetic manipulation, molecular profiling, connectomics, and human neuroimaging have expanded classical brainstem models, revealing a modulatory network in which inhibitory and facilitatory influences are dynamically recruited according to physiological and pathological state. In this narrative review, we revisit descending pain modulation across acute, inflammatory, neuropathic, and nociplastic pain states. We discuss canonical pathways, including the periaqueductal gray–rostral ventromedial medulla axis and locus coeruleus–spinal noradrenergic projections, together with the established dorsal reticular nucleus system and more recently identified descending circuits. We examine how circuit organization, neurochemical diversity, and local and long-range network interactions shape modulatory output across pain conditions. Attention is given to state-dependent plasticity and to the progressive reorganization of descending systems during pain chronification. In this context, reduced inhibitory flexibility and enhanced facilitatory bias emerge as recurrent, but not uniform, features of chronic pain. We also consider how human experimental paradigms, pharmacological approaches, and neuroimaging findings can be interpreted in light of these mechanistic advances, while acknowledging the limits of translating circuit-specific animal findings into integrated human measures. By framing descending pain modulation as a distributed and dynamically reconfigurable network rather than as a unitary analgesic system, this review highlights its relevance to pain phenotyping, treatment stratification, and mechanism-informed therapeutic strategies. Full article

Orofacial pain is a multifactorial condition that severely impacts basic functions and overall quality of life in patients, underscoring the need for non-opioid therapeutic strategies. Targeting the Transient Receptor Potential Vanilloid 1 (TRPV1) pathway has emerged as a biologically plausible approach, given its central role in nociceptive transduction and peripheral sensitization. Capsaicin, a selective TRPV1 agonist, induces receptor desensitization and has shown potential in chronic pain modulation; however, its efficacy in orofacial conditions remains unclear. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of capsaicin in managing orofacial pain, compared to placebo or other pharmacological interventions. Following PRISMA guidelines, a comprehensive search of five databases (PubMed, Scopus, Web of Science, CDSR, and LILACS) was conducted without language or date restrictions. Studies involving human participants with orofacial pain treated with capsaicin were included. The protocol was registered in PROSPERO (CRD420251004538). Risk of bias was assessed using the RoB2, RoB2 crossover trial and ROBINS-I checklist, and meta-analyses were performed using random-effects models. Nine studies enrolling a total of 164 participants met the eligibility criteria and encompassed temporomandibular disorders, burning mouth syndrome, oral mucositis, trigeminal neuralgia, and neuropathic facial pain. Although placebo-controlled comparisons showed a trend toward pain reduction that did not reach statistical significance (MD = –1.87; [95% CI: –3.94, 0.19]; p = 0.08; I² = 86%), and no significant difference was found between capsaicin concentrations (MD = 0.46; [95% CI: –2.67, 3.60]; p = 0.77, I² = 66%), pre–post analyses of uncontrolled (single-arm) studies demonstrated a significant and clinically meaningful reduction in pain following capsaicin treatment (MD = –6.39; [95% CI: –7.40, –5.38; p < 0.001, I² = 0%). Capsaicin also showed an acceptable safety profile: although adverse events were significantly more frequent than with control (OR = 19.84; [95% CI: 4.32–91.21]; p < 0.001, I² = 0%), these were mild, localized, and self-limited. Capsaicin may provide clinically meaningful pain relief in selected orofacial conditions, particularly burning mouth syndrome, where uncontrolled evidence was most consistent (I² = 0%); evidence for temporomandibular disorders was more heterogeneous and did not reach significance in pooled placebo-controlled analyses. Full article

