Advancements in Health Research (#AHRjournal) has the aim to become a world-leading medical journal, initially published on a quarterly basis. It accepts, with an open-access policy, studies by highly ranked scientists worldwide, providing scientific material to a large global audience, and aiming to have an impact on health. The publication of this journal was decided by the Fondazione Paolo Procacci based on a large consensus experienced by the previous editorial initiatives of the Fondazione. Our goal is to make science easily available to all those interested. The ambition of #AHRjournal is to serve and aid in a transformation of society, providing an improved and ethical approach to research on health, with a preferential focus on Pain Medicine and Quality of Life. We would be proud to publish papers that provide a crucial contribution to science and human health. #AHRjournal invites the submission of original content, as well as narrative reviews, systematic reviews, and meta-analyses, which may contribute to advances in medical science and practice. Advancements in Health Research promotes open science and supports the early dissemination of research through recognized preprint platforms, facilitating rapid knowledge sharing within the global health research community.
FROM PHENOTYPE TO GENOTYPE: DO COMT, MTHFR, BDNF, OPRM1, AND HTR2A POLYMORPHISMS CONTRIBUTE TO CHRONIC MUSCULOSKELETAL PAIN?
Background and Aims. This study sought to determine whether functional polymorphisms in COMT, MTHFR, BDNF, OPRM1, and HTR2A are differentially distributed across major chronic musculoskeletal pain phenotypes and whether they are associated with pain severity, fatigue, stress, and disease duration. Methods. In this single-center retrospective observational study, the researchers included 19 adults with chronic musculoskeletal pain lasting more than 3 months. Primary diagnoses were fibromyalgia, myofascial pain syndrome, lumbar disc herniation, and arthritis-related pain. Clinical data (demographics, diagnosis, disease duration, VAS pain/fatigue/stress) were extracted from the records. Genomic DNA was isolated from buccal swabs and genotyped for COMT (rs4680, rs4633, rs4818, rs6269), MTHFR (rs1801133, rs1801131), BDNF rs6265, OPRM1 rs1799971, and HTR2A (rs6311). Nonparametric tests (Kruskal–Wallis, chi-square/Fisher's exact) were applied (p<0.05). Results. Fibromyalgia (n=11) showed the greatest genetic heterogeneity, with COMT and MTHFR intermediate/low-activity genotypes and predominantly AA OPRM1 rs1799971. Myofascial pain syndrome (n=3) displayed a similar “nociplastic” profile with heterozygous COMT and MTHFR and OPRM1 AA. Arthritis and lumbar disc herniation were characterized by preserved MTHFR/BDFN patterns and higher frequencies of OPRM1 rs1799971 AG, suggesting a more nociceptive, opioid-modulated profile. OPRM1 rs1799971 distribution differed significantly across diagnoses (p=0.017), while no SNP showed significant associations with VAS pain, fatigue, or stress. Conclusions. Diagnosis-specific genotype patterns, particularly for OPRM1 rs1799971, support biologically distinct nociplastic versus nociceptive profiles in chronic musculoskeletal pain. Although underpowered for definitive associations, this pilot study illustrates the potential of multimarker genetic panels for mechanism-oriented phenotyping and calls for larger, prospective, multi-omic studies to refine genotype-informed, personalized pain management.
Copyright (c) 2026 The Author(s) https://creativecommons.org/licenses/by-nc/4.0
FUNCTION, SATISFACTION, AND RESPONDER RATES AFTER PULSED RADIO FREQUENCY, CRYOABLATION, AND INTRA-ARTICULAR BOTULINUM TOXIN FOR KNEE OSTEOARTHRITIS: A THREE-ARM TRIAL
Background and Aims. Beyond mean pain scores, functional recovery and clinically meaningful responders are crucial for guiding interventional choices in knee osteoarthritis (KOA). We compared function, satisfaction, analgesic pattern, and ≥30% pain-responder rates after pulsed RF, cryoablation, and intra-articular Botox. Methods. In a three-arm comparative study (Assiut University; March 2023–December 2025), 79 KOA patients received pulsed RF (n=27), cryoablation (n=27), or Botox (n=25) with a 12-month follow-up. Function was assessed by WOMAC (baseline, 1, 3, 6, and 12 months) and the Lequesne index (baseline, 3, 6, and 12 months). Satisfaction (4-point Likert) was recorded at 3, 6, and 12 months. Responders were defined as ≥30% VAS improvement from baseline. Results. Functional outcomes improved most with Botox (WOMAC ≈ 26.7–30.0 at 1–12 months), with lower Lequesne scores at 3–12 months (4.10–5.00). Cryoablation showed intermediate early WOMAC improvement versus pulsed RF, with partial loss by 12 months. Satisfaction favored Botox at 3 and 6 months (Likert category 4: 76.0% and 68.0%). Responder rates were highest with Botox across timepoints (72–88%). Cryoablation exceeded pulsed RF early (55.6–74.1% vs. 25.9%) but declined to 0% at 12 months. Conclusions. Botox provided the most durable functional improvement, patient satisfaction, and clinically meaningful responder rates. Cryoablation delivered strong short-term benefit but limited durability, while pulsed RF showed lower responder proportions.
WOUND PAIN ASSESSMENT AND NEGATIVE PRESSURE WOUND THERAPY COMPETENCY GAP IN ITALIAN COMMUNITY NURSES: A CROSS-SECTIONAL MIXED-METHODS STUDY
Background and Aims. Negative pressure wound therapy (NPWT) requires pain monitoring as a critical management dimension, yet Italian nurses show low NPWT-specific self-knowledge (Krówczynska et al., IJERPH 2023; PMID 36834085; N = 401) and significant geographic training disparities—33.3% of Southern Italian nurses received zero wound care training (Ielapi et al., Nurs Rep 2022; PMID 35893640). No Italian study has specifically measured wound pain assessment practices alongside NPWT competency. This study characterizes wound pain assessment practices and NPWT-related pain monitoring competency in Italian community nurses. Methods. Cross-sectional mixed-methods study. Phase 1: Online survey of community nurses (N=41 completed, target N=120; ASL Bari coordination and FNOPI network) using the adapted NPWT Perception Questionnaire (Krówczynska 2023) supplemented with pain-specific items (NRS applicability, procedural pain protocols, and analgesic documentation). Phase 2: three focus groups of N=6 nurse managers each (N=18 total; first group completed; thematic analysis in progress). IRB approval: ASL Bari. Results. Preliminary survey (N=41): 73.2% report no standardized wound pain protocol; 61.0% never used a validated pain scale in wound care; 87.8% received no pain management content in NPWT CPD. First focus group (N=6): wound dressing pain underdocumented as a recurring pattern due to time constraints and absent institutional protocols. Conclusions. Wound pain assessment is a critical competency gap in Italian community NPWT nursing. A structured pain monitoring protocol integrated within NPWT governance frameworks is the evidence-based response to this gap and to Law 38/2010 obligations.
