Search Results (235)

Background: Congenital Insensitivity to Pain and Anhidrosis (CIPA) is a rare autosomal recessive disorder characterized by congenital analgesia, anhidrosis, and multisystem involvement affecting the musculoskeletal, cutaneous, oral, and para-oral structures. This case report describes the oral phenotype and multidisciplinary clinical management of a child with CIPA. Case Description: A 9-year-old boy presented with poor oral hygiene, multiple severely damaged teeth, masticatory difficulty, limited mouth opening, impaired bolus control, and para-oral traumatic injuries. Medical and orthopedic history indicated recurrent painless fractures, self-inflicted injuries, cutaneous scarring, and recurrent hyperpyrexia. Oral self-injury associated with CIPA was suspected and supported by the Nociception Assessment Test and Minor’s Iodine–Starch Test. Although the clinical findings were suggestive of CIPA, the diagnosis remained presumptive due to the absence of confirmatory molecular or histopathological testing. Management: A wearable wireless continuous temperature-monitoring device was prescribed to assist in tracking hyperpyrexia associated with CIPA (RHA-CIPA). A conservative, staged, multidisciplinary treatment was planned rather than full-mouth extraction, emphasizing prevention of dental sepsis and mitigation of future self-injury. Dental procedures were performed under local anesthesia to manage discomfort related to tactile hyperesthesia. To reduce nocturnal biting and oral trauma, a hard acrylic occlusal protector was fabricated using an intraoral scanner and a 3D-printed cast. The patient was followed for 12 months. Outcomes: At the 12-month follow-up, clinical improvement was observed, with particularly notable gains in cheek elasticity and soft tissue resilience. Conclusions: This case highlights the considerable challenges involved in the interdisciplinary management of children with CIPA, including oral self-injury prevention, limited mouth opening, and the necessity of close coordination with medical specialties. These findings are descriptive observations of a single case and do not establish efficacy or generalizability of any intervention. Full article

Transient receptor potential vanilloid 1 (TRPV1) channels are critical mediators of cutaneous allergic inflammation, contributing to pruritus, erythema, and hypersensitivity in allergic skin disorders. Despite their therapeutic potential, clinically available TRPV1 inhibitors remain limited, leaving effective treatment options lacking. Here, we focused on a self-constructed virtual pentapeptide library and identified a highly selective TRPV1 inhibitor that demonstrated pronounced anti-allergic effects in human skin assays. Through structure-based virtual screening of approximately 200,000 peptide conformations, five candidate pentapeptides, especially P5 (DQKNC), exhibited the inhibition. Electrophysiological recordings showed that P5 inhibited TRPV1 currents with nanomolar potency, while exhibiting negligible effects on major cardiac and neuronal ion channels, highlighting its favorable selectivity and safety profile. In capsaicin-induced human skin hypersensitivity tests, topical P5 significantly reduced burning pain, erythema, and pruritus, with simultaneous application providing the most robust relief. These findings reveal a short peptide with strong TRPV1 selectivity and demonstrable efficacy in alleviating skin inflammation and allergic responses, supporting the notion that rationally designed pentapeptides may represent promising topical therapeutics for allergic skin disorders. Full article

Background/Objective: The purpose of this study was to determine whether the effects of pain education combined with physiotherapy could be explained by changes in psychological well-being and self-efficacy in individuals with chronic low back pain (LBP). Methods: This study includes a secondary analysis (mediation analysis) of a randomized controlled trial (RCT) that compares the effect of physiotherapy and pain education with physiotherapy alone. The Roland-Morris Disability Questionnaire, assessed at six weeks, was used as a primary outcome in this study, with pain intensity as a secondary outcome. The World Health Organization Five Well-Being Index (WHO-5) and the General Self-Efficacy Scale were evaluated as potential mediators. Causal mediation analysis based on a counterfactual framework was employed to estimate both direct and indirect effects. Results: The analyses comprised 46 participants (mean age = 42.2 years; 54.3% female) who received pain education along with physiotherapy. In the mediation models, improvements in emotional well-being (assessed by WHO-5) explained approximately one quarter of the effect of the intervention on disability (average causal mediation effect = −1.66, 95% CI [−2.8, −0.72], p < 0.001). By contrast, self-efficacy did not significantly mediate disability, and neither factor accounted for changes in pain intensity. Sensitivity analyses suggested that the indirect effect on psychological well-being was reasonably robust against potential unmeasured confounding factors. Conclusions: Enhancements in psychological well-being were associated with reductions in disability following pain education, whereas self-efficacy did not emerge as a significant mediator. These findings may support the value of incorporating mental well-being strategies within rehabilitation programs for chronic LBP. Full article