Perineural invasion (PNI) is a distinct route of cancer spread associated with neuropathic pain, local recurrence, and poor survival across many solid tumours. Increasing evidence shows that PNI is not only a structural pattern of invasion but also a dynamic biological process involving neurodegeneration, nociceptor sensitisation, and marked local immunosuppression. This narrative review synthesises experimental, translational, and clinical data on the molecular, neurological, and immunological mechanisms of PNI in solid malignancies. PNI arises through complex crosstalk between tumour cells, Schwann cells, macrophages, fibroblasts, and neurotrophic pathways, leading to peripheral nerve remodelling, axonal degeneration, and abnormal regeneration. These changes promote neuropathic pain through ion-channel dysregulation, neurotrophin-driven sensitisation, and pathological neuroplasticity. At the same time, PNI creates an immunosuppressive microenvironment enriched in Tregs, M2 macrophages, and myeloid-derived suppressor cells, shaped by cholinergic, adrenergic, and neuropeptidergic signalling, which may contribute to immune exclusion and resistance to immunotherapy. We propose that PNI should be understood as a neuro-immuno-metabolic process and that recognising the PNI–pain–immunosuppression triad may support the development of targeted neuroprotective, analgesic, and immunomodulatory therapies. Full article

Spinal cord injury (SCI) is a devastating neurological disorder. The development of effective therapies to ameliorate the consequences of SCI represents a major challenge and a central priority of international biomedical research. The stromal vascular fraction (SVF) derived from adipose tissue possesses considerable functional potential. SVF is a heterogeneous mixture of cells that act synergistically. However, after local transplantation, SVF is rapidly cleared via the bloodstream, and its poor survival severely compromises therapeutic efficacy. To overcome this limitation, we employed a self-assembling peptide nanohydrogel HGF-RADA16-IKVAV (where HGF denotes the tripeptide histidine–glycine–phenylalanine) as a scaffold to enhance SVF retention and efficacy in a rat model of SCI. Implantation of SVF and HGF into the injured spinal cord demonstrated that this combined therapy significantly modulated the inflammatory response, increased neuronal survival, and promoted a denser network of axon tracts. Consequently, the SVF-encapsulated HGF hydrogel resulted in superior restoration of limb movement and reduced neuropathic pain. Proteomic analysis confirmed that the combined treatment shifted the injury-induced molecular landscape, particularly in immune and inflammatory pathways. Collectively, these findings demonstrate that this combinatorial strategy represents an effective therapeutic paradigm for SCI. Full article

Introduction: Pain is one of the most common reasons why patients seek medical care, and chronic pain is now recognized as a major health problem worldwide. Better understanding of pain mechanisms has shown the importance of distinguishing nociceptive, neuropathic, and nociplastic pain in order to choose the most effective treatment. In recent years, topical analgesics have gained increasing attention because they can provide pain relief directly at the site of application while reducing systemic exposure and the risk of adverse effects. This is especially important in older adults, patients with multiple diseases, and those exposed to polypharmacy. Methods: This narrative review presents the current knowledge on the pharmacology, efficacy, and safety of topical drugs used in pain treatment. Particular attention is given to topical non-steroidal anti-inflammatory drugs (NSAIDs), lidocaine, capsaicin, menthol, and camphor. The review also discusses newer and less established therapies used mainly in neuropathic pain, including topical ketamine, amitriptyline, phenytoin, gabapentin, and clonidine. A structured, non-systematic literature search was conducted using the PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar databases to identify studies evaluating the efficacy and safety of topical analgesic therapies. Results: Current evidence supports topical NSAIDs as first-line therapy for localized musculoskeletal pain and osteoarthritis, while lidocaine and high-concentration capsaicin patches are effective options in focal neuropathic pain. Although several newer topical therapies show promising results, more high-quality clinical studies are still needed. Overall, topical analgesia is an important part of multimodal pain management because it combines analgesic efficacy with a better safety profile compared with many systemic therapies. Conclusions: Taking the aspects discussed in this paper into account, it seems justified to search for new drug combinations that would contribute to effective pain therapy with topical agents. It is recognized that a multimodal approach to pain management, which utilizes drugs with different mechanisms of action, can increase efficacy and reduce the systemic adverse events of the drugs used. The effective and safe treatment of patients with pain, especially neuropathic pain, despite emerging new clinical trials, remains a challenge for clinicians. Full article