MICROBIAL DRIVERS OF PAIN IN ANKYLOSING SPONDYLITIS: THE ROLE OF INFECTIONS AND GUT MICROBIOME DYSBIOSIS
Background and Aims. Pain is the predominant disabling symptom in ankylosing spondylitis (AS). Emerging evidence suggests that occult infections and intestinal dysbiosis may enhance nociceptive pathways through systemic inflammation and gut-joint immune interactions. This study investigated the association between infectious triggers, gut microbiota alterations, and pain intensity in AS patients. Methods. A cross-sectional case-control study included 316 AS patients and 124 healthy controls. Pain intensity was assessed using VAS alongside BASDAI, BASFI, and ASDAS-CRP. Infectious pathogens were detected by PCR, and gut microbiota composition was analyzed using 16S rRNA sequencing with diversity and machine-learning analyses. Results. AS patients exhibited a high pain burden (mean VAS 5.98±1.45) accompanied by elevated disease activity (mean BASDAI 5.8±1.4). At least one infectious trigger was detected in 50.9% of patients, most commonly Chlamydia trachomatis (21.2%), which was associated with a higher prevalence of peripheral inflammatory pain. Microbiome analysis demonstrated significant dysbiosis compared with controls (PERMANOVA p 90% specificity). Conclusions. Ankylosing spondylitis pain is influenced not only by structural inflammation but also by microbial-immune interactions involving infections and intestinal dysbiosis. These findings support a gut-joint-pain axis in AS and highlight microbial profiling as a potential tool for understanding pain mechanisms and identifying novel therapeutic targets.
ULTRASOUND TRIAD FOR SUPERIOR CLUNEAL NERVE PAIN
Background and Aims. SCN entrapment is an underrecognized cLBP cause. As direct imaging is limited, US surrogate markers of the biomechanical environment are crucial. We analyzed triad prevalence and correlation with pain intensity. Methods. In this single-center, cross-sectional observational pilot study, we enrolled 12 patients with cLBP (>12 weeks) localized to the SCN distribution and a healthy control group (12). Ultrasound measurements included TLF thickness in longitudinal and transverse planes, TLF convexity loss, iliac crest enthesophytes, and CN. Statistical analyses comprised the Mann-Whitney U test, Fisher exact test, Spearman rank correlation, and multivariate logistic regression. Significance was set at p < 0.05. Results. The ultrasound marker triad (CN, iliac enthesophytes, and TLF thickening > 3 mm) demonstrated high diagnostic specificity: individually, CN were present in 91.7% of patients vs. 8.3% of controls (p = 0.001), iliac enthesophytes in 58.3% vs. 0% (p = 0.005), TLF thickening > 3 mm in 41.7% of patients vs. 0% of controls (p = 0.001), and TLF convexity loss in 100% vs. 75% (p = 0.03). Mean TLF thickness was significantly greater in patients—3.53 ± 0.46 mm longitudinally and 3.42 ± 0.39 mm transversely—compared with controls (2.61 ± 0.28 mm and 2.50 ± 0.32 mm; both p < 0.001). TLF thickness correlated strongly with NPRS (Spearman rho = 0.825; p = 0.001) but not with DN4. Logistic regression demonstrated that the marker triad accounted for 67% of NPRS variance (R² = 0.67). Conclusions. US surrogate markers identify pathological SCN environments. Strong nociceptive pain correlation suggests fascial-muscular biomechanics over direct nerve damage. This non-invasive protocol informs targeted rehab.
CHRONIC PAIN TREATMENT DURING PREGNANCY: NAVIGATING THE EVIDENCE GREY ZONE
Background and Aims. Chronic pain during pregnancy is a significant yet underexplored condition. Low back pain, pelvic girdle pain, neuropathic syndromes, headache, fibromyalgia, and pre-existing chronic pain disorders can considerably impair mobility, sleep, daily functioning, and psychological well-being. Despite this burden, therapeutic decisions remain challenging because maternal needs for symptom control must be balanced against fetal and neonatal safety within a limited and often inconsistent evidence base. This review aims to provide a clinically oriented overview of the main evidence gaps affecting the pharmacological management of chronic pain during pregnancy and to highlight key priorities for future research. Methods. We performed a narrative review of the existing literature on pharmacological treatment of chronic pain during pregnancy, focusing on five key areas: the availability of pregnancy-specific data, pharmacokinetic evidence, maternal-fetal safety, long-term outcomes for offspring, and the methodological consistency of published studies and recommendations. Results. Current evidence remains fragmented, heterogeneous, and often indirect. Pharmacokinetic data in pregnant women are limited, long-term neurodevelopmental outcomes are inadequately defined for many common analgesic or adjuvant drugs, and reported endpoints differ significantly across studies. As a result, many treatment decisions are based on extrapolation from non-pregnant populations, trimester-specific precautions, and individualized clinical judgment rather than solid pregnancy-specific guidance. This uncertainty may lead to both the undertreatment of disabling pain and excessive caution in therapy. Conclusions. Treatment of chronic pain during pregnancy remains an area with limited evidence. There is an urgent need for prospective studies, standardized maternal and fetal outcome measures, and pregnancy-specific, clinician-focused guidelines to promote safer and more personalized pain management.
RESULTS OF TRANSVERSUS ABDOMINIS PLANE BLOCK AS A COMPONENT OF MULTIMODAL ANALGESIA IN LIVING LIVER DONORS
Background and Aims. Postoperative pain in living liver donors contributes to surgical stress, opioid use, and delayed recovery. The aim of the study was to assess the effectiveness of transversus abdominis plane (TAP) block within multimodal analgesia in living liver donors. Methods. In a prospective study of 80 donors (age 34.7±6.2 years; BMI 24.6±2.8 kg/m²), 40 received bilateral ultrasound-guided TAP-block with 0.25% bupivacaine (50 mL total) plus dexketoprofen and paracetamol, while 40 received systemic analgesia (NSAIDs + opioids as needed). The groups were comparable in age, sex, BMI, duration of surgery (312±48 vs. 318±51 min), and intraoperative blood loss (420±110 vs. 445±120 mL) (p>0.05). Pain intensity was assessed using the VAS at 2, 6, 12, 24, and 48 hours postoperatively. Pain (VAS), opioid consumption, hemodynamics, metabolic parameters, recovery profile, ICU stay, and PONV were evaluated. Results. The TAP block significantly reduced pain scores at 6, 24, and 48 hours (all p<0.001) and decreased opioid consumption by more than threefold (6.4±3.1 mg vs 18.7±5.6 mg; p<0.001), with opioids required in 27.5% of patients compared to 82.5% (p<0.001). Donors with TAP block showed lower heart rate and blood glucose; earlier mobilization (18.3±4.2 vs 27.6±5.1 h; p<0.001); faster bowel recovery (22.5±6.4 vs 32.8±7.2 h; p<0.001); shorter ICU stay (2.1±0.6 vs 3.4±0.9 days; p<0.001); and lower PONV incidence (15% vs 42.5%; p=0.01). Lactate, transaminases, bilirubin, and INR were significantly lower, indicating reduced metabolic stress and better early liver function. No TAP-related complications occurred. Conclusions. TAP block in living liver donors significantly reduces postoperative pain and opioid use, attenuates the stress response, and accelerates recovery.