Background: Knee osteoarthritis (OA) is a leading cause of disability globally. Conventional physiotherapy, while effective, faces barriers including accessibility and adherence. Telerehabilitation augmented by wearable sensor technology and AI-driven feedback offers a scalable alternative. Objective: This pilot randomized controlled trial compared the feasibility, safety, and preliminary clinical effectiveness of a sensor-based telerehabilitation protocol using the KneE-PAD patient monitoring approach which was also combined with an avatar-guided visual feedback add-on tool. Although this approach is capable of AI-driven postural error detection, this feature was not enabled during the current study, and feedback was provided solely through visual cues. Methods: Twenty adults with radiographically confirmed Kellgren–Lawrence grade 1 to 3 knee OA were randomized into two groups (Control/Intervention groups, n = 10 in each). The control group received in-person physiotherapy, while the intervention group engaged in remote rehabilitation supported by wearable sEMG and IMU sensors. The 8-week program included supervised and home-based sessions. Primary outcomes were WOMAC scores (Functionality/Pain), quadriceps strength, and sEMG-derived neuromuscular activation. Secondary outcomes included Timed Up and Go test (TUG), psychological measures (HADS, TSK), and self-efficacy measure (ASES). Analyses employed both parametric and non-parametric statistics including an effect size estimation. Results: Both groups demonstrated significant improvements in WOMAC total scores (Intervention: −11.8 points; Control: −6.4 points), exceeding the minimal clinically important difference (MCID) for knee OA. Strength and mobility also improved significantly in both groups, with the Intervention group showing superior gains in sEMG measures (RMS: p = 0.0077; Peak-to-Peak: p < 0.005), indicating enhanced neuromuscular adaptation. TUG performance improved more in the intervention group (–3.17 s vs. –2.57 s, p = 0.037). Psychological outcomes favored the control group, particularly in depression scores (HADS-D, t(18) = 2.37, p = 0.03). Adherence was high (94.8%), with zero attrition and no adverse events. Conclusions: The KneE-PAD monitoring approach offers a feasible and clinically effective alternative to conventional physiotherapy, enhancing neuromuscular outcomes through real-time sensor feedback. These findings support the viability of intelligent telerehabilitation for scalable OA care and inform the design of future large-scale trials. Full article

Recovery in osteoarthritis (OA) is a multidimensional construct that extends beyond symptom reduction to encompass how individuals make sense of, adapt to, and live with their condition. Patient expectations appear to play a central role in shaping this process, influencing how individuals define recovery, cope with functional limitations, and evaluate treatment outcomes. Understanding these expectations is essential for improving satisfaction and functional progress in OA management. This scoping review synthesized evidence on patient expectations in knee, hip and generalized OA and examined how these expectations influence treatment outcome and satisfaction. A PRISMA-ScR–informed scoping review was conducted across PubMed, Embase, CINAHL, PsycINFO, and Web of Science up to September 2025. Eligible studies included adults with OA reporting on treatment expectations, expectation fulfillment, or expectations about their ability to cope (self-efficacy). Both qualitative and quantitative designs were included. Data were extracted and organized for study characteristics, population, expectation domains, and outcomes. Sixteen studies met the inclusion criteria, encompassing qualitative syntheses, cohort studies and systematic reviews. Across study designs, higher or fulfilled expectations were consistently associated with greater satisfaction, pain reduction, and functional improvement. Unrealistic or unfulfilled expectations predicted poorer clinical outcomes and dissatisfaction. Expectations surrounding treatment and clinical outcomes may plausibly influence recovery by shaping physiological responses, emotional reactions and patient engagement with rehabilitation. These findings highlight the importance of aligning clinical interventions with patient expectations. Integrating expectation assessment and recalibration into OA care may enhance adherence and patient satisfaction. Future research should further explore expectations as modifiable therapeutic targets and examine how they interact with factors such as symptom duration, severity and pain extension. Such combinations may clarify which patient profiles are most responsive to expectation-focused interventions. Overall, expectations emerge as a central component of recovery and a promising avenue for more person-centered physiotherapy and rehabilitation practice. Full article