Background/Objectives: Chronic pain is a significant clinical challenge, in part due to the absence of reliable objective biomarkers for its evaluation and treatment. Growing evidence indicates that immune cells, including natural killer (NK) cells, are involved in the regulation of pain processes. NK cells are innate cytotoxic lymphocytes whose functional status may mirror underlying pathological pain states. In this study, we investigated μ-opioid receptor (MOR) expression and functional alterations of NK cells in a murine model of neuropathic pain induced by chronic constriction injury (CCI). Methods: Mice were divided into three groups: Sham (sciatic nerve exposure without ligation), CCI 14-day, and CCI 21-day groups. At the respective time points, animals were sacrificed and spleens were collected for analysis. Splenocytes were isolated by mechanical dissociation followed by centrifugation and erythrocyte lysis. Lymphocytes were analyzed by flow cytometry to evaluate MOR expression in NK cells and their degranulation activity (CD107a assay). Cells were incubated with fluorochrome-conjugated antibodies against NK cell markers (NK1.1, CD3, Ly49A, Ly49C/I) in combination with anti-MOR and anti-Interferon γ antibody (IFN-γ). Immunofluorescence and confocal microscopy analyses were performed to assess MOR localization and granzyme localization, supporting CD107a-mediated degranulation. Results: Flow cytometry analysis revealed a significant reduction in surface MOR expression on total NK cells from CCI mice compared with sham controls at 14 and 21 days post-injury, a finding corroborated by immunofluorescence evidence of MOR cellular internalization. Functionally, CCI induced a marked decrease in CD107a expression and impaired IFN-γ production both under basal conditions and following PMA/ionomycin stimulation, indicating a hyporesponsive state of NK cells. Consistently, confocal microscopy revealed extracellular release of Granzyme A following CCI, suggesting dysregulated degranulation. Conclusions: Neuropathic pain is associated with a remodeling of NK cell phenotype and effector functions, characterized by impaired cytotoxic activity and cytokine production, along with modulation of inhibitory receptor expression. Notably, MOR-reduced surface expression in NK cells emerges as a potential biomarker of neuropathic pain. Further studies are needed to elucidate the molecular mechanisms regulating MOR expression and its relationship with NK cell hyporesponsiveness and degranulation in chronic pain conditions. Full article

Background/Objectives: Trigeminal neuralgia (TN) is a debilitating neurological condition characterized by recurrent, severe pain linked to peripheral and central sensitization within trigeminal pathways. Current pharmacologic treatments are limited by inadequate efficacy or dose-limiting side effects, and botulinum neurotoxin type A (BoNT/A) has emerged as a viable option. However, its potential use in the management of TN is hampered by methodological limitations in existing studies and a lack of pivotal clinical trials. This study investigated the efficacy, optimal treatment site, preventive utility, and duration of effect of incobotulinumtoxinA (Inco/A), a BoNT/A, in a model of TN. Methods: An infraorbital nerve chronic constriction injury model was used to induce mechanical allodynia in male Sprague–Dawley rats, reproducing the trigeminal sensitization seen in TN. The effects of subcutaneous Inco/A (1, 2, and 4 U) were measured using the mechanical sensitivity (von Frey) test to evaluate the dose response, effect of injection location, potential preventive nature of treatment, and duration of benefit. Results: Inco/A produced a robust, dose-dependent reduction in mechanical allodynia, predominantly via a local mechanism of action. Both preventive and therapeutic administration of Inco/A was efficacious, with significant reduction in allodynia even when administered up to 28 days before nerve injury. The anti-allodynic effect persisted up to 56 days post-injection. Conclusions: Inco/A is highly effective in alleviating mechanical allodynia in a validated rat model of TN. The findings highlight Inco/A as a promising candidate for clinical translation in TN and related neuropathic pain syndromes and support systematic investigation in well-controlled human trials. Full article