CHRONIC PAIN PREVALENCE AND ASSESSMENT GAP IN ITALIAN PUA/UVM PATIENTS: A CROSS-SECTIONAL STUDY
Background and Aims. Chronic pain (CP) affects 24.1% of Italian adults (Violini et al., Pain Res Manag 2025; DOI:10.1155/prm/3401242), yet 86.2% remain unaware of pain management centers. The IFoC (Infermiere di Famiglia o Comunità), mandated by DM 77/2022 with approximately 3,000 patients per nurse, conducts routine multidimensional assessments in U.O. PUA/UVM yet lacks standardized pain assessment protocols. This study quantifies chronic pain prevalence, severity, and functional impact in the PUA/UVM population and maps current IFoC pain assessment practices. Methods. Cross-sectional observational study. Phase 1: consecutive patients referred to U.O. PUA/UVM ASL Bari (N=32 completed, target N=120) administered the NRS and the interview-administered Brief Pain Inventory Short Form (BPI-SF; Cleeland & Ryan, Ann Acad Med Singap 1994; PMID 8080219; validated for chronic nonmalignant pain: Cronbach α=0.85–0.88) during routine multidimensional assessment visits. DN4-interview administered to patients with NRS ≥ 4 to screen for the neuropathic component. Phase 2: semi-structured interviews with IFoC (N=8). IRB waiver for anonymized data; Phase 2 ethics pending. Results. In Phase 1 preliminary results (N=32), 56.3% of patients experienced moderate-to-severe pain (NRS ≥ 4), no patients had a documented pain management plan, and BPI-SF severity and interference data are currently under analysis. Phase 2 (N=8 IFoC): Pain assessment was absent from the standard multidimensional evaluation protocol in all cases; zero had received pain assessment training in the past 3 years. Conclusions. Chronic pain is highly prevalent but unassessed in the PUA/UVM population. Standardizing interview-administered BPI-SF and NRS within the IFoC multidimensional evaluation is a low-cost, evidence-based intervention to close Italy's chronic pain assessment gap.
THORACOLUMBAR JUNCTION SYNDROME AS AN UNDERRECOGNIZED SOURCE OF PELVIC AND HIP PAIN: DIAGNOSTIC AND THERAPEUTIC IMPLICATIONS
Background and Aims. Chronic pelvic and hip pain is frequently attributed to lumbar or intra-articular hip disorders, while the thoracolumbar junction (T11–L2) remains underexplored as a potential pain generator. Thoracolumbar junction syndrome (TLJS), originally described by Maigne, may produce referred pain mimicking hip or visceral pathology. The aim of this study was to analyze diagnostic features and therapeutic outcomes associated with TLJS in patients with chronic lumbopelvic pain. Methods. A narrative review of the literature published between 2013 and 2025 was conducted, integrating clinical studies, case series, and randomized controlled trials focusing on TLJS. Diagnostic criteria included Maigne’s clinical tests (pinch-roll test and segmental palpation). Pain intensity and disability were assessed using the Numerical Rating Scale (NRS) and the Oswestry Disability Index (ODI). Therapeutic interventions included manual therapy targeting the thoracolumbar junction, motor control exercises, and thoracic mobility training. Results. Across the analyzed studies, patients presenting with hip or iliac crest pain and negative local orthopedic tests frequently showed positive TLJ clinical signs. Spine-directed treatment resulted in significant symptom improvement, with mean NRS scores decreasing from 6–7 to near-minimal values and ODI reductions of up to 40–45% within four weeks. Multimodal rehabilitation approaches demonstrated superior outcomes compared to local or symptom-based treatments alone. Conclusions. Thoracolumbar junction syndrome represents a frequent but underdiagnosed cause of pelvic and hip pain. Systematic assessment of the thoracolumbar junction should be integrated into the clinical evaluation of patients with unexplained lumbopelvic pain. Targeted manual and rehabilitative interventions appear effective in reducing pain and disability, potentially preventing misdiagnosis.
METABOLIC DYSFUNCTION AS A REVERSIBLE DRIVER OF SMALL FIBER NEUROPATHY: A CASE REPORT
Background and Aims. Small fiber neuropathy (SFN) is characterized by neuropathic pain with frequently normal nerve conduction studies, which often leads to diagnostic delays and challenges in identifying underlying etiologies. Emerging evidence suggests that metabolic disturbances, including dysglycemia and insulin resistance, may contribute to the development of SFN even in the absence of overt diabetes. Methods. Case Presentation: A 36-year-old male presented with chronic neuropathic pain predominantly affecting the lower extremities in a length-dependent distribution. The DN4 questionnaire score was 7/10, consistent with neuropathic pain. Initial treatment with pregabalin 75 mg twice daily provided only partial relief. Over a three-year period, symptoms progressed to generalized neuropathic pain accompanied by fatigue, cognitive complaints, dyspepsia, and decreased quality of life. Neurological examination revealed reduced pinprick sensation without motor deficits or allodynia. Electromyography of the lower limbs was normal. A skin biopsy with immunohistochemical analysis demonstrated reduced intraepidermal nerve fiber density, confirming the diagnosis of small fiber neuropathy. Comprehensive metabolic evaluation revealed dysglycemia characterized by hyperinsulinemia during oral glucose tolerance testing (fasting insulin 12 μU/mL; 2-hour insulin 229 μU/mL) without meeting criteria for diabetes mellitus. Nutritional assessment suggested deficiencies in alpha-lipoic acid, vitamin B1, and vitamin B3, along with suspected gluten sensitivity. Intervention: A multimodal therapeutic strategy was implemented, including lifestyle modification, a paleo-based elimination diet, and targeted nutraceutical supplementation. Alpha-lipoic acid 600 mg twice daily was prescribed for three months alongside correction of micronutrient deficiencies. Results. After three months of treatment, the patient reported approximately an 80% reduction in neuropathic pain intensity, which allowed for a progressive reduction in pregabalin therapy. At the six-month follow-up, complete resolution of neuropathic pain was reported. Metabolic parameters improved significantly, with fasting insulin decreasing to 3.2 μU/mL and 2-hour insulin to 105 μU/mL. Conclusions. This case highlights metabolic dysfunction as a potentially reversible contributor to small fiber neuropathy. Systematic metabolic and nutritional evaluation may help identify modifiable etiologies in patients with unexplained neuropathic pain. Targeted lifestyle and metabolic interventions may lead to substantial clinical improvement and even symptom resolution.
LAW 38/2010 AND COMMUNITY NURSING: THE IFOC/IFEC AS MISSING GATEWAY TO ITALY'S PAIN THERAPY NETWORK
Background and Aims. Italy's Law 38/2010 established citizens' right to access palliative care and pain therapy as essential levels of care. Fourteen years later, Violini et al. (Pain Res Manag 2025; DOI:10.1155/prm/3401242) confirm this landmark law has produced very few achievements for the real benefit of relieving chronic pain in the population compared with expectations. The IFoC (Infermiere di Famiglia o Comunità), mandated by DM 77/2022 with approximately 3,000 patients per nurse, is strategically positioned to function as the missing gateway between citizens and the pain therapy network. This study aims to assess whether IFoC systematically identify and refer chronic pain patients to Law 38/2010 network centers in Bari province. Methods. Mixed-methods implementation study. Phase 1: retrospective audit of U.O. PUA/UVM referral records (January–December 2025; target N=200 multidimensional assessments): extraction of pain-related documentation, NRS recording, and pain center referrals generated. Phase 2: semi-structured interviews with IFoC (N=15, ASL Bari) and MMG (N=10) on awareness of the local Law 38 network and referral practice barriers. Ethical approval: ASL Bari IRB Results. Preliminary audit (N=58 records): pain documentation present in 29.3%; NRS recorded in 15.5%; referral to the pain network under Law 38/2010 generated in 3.4%. IFoC interviews (N=8): 62.5% were unaware of local pain therapy center contacts; zero had received Law 38 training in the past 3 years. Conclusions. The IFoC is the closest professional to the chronic pain patient yet remains structurally disconnected from Italy's pain therapy network. A structured Law 38/2010 integration protocol within DM 77/2022 territorial care frameworks is urgently needed.