Vulvodynia is a chronic vulvar pain condition that can interfere with women’s developmental processes and overall well-being. Adopting a broader perspective of women’s health informed by lifespan developmental and biopsychosocial frameworks, this study examined psychosocial factors related to the psychological well-being of Italian women with vulvodynia. Between December 2023 and December 2024, a total of 533 women diagnosed with vulvodynia completed an online survey. The survey included questions about sociodemographics and the illness, as well as validated measures of dyadic adjustment, social support, self-efficacy, perceived stress, and psychological well-being. Descriptive statistics, group comparisons, Pearson correlations, and hierarchical multiple regressions were performed. Nearly two-thirds of the women reported symptoms lasting over five years, and 44% experienced severe pain. Those with more intense pain, longer symptom duration, or delayed diagnosis reported lower well-being and higher stress. Satisfaction with treatment was linked to greater well-being. Psychological well-being was strongly correlated with social support, dyadic adjustment, and psychological resources. Regression analyses identified younger age, higher pain intensity, lower treatment satisfaction, reduced social support, lower self-efficacy, and greater stress as predictors of poorer psychological well-being. Vulvodynia should be considered a psychosocial and developmental challenge as well as a medical condition. These findings underscore the importance of viewing vulvodynia as not only a medical condition, but also a psychosocial and developmental challenge within women’s broader health trajectories, highlighting the need for interventions that address pain and provide structured emotional support to strengthen psychological and relational resources. Full article

Background: Knee osteoarthritis (OA) is a prevalent musculoskeletal condition associated with pain, functional limitation, and reduced quality of life. Telerehabilitation has emerged as a scalable intervention, yet many platforms lack neuromuscular feedback or objective-monitoring capabilities. The KneE-PAD system uniquely integrates electromyographic and inertial sensing to provide personalized feedback and remote performance tracking. Objective: To evaluate the clinical effectiveness of a sensor-augmented telerehabilitation system (KneE-PAD) compared to conventional face-to-face physiotherapy in older adults with mild-to-moderate knee OA. Methods: In this single-blind randomized controlled trial, 42 older adults (mean age 68.4 ± 5.7 years) were randomly assigned to either KneE-PAD telerehabilitation or conventional physiotherapy for eight weeks. KneE-PAD sessions incorporated real-time electromyographic and motion feedback, while physiotherapists remotely supervised training. Assessments were performed at baseline, post-intervention, and 12-week follow-up. Primary outcomes included quadriceps strength, neuromuscular activation, and WOMAC scores. Secondary outcomes covered functional mobility, psychological distress, self-efficacy, and fear of movement. Results: The telerehabilitation group demonstrated notable improvements in neuromuscular activation, quadriceps strength, and functional capacity, all exceeding clinically meaningful thresholds. Functional mobility and pain outcomes showed substantial gains compared with the control group, while psychological indicators (self-efficacy and depressive symptoms) exhibited modest but positive trends. Between-group comparisons consistently favored KneE-PAD, with effects maintained at the 12-week follow-up, confirming both clinical and functional robustness. Conclusions: Sensor-augmented telerehabilitation using the KneE-PAD platform appears to be a feasible and potentially effective alternative to conventional physiotherapy for knee OA. By combining real-time feedback, motor learning reinforcement, and remote monitoring, the system may enhance neuromuscular and functional recovery. These findings should be confirmed in larger and longer-term trials. Trial Registration: ClinicalTrials.gov: NCT06416332. Full article