Background: Peripheral neuropathy is a common and clinically heterogeneous neurological condition caused by metabolic, inflammatory, toxic, or traumatic factors and is associated with sensory deficits, neuropathic pain, motor impairment, and reduced functional capacity. Management remains challenging and often requires multimodal therapeutic approaches, as pharmacological monotherapy frequently provides incomplete symptom control. Objective: This narrative review explores the conceptual rationale for combining galantamine with iontophoresis and Black Sea brine-based therapy as a potential multimodal strategy for peripheral neuropathy management. Main Findings: Galantamine, a reversible acetylcholinesterase inhibitor and positive allosteric modulator of nicotinic acetylcholine receptors, has demonstrated neuroprotective, neuromodulatory, and anti-inflammatory properties in experimental settings. Iontophoresis may provide a non-invasive method for targeted local drug delivery while reducing systemic exposure. Black Sea brine, widely used in Bulgarian balneological and rehabilitation practice, has been associated with improved circulation, pain reduction, and neuromuscular support. The reviewed evidence suggests biologically plausible complementary mechanisms; however, no direct clinical studies evaluating the combined intervention were identified. Limitations: Current evidence is indirect and derived from separate investigations of galantamine, iontophoresis, and brine-based therapy, as well as heterogeneous historical and regional sources. Therefore, the proposed combination should be considered hypothesis-generating rather than evidence-established. Conclusions: The combination of galantamine, iontophoresis, and Black Sea brine represents a potentially interesting multimodal concept for peripheral neuropathy rehabilitation. Well-designed preclinical and clinical studies are required to determine safety, feasibility, optimal treatment parameters, and therapeutic efficacy. Full article

Pharmacotherapy of neuropathic pain (NP) remains challenging due to its heterogeneous etiology, lack of objective diagnostic tools, and the limited efficacy of currently available treatments, including antidepressants, anticonvulsants, and local anesthetics. Therefore, the search for novel therapies with improved analgesic efficacy and reduced adverse effects is of growing importance. In this context, natural alkaloids have emerged as promising candidates, demonstrating analgesic potential in both diabetes-induced neuropathy and various experimental models of NP. This review outlines NP pathophysiology, emphasizing maladaptive changes within the somatosensory nervous system, including peripheral and central sensitization, as well as glial cell activation. Furthermore, it discusses the mechanisms through which alkaloids may modulate NP-related pathways, with particular focus on their interactions with ion channels, signaling pathways, inflammatory responses, and oxidative stress. A literature search was conducted using the Scopus, Google Scholar and PubMed databases for papers published between 2015 and 2026, using the keywords “alkaloids” and “neuropathic pain”, and focused on recent findings regarding the antinociceptive effects of berbamine, tetrandrine, fangchinoline, and sinomenine, and their derivatives. The analysis indicates that, despite promising preclinical evidence, further rigorous preclinical and clinical studies are necessary to fully assess their therapeutic potential in the treatment of NP. Full article

Background/Objectives: Acrodermatitis chronica atrophicans (ACA), a late cutaneous manifestation of Lyme borreliosis, presents with a broad clinical spectrum. Most commonly, a characteristic bluish-red patchy rash, but it can also appear as unilateral limb swelling. This study aimed to characterize the clinical manifestations, diagnostic workup, and outcomes of patients with ACA in a tertiary setting in Denmark. Methods: Retrospective cohort study including all patients diagnosed with ACA at Copenhagen University Hospital-Rigshospitalet between 2017 and 2025. Results: Forty patients were included (median age 57 years; 63% female), with a median BMI of 24.5 [range 15.6–36.3]. Symptom duration was long (median 1 year). All patients presented with a skin rash. The most common location was the lower extremity, 26/40 (65%). Local edema and neuropathic pain were common (20/40) 50% and (23/40) 55%, respectively. A total of 13/40 patients underwent lymphoscintigraphy, which was deemed pathological in 7/13 (54%). The patients presenting with edema underwent significantly more imaging procedures, median 3 (range 1–5) vs. 0 (range 0–2), p < 0.005; they were younger, median age 49 years (range 17–76) vs. median 65 (range 30–81), p = 0.03; but did not differ in BMI, median 26.6 (range 19.0–36.2) versus median 23.8 (range 15.6–36.3), p = 0.48. All patients were Borrelia burgdorferi (Bb) IgG seropositive. Borrelia-specific PCR was positive in 6/13 (46%). Histopathology supported the diagnosis in 19/20 (95%). Clinical evaluation of the treatment response at 3 months was good in 33/40 (83%). Conclusions: Edema/swelling due to lymphatic obstruction is a common presentation of ACA in the tertiary setting, resulting in extensive diagnostic workup. The condition is associated with younger age but not BMI, sex, or immunodeficiency. Raised awareness and earlier testing for Bb IgG in serum seem warranted. Full article