INTESTINAL FUNGAL DYSBIOSIS AS A POTENTIAL CONTRIBUTOR TO CHRONIC LOW BACK PAIN: A CASE SERIES
Background and Aims. Chronic low back pain is a leading cause of disability worldwide and is commonly attributed to structural or degenerative spinal conditions. However, in many patients imaging findings do not fully explain symptom severity. Emerging evidence suggests that alterations in the gut microbiome may contribute to systemic inflammation and chronic pain states through mechanisms involving immune activation and gut barrier dysfunction. Methods. Case Presentation We report four female patients with chronic low back pain of unclear structural etiology who also presented with gastrointestinal symptoms including bloating, dyspepsia, abdominal discomfort, and altered bowel habits. All patients had persistent lumbar pain despite conventional management, including analgesics, physical therapy, and spinal interventional procedures such as lumbar facet or epidural blocks. Imaging findings demonstrated mild or nonspecific degenerative changes insufficient to explain the severity of symptoms. Microbiome and gastrointestinal evaluations revealed intestinal dysbiosis in all cases. Case 1: Mixed dysbiosis characterized by Helicobacter pylori infection, Candida overgrowth, increased pathogenic and commensal bacterial flora, IgA deficiency, and hypochlorhydria. Case 2: Stool microbiome analysis revealed mixed dysbiosis with a Dysbiosis Index of 3, decreased butyrate-producing bacteria, reduced butyrate percentage (10%), elevated fecal calprotectin (102 μg/g), and acidic stool pH (5.5), consistent with low-grade intestinal inflammation and impaired gut barrier function. Culture demonstrated overgrowth of imbalanced bacterial flora, and microscopy reported moderate yeast. Cases 3 and 4: Stool analysis reported only scarce yeast; however, both patients presented with marked gastrointestinal symptoms suggestive of fungal dysbiosis, accompanied by bacterial microbiome imbalance. Intervention. All patients underwent a microbiome-directed therapeutic protocol including an elimination diet, antifungal therapy when indicated, and microbiome-supportive supplementation aimed at restoring intestinal microbial balance and gut barrier function. Results. Gastrointestinal symptoms began to improve around the third week of treatment in all patients. Improvement in lumbar pain occurred simultaneously with the relief of gastrointestinal symptoms. Pain intensity progressively decreased, with complete remission of lumbar pain occurring between weeks 6 and 8. Follow-up at one year demonstrated sustained remission of low back pain, persistent functional improvement, and no recurrence of symptoms. Conclusions. This case series suggests that intestinal dysbiosis, including bacterial imbalance and fungal overgrowth, may represent an underrecognized contributor to chronic low back pain in selected patients. Evaluation of the gut microbiome may provide valuable diagnostic insights in individuals whose symptoms are not fully explained by structural spinal pathology. Clinicians should consider the possibility of microbiome-related pain mechanisms in patients presenting with diffuse or multisite pain, lumbar allodynia, and systemic symptom clusters, particularly when accompanied by complaints affecting multiple systems such as headache, cognitive impairment (“brain fog”), nasal pruritus, or gastrointestinal disturbances. These findings support the emerging concept of a gut–spine axis in chronic pain syndromes and suggest that microbiome-directed interventions may represent a promising therapeutic strategy. Further controlled studies are warranted to clarify this relationship.
SPECIFICITY OF PAIN PERCEPTION AND REPORTING IN OLDER ADULTS: A RETROSPECTIVE STUDY
Background and Aims. Pain in older adults is frequently underreported and misinterpreted as a natural consequence of aging, potentially leading to inadequate management. An evaluation of the determinants of pain perception and reporting among older adults, with particular emphasis on psychological, cognitive, and personal factors. Methods. A cross-sectional study was conducted in 212 adults aged ≥65 years recruited from outpatient clinics. Pain intensity was assessed using the Numerical Rating Scale, while pain characteristics were evaluated using the Brief Pain Inventory. Cognitive status was assessed using the Mini-Mental State Examination. Sociodemographic and clinical data were collected through structured interviews. Multivariable linear regression analysis was performed to identify factors associated with self-reported pain intensity, and Spearman correlation analysis was used to assess relationships between psychological variables and pain scores. Descriptive analyses were used to summarize the prevalence of chronic pain. Results. Chronic pain was reported by 58% of participants, with higher prevalence in institutionalized individuals (76% vs. 49%, p < 0.01). Lower pain intensity was associated with male gender (β = -0.28, p = 0.02), lower catastrophizing scores (β = -0.34, p < 0.01), and reduced cognitive function (MMSE < 24; β = -0.31, p = 0.01). Higher self-efficacy was moderately correlated with lower pain intensity (r = -0.42, p < 0.001). Conclusions. A complex interplay of psychological, cognitive, and sociocultural factors influences pain perception and reporting in older adults. Lower reported pain intensity is more common among men and individuals with cognitive impairment, which may contribute to underrecognition of pain in these groups. These findings emphasize the necessity of structured and multidimensional pain assessment strategies among people over 65.
TRANSARTERIAL EMBOLIZATION FOR CHRONIC SHOULDER TENDINOPATHY AND BURSITIS: EARLY CLINICAL OUTCOMES USING DEGRADABLE STARCH MICROSPHERES
Background and Aims. The aim of this study is to evaluate the clinical effectiveness and safety of transarterial embolization (TAE) with degradable starch microspheres (EmboCept®) in patients with chronic shoulder tendinopathy/bursitis refractory to conservative therapy. Methods. This prospective single-center study (July - December 2025) included 10 consecutive patients (6 women, 4 men; mean age 66.3 ± 15.6 years) with unilateral shoulder tendinopathy/bursitis treated with TAE. Laterality was left in 7 and right in 4 cases. All procedures used EmboCept® degradable starch microspheres. Clinical outcome was assessed with the Shoulder Pain and Disability Index (SPADI) at baseline, 48 hours, 3 months, and 6 months when available. Descriptive statistics were calculated for available follow-ups. Results. The mean baseline SPADI was 96.3 ± 30.1 (n = 11). At 48 hours (n = 10), mean SPADI decreased to 37.1 ± 35.0, corresponding to a 61% relative improvement. At 3 months (n = 8), mean SPADI was 42.4 ± 34.5 (56% relative improvement vs. baseline). One patient had 6-month follow-up (SPADI 31). Most patients demonstrated rapid early pain and disability reduction; however, variability at 3 months was observed, including one case with clinical worsening (SPADI 100). No major complications were recorded in the dataset. Conclusions. TAE with degradable starch microspheres for chronic shoulder tendinopathy/bursitis appears technically feasible and is associated with substantial early SPADI improvement, with maintained benefit at 3 months in most patients. Outcomes show inter-individual variability, emphasizing the necessity of larger prospective studies with standardized imaging selection and complete follow-up to define durability and predictors of response.