Background: This study, designed by the Greek Research Alliance for the Study of Headache and Pain (GRASP), sought to prospectively examine whether the treatment with two consecutive OnabotulinumtoxinA (BoNTA) cycles might improve the frequency and severity of chronic migraine (CM) with comorbid bruxism. We also explored whether the potential BoNTA-related alleviation of bruxism can directly influence the improvements in migraine efficacy outcomes. Methods: A total of 58 CM patients with comorbid bruxism at baseline, attaining two consecutive (quarterly given) BoNTA cycles, were studied. The changes in bruxism-related pain were assessed with the 0–10 numeric scale PI-NRS. Bruxism was clinically diagnosed using the self-report Bruxscreen-Q questionnaire. Any phenotypic changes in bruxism, according to Bruxscreen-Q, from baseline (T0) to the last efficacy evaluation follow-up (T1), were analyzed and then compared. Migraine-related efficacy and disability outcomes, mostly mean headache days (MHD), were also compared between T0 and T1. Results: BoNTA exerted significant improvements in bruxism-related pain, with PI-NRS median scores being significantly reduced from 7 at T0 to 3 at T1 (p < 0.001). The rates of masseter hypertrophy at T1 significantly dropped, compared to T0 (chi-square: 16; p < 0.001). Patients also self-reported significant improvements in the Bruxscreen-Q items at T1, compared to T0. At T1, 41/58 (70.7%) patients responded to BoNTA. The significant decrease in MHD frequency at T1 was positively correlated with improvements in bruxism-related pain severity (Pearson’s correlation: 0.710; p < 0.001). Conclusions: BoNTA exerts dual beneficial effects towards both the reduction of migraine frequency and the alleviation of bruxism-related pain and disability. Both of these effects seem closely interrelated in our study. Full article

This review focuses on hydrogel-based systems specifically designed for non-opioid analgesics, aiming to improve efficacy, safety, and translational applicability. The opioid crisis has intensified the need for safer and more effective alternatives in pain management. Non-opioid analgesics including NSAIDs, acetaminophen, gabapentinoids, antidepressants, anticonvulsants, NMDA receptor antagonists, topical agents, and cannabinoids offer promising options but are limited by rapid clearance, short half-lives, and off-target effects. Hydrogel-based drug delivery systems present a novel solution by enabling controlled, localized, and sustained release of analgesics, thus improving therapeutic efficacy and minimizing systemic toxicity. Advances in stimulus-responsive, self-healing, mechanically robust, and hybrid or nanocomposite hydrogels have broadened their biomedical applications and clinical relevance. This narrative review summarizes key hydrogel technologies and their integration with non-opioid analgesic agents. We explore encapsulation strategies, drug release mechanisms, and emerging clinical data, while also addressing critical challenges such as biocompatibility, mechanical durability, and translational scalability. Interdisciplinary collaboration between material scientists, clinicians, and regulatory experts is essential to advance hydrogel-based therapies from bench to bedside. Overall, hydrogel platforms hold transformative potential in optimizing non-opioid analgesic delivery and redefining the future of pain management. Full article

Background and Clinical Significance: Hell’s Itch is a rare, intensely uncomfortable post-sunburn condition with burning pruritus emerging 24–72 h after UV exposure. This condition often goes unrecognized and is frequently misdiagnosed by healthcare providers due to a lack of knowledge and familiarity. Standard antipruritic measures are often ineffective, and patients frequently rely on anecdotal self-management. Case Presentation: Three healthy adult males between 23 and 28 years old experienced multiple episodes of delayed-onset intense pruritus following moderate-to-severe sun exposure. The patients experienced a burning or stinging pain which they described as “fire ants” or “thumbtacks,“ and their symptoms started between 24 and 72 h after sun exposure without any rash or fever symptoms. The patients did not achieve symptom relief from standard treatments which included oral antihistamines and topical lidocaine, NSAIDs, aloe vera, and cold compresses. The patients received β-alanine treatment through pre-workout supplements or pure powder after consulting non-clinical sources. Each patient ingested β-alanine and reported rapid relief (itch 8–10/10 → 1–2/10) lasting 2–3 h. The only adverse effect reported by one patient was mild paresthesia. Conclusions: This case introduces β-alanine as a potential off-label therapy for Hell’s Itch and emphasizes the psychological burden and clinical complexity of the condition. While anecdotal, further study is needed to elucidate the mechanism of action of β-alanine in relieving symptoms of Hell’s Itch, as well as assess safety and efficacy in controlled settings. Increased clinical awareness of Hell’s Itch may reduce patient distress and improve management strategies. Full article