Background/Objectives: The role of muscle trigger points (TrPs) in neuropathic pain (NP) components in whiplash-associated disorders (WAD) has not been investigated. Our aim was to systematically investigate if referred pain elicited by trigger points (TrPs) in neck musculature reproduces neuropathic pain (NP) characteristics in chronic whiplash-associated disorders (WAD) and to determine the association of TrPs with pain intensity, mechanosensitivity, and disability. Methods: An exploratory cross-sectional study was conducted (n = 64; chronic WAD: n = 32; age- and sex-matched healthy controls: n = 32). TrPs in upper trapezius, suboccipital, splenius capitis, levator scapulae, scalene, and sternocleidomastoid muscles were evaluated. Pain intensity, NP components, pain catastrophizing, and disability were assessed with an 11-point numerical pain rating scale (0–10), NP questionnaires (Douleur Neuropathique 4 [DN4], self-administered Leeds Assessment of Neuropathic Symptoms and Signs [S-LANSS], and Neuropathic Pain Symptom Inventory [NSPI]), the Pain Catastrophizing Scale, and the Neck Disability Index, respectively. Mechanosensitivity (pressure pain thresholds) was assessed bilaterally over C2–C3 and C5–6 zygapophyseal joints, second metacarpal, and tibialis anterior muscle. The Mann–Whitney U test and advanced chi-square (χ²) test, including rank-based ANCOVA adjusted for age and sex, were used for comparisons between groups. Additionally, multivariate analyses were also performed (rank-based MANCOVA adjusted for age, sex, and pain intensity). Spearman’s rho (r_s) and LOESS regression analysis, corroborated with linear regression and/or polynomial regression coefficient analysis, were used to explore associations between clinical variables in WAD. Results: Significant differences in distribution of TrPs, with a significant effect of sex, were found between groups (p < 0.05). In WAD, a greater number of active TrPs, mostly prevalent in levator scapulae and suboccipital muscles, was associated with higher pain intensity, number and intensity of NP components, and disability (0.372 < r_s < 0.570, p < 0.05), or local mechanical hyperalgesia (r_s = −0.362, p < 0.05). Conclusions: Referred pain elicited by active TrPs in the neck muscles reproduced NP symptoms in chronic WAD. This study contributes to a new understanding of pain mechanisms in WAD, highlighting the role of active TrPs in generating or maintaining NP symptoms and sensitization processes. Full article

Background and Objectives: Chronic headache after craniotomy is common and may include neuropathic subtypes (scar neuroma pain, occipital neuralgia). However, no large series has quantified these phenotypes. We conducted a single-center retrospective review (n = 5624 adult craniotomy patients) to estimate the prevalence of post-craniotomy neuropathic pain and to describe its characteristics. Materials and Methods: Institutional records were screened to identify craniotomy patients referred to a multidisciplinary pain clinic (n = 272). Eligible cases were reviewed in tiers: (1) exclusion of primary headache and noncranial pain; (2) identification of “probable neuropathic cranial pain” based on documented neuropathic features (lancinating/scalp pain, trigger tenderness, dermatomal distribution); and (3) subgroup categorization into occipital neuralgia-like, supraorbital/supratrochlear neuralgia-like, and scar-site neuropathic pain phenotypes. The supraorbital/supratrochlear subgroup was defined by frontal or frontotemporal postoperative pain in the supraorbital region, local tenderness or Tinel-like hypersensitivity over the supraorbital/supratrochlear course, and/or response to supraorbital–supratrochlear nerve block. Data extracted included demographics, timing (surgery to pain referral), pain characteristics, and treatments (blocks, radiofrequency, medications). Results: Of 5624 craniotomy patients, 272 (4.8%) had pain clinic encounters. The initial review identified 124 cases with chronic post-craniotomy headache requiring follow-up; after detailed chart classification, probable neuropathic cranial pain was present in 111 cases (2% of the cohort). Among the 111 probable neuropathic cranial pain cases, the dominant regional phenotype was occipital neuralgia-like pain. In addition, eight patients (7.2%) demonstrated a supraorbital/supratrochlear neuralgia-like phenotype, predominantly after frontal or frontotemporal craniotomies. Scar-site neuropathic pain frequently coexisted with both regional phenotypes, supporting a partially overlapping spectrum rather than mutually exclusive categories. The median time from surgery to pain referral was several months (≈12–18 months). Management commonly included occipital nerve blocks (±steroid); some patients received pulsed radiofrequency ablation of the occipital nerves, and most were trialed on neuropathic analgesics (gabapentinoids, SNRIs, etc., according to neuropathic pain guidelines). Conclusions: A clinically meaningful subset of post-craniotomy patients develops chronic neuropathic cranial pain, most commonly with occipital, supraorbital/supratrochlear, or scar-related features. Because most postoperative headaches are managed through neurosurgical follow-up and improve without pain clinic referral, the present cohort likely underestimates the true burden of neuropathic post-craniotomy pain while enriching for its most refractory neuralgic presentations. This is nevertheless the subgroup that must be recognized, discussed with patients, studied prospectively, and targeted in future prevention strategies. Full article