THE EFFECT OF STELLATE GANGLION BLOCK ON DEPRESSION IN PATIENTS WITH IDIOPATHIC SUDDEN HEARING LOSS
Background and Aims. Stellate ganglion block (SGB) is useful to treat idiopathic sudden hearing loss (ISHL) by enhancing cochlear perfusion. Recently, SGB has been reported to improve depression in post-traumatic stress disorder. But it remains unclear whether SGB can decrease depression in patients with ISHL. Methods. In this retrospective observational study, 35 patients with ISHL were included. Dexamethasone 10 mg was injected once daily for 5 days, followed by 5 mg once daily for an additional 5 days. Patients received SGB every other day for 10 days. SGB was performed 2 hours before dexamethasone treatment. Depressive symptoms were assessed using the Beck Depression Inventory (BDI) and Generalized Anxiety Disorder-7 (GAD-7) before (baseline) and 1 day and 30 days after treatment. Pure-tone audiometry (PTA) was evaluated before and 30 days after treatment. Results. PTA improved at 30 days after treatment (47.9 ± 27.7), compared to baseline (68.0 ± 23.2) (P < 0.001). The BDI significantly decreased at 1 day (5.5±8.0) and 30 days (4.5±7.4) after treatment, compared to baseline (9.1±8.2) (P<0.0001). The GAD-7 decreased at 1 day (2.3 ± 3.0) and 30 days (1.9 ± 2.6) after treatment, compared to baseline (4.7 ± 3.6) (P < 0.0001). However, improvement in PTA is not correlated with improvements in BDI or GAD-7. Conclusions. SGB significantly decreases depressive symptoms in patients with ISHL, which is not correlated with the degree of hearing recovery. These findings suggest that SGB provides a beneficial effect for mood improvement in this population.
SEVERE PAIN AND NEUROLOGICAL SYMPTOMS AS AN INITIAL MANIFESTATION OF PARANEOPLASTIC SYNDROME: A CASE REPORT
Background and Aims. Paraneoplastic neurological syndromes (PNS) are rare, affecting less than 1% of patients with malignancy, yet they may precede cancer diagnosis and represent a significant diagnostic challenge. Pain is highly prevalent in oncology, affecting approximately 55% of patients during anticancer treatment and up to 66% in advanced disease. In paraneoplastic neuropathies, pain has been reported as the first manifestation in 41.3% of cases and as the sole initial manifestation in 13.0%. Methods. A 63-year-old female patient presented with recurrent episodes of severe pain accompanied by neurological symptoms, including muscle stiffness and seizure-like episodes. The attacks occurred with very high frequency, at times every 20 minutes, leading to marked functional impairment and deterioration in quality of life. Initial clinical evaluation was inconclusive due to the non-specific presentation, resulting in repeated consultations and diagnostic uncertainty. With disease progression, advanced malignancy of unknown primary origin was diagnosed. The constellation of neurological symptoms and severe, treatment-resistant pain was subsequently recognized as a manifestation of a paraneoplastic syndrome. Despite standard analgesic treatment, pain remained refractory, representing a major therapeutic challenge. Results. This case highlights the diagnostic complexity of paraneoplastic syndromes when pain dominates the clinical picture. Severe, recurrent, and treatment-resistant pain associated with atypical neurological features should prompt consideration of a paraneoplastic etiology. Since PNS may precede oncological diagnosis, delayed recognition may prolong patient suffering and postpone appropriate management. Conclusions. Paraneoplastic syndromes may present with severe refractory pain and neurological symptoms before malignancy is diagnosed. Increased clinical awareness of such presentations is essential to reduce diagnostic delay and improve patient management.
OPIOID-SPARING EFFECT OF LIDOCAINE, KETAMINE AND MAGNESIUM IN THORACOTOMY
Background and Aims. Thoracotomy is associated with severe postoperative pain and high opioid requirements. Perioperative pain management increasingly prioritizes opioid-sparing strategies that maintain effective analgesia. This study evaluated whether intraoperative lidocaine–ketamine–magnesium (LKM) infusion reduces postoperative morphine consumption and pain intensity. Methods. A prospective single-center observational study included 118 adult patients undergoing pulmonary resection via thoracotomy. Patients received either intraoperative LKM infusion as part of a multimodal analgesic protocol or standard perioperative analgesia. The primary outcome was cumulative morphine consumption during the first 24 postoperative hours. Secondary outcomes included pain intensity measured with the Visual Analogue Scale (VAS) at 3 and 24 hours, the prevalence of chronic pain at 3 months, and drug-related adverse events. Multivariable regression analysis assessed the independent association between LKM administration and morphine consumption. Results. Morphine consumption during the first 24 postoperative hours was significantly lower in the LKM group compared with controls (median [IQR] 2 [0–6] mg vs. 5 [3–8] mg; p = 0.001), representing an approximate 60% reduction in morphine consumption. After multivariable adjustment, LKM administration remained independently associated with reduced morphine consumption (β = −1.76; 95% CI −3.40 to −0.12; p = 0.03). Pain scores were significantly lower at 3 and 24 hours postoperatively. No differences were observed in the prevalence of chronic pain at 3 months and no drug-related adverse events occurred. Conclusions. Intraoperative lidocaine–ketamine–magnesium infusion improves early postoperative analgesia and reduces morphine consumption after thoracotomy. Further studies are needed to confirm these findings.
PAIN AS A NEUROCARDIAC STRESSOR: REFRAMING PAIN BEYOND NOCICEPTION
Background and Aims. Pain is usually considered a sensory and emotional experience. However, growing evidence shows that pain also triggers integrated neuroendocrine and autonomic responses with broad effects. Through the brain–heart axis, both acute and chronic pain can act as biological stressors that impact cardiovascular health, regardless of how pain is perceived. The aim is to develop a clinically focused conceptual framework that describes pain as a neurocardiac stressor and highlights its possible role as a systemic disease modifier. Methods. We conducted a narrative, mechanism-focused synthesis of current evidence on pain-related activation of the hypothalamic–pituitary–adrenal (HPA) axis, autonomic imbalance, and downstream cardiovascular effects, with an emphasis on clinically relevant pathways. Results. Pain triggers a coordinated stress response involving activation of the limbic system, hypothalamic signaling, and engagement of the HPA axis, resulting in cortisol release and dominance of sympathetic activity. This autonomic imbalance is linked to decreased vagal tone, reduced heart rate variability, and elevated catecholamine levels. The downstream effects include endothelial dysfunction, microvascular impairment, pro-inflammatory signaling, and increased myocardial oxygen demand. These mechanisms may contribute to arrhythmogenic vulnerability, hemodynamic instability, and stress-related cardiomyopathy. Importantly, persistent pain can sustain these pathways over time, indicating a role as a chronic systemic stressor. Conclusions. Pain should be viewed as more than just a symptom; it acts as a neurocardiac stressor with possible systemic effects. Incorporating pain assessment into cardiovascular risk evaluation and adopting a brain–heart approach could lead to new opportunities in both clinical management and translational research.
RADIOFREQUENCY DENERVATION IN THE MANAGEMENT OF SACROILIAC JOINT PAIN: A COMPARATIVE STUDY OF TWO TECHNIQUES
Background and Aims. Sacroiliac joint (SIJ) dysfunction is a significant source of chronic low back pain, affecting 10% to 25% of patients. When conservative treatments fail, radiofrequency (RF) denervation is a common second-line intervention. This study aims to evaluate the efficacy of RF denervation in SIJ dysfunction and to compare the clinical efficacy and operational efficiency of two different RF techniques: the monopolar clock technique and the bipolar palisade technique. Methods. A retrospective observational study was conducted on 81 patients who underwent RF for SIJ dysfunction: 35 underwent monopolar clock RF and 46 underwent bipolar palisade RF. We collected NRS, BPI (BPI_DOL and BPI_QUAL), and opioid consumption at baseline and in the follow-up at 1, 3, and 6 months after the procedure. Operational parameters, including fluoroscopy time and the number of shots, were also recorded. Results. Both techniques significantly reduced pain and opioid use by over 30% at the 6-month follow-up, with no statistically significant difference between groups. However, the bipolar palisade technique demonstrated superior operational efficiency, requiring significantly shorter fluoroscopy times and fewer shots. Conclusions. Radiofrequency denervation is highly effective for the mid-to-long-term management of SIJ pain. While both techniques provide comparable clinical relief at 6 months, the bipolar palisade technique is more efficient by reducing radiation exposure for both patients and operators.
WOUND PAIN ASSESSMENT IN ITALIAN DOMICILIARY PALLIATIVE CARE: AN AUDIT OF LAW 38/2010 COMPLIANCE IN HOMENURSING
Background and Aims. Law 38/2010 guarantees access to palliative care and pain therapy in all settings, including home care. Chronic wound pain — prevalent in pressure injuries, diabetic foot ulcers, and vascular ulcers — is a cardinal palliative symptom in end-of-life patients. Italian nurses in palliative home care report feeling "alone during emergencies and sensitive communications" and identify inadequate training as a primary challenge (Iotti et al., PMC 2025; N=39 nurses, Reggio Emilia). No Italian study has assessed wound pain assessment competency specifically in home-based palliative nursing. This study aims to quantify the wound pain assessment gap in palliative care nursing for Italian patients at home. Methods. Sequential mixed-methods. Phase 1: retrospective audit of palliative home care records in ASL Bari U.O. Cure Palliative Domiciliari (N=60 patients, January–March 2026): wound pain documentation frequency, validated scale use (NRS, PAINAD, and Edmonton Symptom Assessment Scale), and analgesic adequacy (Pain Management Index). Phase 2: focus groups with palliative home care nurses (N=12, ASL Bari) on wound pain barriers. Ethical approval: ASL Bari IRB. Results. Preliminary audit (N=22 records): wound pain formally assessed in 31.8%; PAINAD or ESAS used in 9.1%; Pain Management Index negative (undertreated) in 63.6%. Focus group preliminary findings: wound pain perceived as "minor" compared to disease pain by 83.3% of nurses interviewed. Conclusions. Wound pain in Italian domiciliary palliative care is systematically underassessed and undertreated. Integrating structured wound pain protocols into Law 38/2010 palliative home care pathways is an urgent, measurable imperative for patient dignity.
THE EFFECT OF MULTIMODAL ANALGESIA ON INTRA-ABDOMINAL PRESSURE AND CLINICAL OUTCOMES IN PATIENTS WITH INTRA-ABDOMINAL HYPERTENSION SYNDROME
Background and Aims. In patients with intra-abdominal hypertension (IAH), inadequate analgesia enhances sympathetic activation, increases intra-abdominal pressure (IAP), and exacerbates organ dysfunction. The aim of the study was to assess the effectiveness of multimodal analgesia on IAP and clinical outcomes in patients with IAH. Methods. In a prospective study of 84 patients (age 52.5±13.4 years) with grade I–III IAH, 44 received continuous epidural analgesia with 0.2% ropivacaine/fentanyl and Dexketoprofen (Dexalgin), while 40 received systemic opioid analgesia plus NSAIDs. The main causes of IAH were abdominal sepsis (34.5%), acute pancreatitis (27.4%), major abdominal surgery (23.8%), and polytrauma (14.3%). IAP, abdominal perfusion pressure (APP), pain intensity (VAS), opioid requirements, SOFA-score, duration of mechanical ventilation (MV), and ICU length of stay were assessed. Results. In the main group after 24 hours, IAP decreased from 18.6±3.4 to 13.2±2.8 mmHg versus a decrease from 18.9±3.1 to 16.1±3.0 mmHg in the comparison group (p<0.001). APP increased to 72±9 mmHg versus 63±8 mmHg in the comparison group (p=0.002). Pain scores on the VAS were lower (3.1±1.0 vs 5.4±1.3; p<0.001), and daily opioid requirements were reduced (12.5±4.2 vs 28.7±6.5 mg morphine equivalents; p<0.001). Organ dysfunction according to the SOFA score regressed more rapidly (decrease of 3.2±1.1 points vs. 1.4±0.9; p=0.003). The duration of MV was 3.8±1.7 vs 5.6±2.4 days (p=0.01), and ICU stay was 6.5±2.3 vs 9.2±3.1 days (p=0.004). Conclusions. In patients with IAH, multimodal analgesia significantly reduces IAP, increases APP, decreases opioid consumption, and accelerates the regression of SOFA-score. Optimized analgesia should be considered an essential component of comprehensive IAH management.
ULTRASOUND-GUIDED CRYONEUROLYSIS: A NOVEL APPROACH TO PAIN MANAGEMENT IN RHEUMATOID ANKLE AND FOOT ARTHRITIS
Background and Aims. Rheumatoid arthritis (RA) is a systemic autoimmune disease that frequently affects the foot and ankle. More than 90% of patients develop symptoms in these regions during the course of the disease, leading to pain, deformity, and disability. Chronic ankle and foot pain in RA may persist despite pharmacological and surgical interventions, severely impairing daily activities and professional duties. This case report aims to demonstrate the efficacy of ultrasound‑guided cryoneurolysis in refractory RA‑related ankle and foot pain, emphasizing its impact on pain relief, functional recovery, and preservation of gait and proprioception. Methods. A 45-year-old female pediatric physician with a 15-year history of rheumatoid arthritis and prior subtalar and talo-navicular arthrodesis presented with severe chronic left ankle and foot pain (VAS 10/10). Over five years, she received multiple systemic and local therapies, including NSAIDs, gabapentin, pregabalin, duloxetine, intra-articular steroids, hyaluronic acid, ozone, botulinum toxin, and rehabilitation modalities, without improvement. Prior to definitive cryoneurolysis, an ultrasound-guided (USG) diagnostic block was performed targeting the superficial fibular, sural, saphenous, and deep peroneal nerves, resulting in >90% pain relief that was sustained for 24 hours. On August 17, 2025, USG cryoneurolysis was subsequently carried out on the same nerves. Results. The procedure resulted in immediate and complete pain relief (VAS 0/10). The patient resumed activities of daily living and professional work without limitations. Importantly, gait and proprioception were not affected. Pain relief persisted for six months, with no reported complications. Conclusions. Ultrasound-guided cryoneurolysis of ankle nerves is a safe and effective minimally invasive option for refractory RA-related ankle and foot pain. This case demonstrates sustained analgesia, functional recovery, and preservation of gait and proprioception, underscoring its potential role in patients unresponsive to conventional therapies
Background and Aims. Overlapping chronic pain conditions (OCPCs) are increasingly recognized in patients with rheumatic diseases, potentially influencing disease assessment and treatment decisions. To evaluate the prevalence and impact of OCPC in rheumatic patients. Methods. We conducted an observational study including 150 patients, divided equally into rheumatoid arthritis (RA) (n=50), systemic lupus erythematosus (SLE) (n=50), and systemic sclerosis (SSc) (n=50) groups. OCPCs were identified based on clinical evaluation and patient-reported pain characteristics. Disease activity scores and treatment requirements were compared between patients with and without OCPC. Results. OCPCs were identified in 36 patients (24%): RA 12/50 (24%), SLE 16/50 (32%), and SSc 8/50 (16%). In RA, fibromyalgia (58.3%) and chronic low back pain (33.3%) predominated. In SLE, fibromyalgia (50%), chronic headache (37.5%), irritable bowel syndrome–related pain (31.3%), and chronic pelvic pain (18.8%) were common, with multiple overlapping conditions frequent. In SSc, musculoskeletal pain (50%), fibromyalgia-like pain (37.5%), and headache (25%) were observed. Patients with OCPC exhibited higher disease activity scores: RA DAS28 5.1 ± 0.8 vs 3.8 ± 0.7, SLE SLEDAI 12.4 ± 3.1 vs 8.6 ± 2.9, and SSc mRSS 18.2 ± 4.5 vs 13.1 ± 3.8. Intensified immunosuppressive therapy was required in 69.4% of patients with OCPC versus 36.0% without. Conclusions. OCPC are common in rheumatic diseases, linked to higher disease activity and greater therapy needs, highlighting the risk of misattributing pain to inflammation and the need for precise pain phenotyping and multimodal management.