Background/Objectives: Stereotactic body radiation therapy (SBRT) provides improved pain response and local control for spinal metastases. However, management of local failure after initial SBRT is challenging. We report institutional outcomes, dosimetry, and toxicity for reSBRT following SBRT. Methods: We retrospectively reviewed 61 lesions (55 patients) treated with reSBRT after prior SBRT. Both SBRT courses delivered a median dose of 27 Gy. Patients underwent clinical and radiological evaluation every three months. Toxicity was graded using CTCAE v5.0. Dosimetric parameters for the spinal cord (SC), cauda equina (CE), planning organ-at-risk volumes (PRV), and thecal sac were converted to equivalent dose in 2 Gy fractions (EQD₂) using the linear–quadratic model (α/β = 2). Results: Median follow-up was 10.3 months. Forty lesions (65%) were cervicothoracic and 21 (35%) were lumbosacral. One- and two-year overall survival (OS) were 45% and 29%, respectively, and one- and two-year local control (LC) were 89% and 88%, respectively. Gastrointestinal primary tumors were associated with inferior LC (HR 2.41, 95% CI 1.11–5.23, p = 0.026). Fifteen patients (27%) reported myelitis/neuropathic symptoms during follow-up; four (7%) developed new post-radiation myelitis or neuropathy (RMN) without radiologic progression. Five patients (9%) developed vertebral compression fractures (VCF). Cumulative EQD₂ was not significantly associated with RMN (p = 0.344); all affected patients had thecal sac EQD₂ > 95.5 Gy and relevant nerve roots EQD₂ > 108 Gy. Conclusions: ReSBRT provided a favorable LC with acceptable toxicity. High cumulative dose to the thecal sac and nerve roots may contribute to neurologic toxicity as peripheral nerve injury. Full article

Background: Meralgia paresthetica is a neuropathic pain syndrome caused by compression of the lateral femoral cutaneous nerve (LFCN). While often self-limited, a subset of patients develops persistent symptoms requiring interventional management. Ultrasound guidance has improved accuracy and safety in peripheral nerve blocks, but evidence from Internal Medicine-led procedures remains limited. Methods: We performed a retrospective, observational case series including all patients aged ≥17 years who underwent ultrasound-guided LFCN blocks at Virgen del Rocío University Hospital between 2016 and 2024. Demographic data, comorbidities, procedural details, complications, and clinical outcomes were collected. Symptomatic response and recurrence were assessed descriptively. Results: Eleven patients were included (10 women; median age 56 years). The most frequent comorbidities were obesity (45.5%) and type 2 diabetes mellitus (18.2%). Clinical improvement following LFCN block was achieved in 10 of 11 patients (91%). Three patients (27%) experienced recurrence, with a median time to recurrence of 24 months; two underwent a second successful block, and one showed spontaneous resolution. No major complications occurred, and only one patient developed a mild, self-limited local reaction. Conclusions: Ultrasound-guided LFCN block is a safe, well-tolerated, and highly effective intervention for patients with persistent meralgia paresthetica. Outcomes achieved by an Internal Medicine specialist appear consistent with previously published reports from anesthesiology settings, underscoring the value of point-of-care ultrasound as a practical and precise tool for managing neuropathic pain within Internal Medicine settings. Full article