BEYOND ANALGESIA: FASCIAL PLANE BLOCKS AS MODULATORS OF THE SURGICAL STRESS RESPONSE
Background and Aims. Fascial plane blocks are increasingly used as part of multimodal analgesia in perioperative care. While traditionally seen only as pain-relief techniques, their ability to influence the systemic stress response to surgery is still not well understood. Surgical trauma triggers a complex neuroendocrine and inflammatory response, involving sympathetic activation, hypothalamic–pituitary–adrenal (HPA) axis activation, and cytokine release, all of which can affect postoperative recovery and organ function. To create a clinically relevant framework that views fascial plane blocks as modulators of the surgical stress response, beyond their role in pain relief. Methods. We conducted a narrative, mechanism-based review that integrates current evidence on regional anesthesia, autonomic modulation, and perioperative stress physiology, with a focus on fascial plane techniques. Results. By reducing nociceptive input at its source, fascial plane blocks may decrease central sensitization and limit activation of stress-related pathways. This could result in lower sympathetic output, better autonomic balance, and decreased neuroendocrine activation. Emerging evidence suggests potential downstream effects, including reduced catecholamine release, modulation of inflammatory responses, improved hemodynamic stability, and decreased opioid requirements. These mechanisms may help enhance recovery, reduce complication rates, and improve patient-centered outcomes. However, current data are heterogeneous and largely indirect, with few studies specifically evaluating systemic effects. Conclusions. Fascial plane blocks should be viewed not only as pain management tools but also as potential modulators of the surgical stress response. Adopting a broader physiological perspective can facilitate their incorporation into strategies to improve perioperative resilience and recovery.
PROCEDURAL PAIN AND FEAR IN NON-HEALING WOUNDS AFTER STERNOTOMY
Background and Aims. The aim of the study was to investigate procedural pain and pain-related fear during canister exchange in patients with a V.A.C. (Vacuum Assisted Closure) on a sternotomy wound system. Methods. Data collection took place from 5/2025 to 2/2026 at the Department of Cardiac Surgery, Institute of Clinical and Experimental Medicine, in Prague, after approval by the ethics committee. The criteria for inclusion in data collection were adulthood, signed informed consent, knowledge of the Czech language, and first replacement of the V.A.C. canister, which was implanted due to a non-healing wound after sternotomy. The following methods were used: anamnestic data, numerical rating scale (NRS), and adult facial anxiety scale (AFAS, McCormack, 1988). Results. N = 47 patients were examined (mean age M = 65.25, SD = 10.25, 59% men). Patients were at M = 5.17, SD = 24.21 months after the cardiac surgery. According to the intensity of procedural pain, we divided the patients into two groups: G1 mild pain NRS 0-3 (n = 39) and G2 moderate-to-severe pain NRS > 4 (n = 9). The groups significantly differed in the level of fear (AFAS) before and after canister replacement (ps < 0.001). The intensity of procedural pain was moderate before the procedure (rs = -0.322, p = 0.027). Anticipated pain significantly increases the likelihood of moderate to severe procedural pain in our sample (OR = 6.9093, 95% CI: 2.0852–22.8943). Conclusions. It is important to prevent pain-related fear during procedural pain associated with a non-healing sternotomy wound in adults using psychological approaches.
EMERGING DRUGS OF ABUSE IN THE CHRONIC PAIN POPULATION: A CLINICAL PHARMACOLOGY PERSPECTIVE ON KRATOM, NOVEL SYNTHETIC OPIOIDS, DESIGNER BENZODIAZEPINES, GABAPENTINOIDS, XYLAZINE, AND KETAMINE
Background and Aims. Chronic pain patients increasingly self-medicate with unregulated and emerging psychoactive substances, driven by opioid prescribing restrictions, cost barriers, and the widespread perception that "natural" alternatives are safe. Pain specialists face a critical knowledge gap: none of the substances reviewed in this analysis are detectable on standard immunoassay urine drug screens, rendering conventional monitoring strategies fundamentally insufficient for this evolving patient population. The aim is to characterize the pharmacology, clinical risk profiles, drug interaction mechanisms, regulatory status, and toxicological detection requirements of six emerging drug classes of direct relevance to pain medicine practice: kratom (Mitragyna speciosa), novel synthetic opioids (nitazenes), designer benzodiazepines, gabapentinoids (in the context of misuse), xylazine, and ketamine. Methods. Narrative review of published peer-reviewed literature, pharmacovigilance databases, and regulatory agency communications (FDA, DEA, EMCDDA, EMA), supplemented by large-scale survey data. Analysis was conducted from a clinical pharmacology perspective with primary emphasis on patient safety implications for pain medicine practitioners operating in international settings. Results. Kratom, used by an estimated 1.7 billion individuals globally, produces biphasic dose-dependent effects via mu-opioid receptor agonism and CYP3A4/CYP2D6 inhibition, creating clinically silent pharmacokinetic interactions with co-prescribed analgesics. Nitazenes — benzimidazole-class full MOR agonists 10–100× more potent than morphine — are increasingly detected in illicit opioid supplies across North America and Europe and require LC-MS/MS for identification, which is unavailable on standard panels. Designer benzodiazepines (etizolam, clonazolam, and flualprazolam) escape standard immunoassay detection entirely and produce respiratory depression synergistic with prescribed opioids. Gabapentinoid misuse is implicated in over 35% of opioid-related deaths in the United Kingdom. Xylazine adulteration of fentanyl creates a dangerous partial naloxone-response scenario with pathognomonic necrotic wound presentation. Ketamine’s expanding therapeutic use coexists with irreversible uropathy documented in 20–30% of chronic recreational users. Across all six substance classes, standard urine drug screens are uniformly inadequate; targeted confirmatory testing (LC-MS/MS, GC-MS) and specific, non-judgmental patient questioning are required. Conclusions. Emerging drugs of abuse represent a clinically urgent and underrecognized patient safety challenge in pain medicine. Pain specialists must adopt substance-specific screening strategies, update patient communication frameworks, and engage professional societies to address the regulatory and educational gaps the rapidly evolving landscape exposes. Collaborative international pharmacovigilance and sustained research investment are essential to protect patients across jurisdictions.
REGENERATIVE ULTRASOUND-GUIDED PRP PLUS HYALURONIC ACID PROVIDES DURABLE PAIN CONTROL IN KNEE OSTEOARTHRITIS
Background and Aims. Knee osteoarthritis (OA) is a major cause of chronic nociceptive and inflammatory pain. Intra-articular hyaluronic acid (HA) is widely used, but its analgesic effect is often temporary. Platelet-rich plasma (PRP), through growth factor release and modulation of synovial inflammation, may enhance and prolong pain relief. This study aimed to evaluate whether ultrasound-guided PRP combined with high-molecular-weight HA provides superior and sustained analgesia compared with HA alone in patients with knee OA. Methods. In this prospective observational study, 100 patients with MRI-confirmed knee OA (Kellgren–Lawrence II–III) received three ultrasound-guided intra-articular injections at 30-day intervals. Group A received leukocyte-poor PRP plus 60 mg high-molecular-weight HA; Group B received identical HA alone. Pain intensity was assessed using the Numeric Rating Scale (NRS, 0–10) and functional status using WOMAC at baseline, 30 days, 2, 3, 6, and 12 months. Statistical significance was set at p < 0.05. Results. The PRP + HA group demonstrated progressive and sustained analgesia, with mean NRS decreasing from 7.0 at baseline to 2.1 at 12 months (−70%). WOMAC improved from 62 to 24 (−61%). In contrast, the HA-only group showed early transient improvement, with NRS changing from 6.9 to 6.8 at 12 months and WOMAC from 60 to 58. Between-group differences at 6 and 12 months were statistically significant (p < 0.05). Conclusions. Ultrasound-guided PRP combined with high-molecular-weight HA provides clinically meaningful and durable pain reduction compared with HA alone in knee OA, supporting its role in regenerative pain management (see Table below).
NURSE BURNOUT AND THE BIOPSYCHOSOCIAL PAIN ASSESSMENT GAP: A CROSS-SECTIONAL STUDY IN ITALIAN COMMUNITY NURSING
Background and Aims. Chronic pain and psychological comorbidity are bidirectionally linked: 30–50% of chronic pain patients present with concurrent depression and/or anxiety (PHQ-ADS; Kroenke et al., PMC 2016). Nurse burnout impairs clinical judgment across all care domains (Li et al., JAMA Netw Open 2024; N=288,581); yet the specific impact of burnout on biopsychosocial pain assessment—integrating physical and psychological dimensions—remains unmeasured in Italian community nursing. This study examines whether nurse burnout severity predicts failure to screen for psychological pain comorbidity alongside physical pain management adequacy. Methods. Cross-sectional correlational study (PROSPERO pre-registered). Participants: N=150 community nurses, ASL Bari territorial services (COT, Casa della Comunità, PUA/UVM). Instruments: Maslach Burnout Inventory (MBI); record audit — NRS documentation + Hospital Anxiety and Depression Scale (HADS) or PHQ-9 administration rate; Pain Management Index (PMI). Multiple regression: MBI emotional exhaustion → HADS/PHQ-9 administration rate and PMI adequacy simultaneously. Ethical approval: ASL Bari IRB. Results. Preliminary data (N=38 nurses, 760 records): HADS or PHQ-9 administered in 8.2% of chronic pain records. PMI negative (undertreated) in 62.4%. The MBI emotional exhaustion score independently predicted both absent psychological screening (OR=2.1, p=0.004) and PMI negativity (OR=2.3, p=0.002). Conclusions. Burnt-out community nurses simultaneously undertreat physical pain and fail to screen for psychological comorbidity—the double neglect of the biopsychosocial pain model. Systems-level burnout prevention is a multimodal pain management priority with direct policy implications for Italian NHS territorial models.
GUT MICROBIOTA AND PAIN EXPRESSION IN ANKYLOSING SPONDYLITIS: CLINICAL-MICROBIAL CORRELATES (GRASP-STUDY)
Background and Aims. Pain is the dominant clinical manifestation in ankylosing spondylitis (AS), reflecting both structural inflammation and neuroimmune mechanisms. Emerging evidence suggests that gut microbiota dysbiosis may contribute to systemic inflammation and pain amplification. This study aimed to evaluate the relationship between intestinal microbiota composition and pain expression in AS. Methods. A cohort of 60 subjects (41 AS patients, 19 controls) was analyzed. Patients were stratified into axial (axAS) and peripheral (pAS) phenotypes. Clinical data included inflammatory markers and disease activity indices. Pain intensity was assessed indirectly through disease activity parameters. Gut microbiota composition was evaluated using PCR-based analysis, followed by multivariate and classification modeling. Results. AS patients demonstrated a distinct microbial profile compared to controls (p < 0.001), with 12 predominant bacterial species identified versus 8 in controls. A significant reduction in Bacteroides (0.332 vs. 0.430) and marked increase in Prevotella (0.168 vs. 0.031) were observed, indicating dysbiosis associated with inflammatory activation. Patients with peripheral AS exhibited earlier disease onset (18.0 vs 25.5 years; p < 0.01) and higher inflammatory burden, corresponding to increased pain-related clinical expression. Multivariate analysis identified 8 microbial genera (including Dialister, Collinsella, and Streptococcus) as key discriminators of AS, with a classification accuracy of 95%, suggesting strong biological relevance. These taxa are known to induce pro-inflammatory pathways, supporting a mechanistic link between gut dysbiosis and nociceptive sensitization. Conclusions. Gut microbiota alterations are associated with inflammatory activity and pain expression in AS. Microbial profiling may represent a novel biomarker for early identification of high-pain phenotypes and a potential therapeutic target.
GENDER DIFFERENCES IN THE PRESENTATION AND MANAGEMENT OF CHRONIC PAIN: EVIDENCE FROM AN OBSERVATIONAL STUDY
Background and Aims. Gender-specific medicine in pain management requires considering biological sex and psychosocial factors, as they influence the prevalence, perception, and outcomes of pain treatment. The objective is to analyze the interaction between pain intensity, biopsychosocial impact, and disability. Methods. The observational study was conducted at the Pain Medicine Outpatient Clinic of the Foggia Polyclinic on adult patients suffering from chronic persistent pain. The analysis involved 85 patients (32 males and 53 females). Internationally validated scales were used: NRS, Oswestry Disability Index, and Hamilton. Statistical correlations between these indices, clinical covariates, and administered therapies were assessed, monitoring recurrence rates at 1-, 3-, and 6-month follow-ups. Results. Male patients presented at admission with higher pain intensity (NRS 7.1 vs. 6.5) and functional disability (ODI 63 vs. 40). Females show a higher Hamilton score (11 vs. 8). The temporal analysis clearly shows the different behaviors of the two genders. In males (NRS-ODI: r = 0.730), treatment approaches are delayed ("male stoicism") until the onset of actual disability. In females, functional resilience is greater but influenced by emotional state (Hamilton-ODI: r = 0.461). Males receive more interventional therapies (fix-it approach) than females (conservative medicalization). Conclusions. In males, the interventional approach must be integrated with counseling and functional rehabilitation to prevent relapses. In females, early management of the anxiety-depressive component that underpins disability and reconsidering the use of interventional therapy are priorities.