Background/Objectives: Chronic musculoskeletal pain (CMSKP) affects up to 40% of adolescents and leads to substantial disability, reduced quality of life, and long-term health risks. Physical activity is central to treatment, but adherence to moderate-to-vigorous physical activity (MVPA) is inconsistent. We evaluated higher-resilience constructs—self-efficacy, pain acceptance, motivational stage, and affect—and hypothesized that higher resilience would be associated with greater objectively measured physical activity, better daily functioning, and higher quality of life in adolescents with CMSKP. Methods: Forty-three adolescents (13–18 years) with CMSKP completed measures of physical activity-specific self-efficacy, acceptance (AFQ-Y), motivational stage (PSOCQ-A), and affect (PANAS-C). Participants wore activPAL monitors to assess MVPA, light activity, and sedentary time. Physical function endurance was measured by the six-minute walk test (6MWT) and the Functional Disability Inventory (FDI); quality of life by the Pediatric Quality of Life Inventory (PedsQL). Spearman’s correlations assessed associations among resilience variables, physical activity metrics, 6MWT distance, FDI, and PedsQL. Results: MVPA was correlated positively with 6MWT distance (ρ = 0.48, p = 0.002) and negatively with FDI scores (ρ = −0.56, p < 0.001). Self-efficacy related to higher MVPA (ρ = 0.41, p = 0.009), better endurance (ρ = 0.36, p = 0.017), and lower disability (ρ = −0.38, p = 0.013). Acceptance was correlated with PedsQL total (ρ = 0.45, p = 0.004); motivation (specifically maintenance) scores were correlated with higher quality of life (ρ = 0.33, p = 0.027). Light activity and sedentary time were not significantly linked to functional or psychosocial outcomes. In a step-wise regression, only physical activity self-efficacy for ambulation at school predicted MVPA, B = 1.56, p = 0.008. Conclusions: Resilience constructs—including self-efficacy, acceptance, and readiness to change—were meaningfully associated with MVPA, daily functioning, and quality of life, and may have implications for treatment development. Full article

Background/Objectives: Patients in palliative care often experience multifaceted forms of suffering that extend beyond physical symptoms, including existential distress, loss of meaning, and emotional pain. Ketamine-assisted psychotherapy (KAP) has emerged as a promising intervention for alleviating such complex forms of suffering, yet models specifically tailored to palliative populations remain scarce. This narrative review synthesizes current evidence on ketamine’s neurobiological, psychological, and experiential effects relevant to end-of-life care, and presents a novel, time-limited KAP model designed for use in palliative settings. Methods: Drawing from both biochemical and psychedelic paradigms, the review integrates findings from neuroscience, phenomenology, and clinical practice. In particular, it incorporates a dual-level experiential framework informed by recent models distinguishing ketamine’s differential effects on self-processing networks: the Salience Network (SN), related to embodied self-awareness, and the Default Mode Network (DMN), associated with narrative self-construction. This neurophenomenological perspective underpins the rationale for using two distinct dosing sessions. Results: The article proposes a short-course, time-limited KAP model that integrates preparatory and integrative psychotherapy, two ketamine dosing sessions (one low-dose and one moderate-dose), concurrent psychotherapy, goals of care discussion (GOCD), and optional pharmacological optimization. The model emphasizes psychological safety, meaning-making, and patient-centered care. The sequential dosing strategy leverages ketamine’s unique pharmacology and experiential profile to address both bodily and narrative dimensions of end-of-life distress. Conclusions: This dissociative-psychedelic model offers a compassionate, pragmatic, and theoretically grounded approach to relieving psychological and existential suffering in palliative care. By integrating neurobiological insights with psychotherapeutic processes, it provides a flexible and patient-centered framework for enhancing meaning, emotional resolution, and quality of life at the end of life. Further research is needed to evaluate its clinical feasibility, safety, and therapeutic efficacy. Full article

Introduction: Botulinum toxin-A (BTX-A) injections are regularly used to treat temporomandibular disorders (TMD). However, consensus regarding the long-term efficacy of BTX-A for TMD-related myalgia remains lacking. This pragmatic, practice-based clinical study aimed to evaluate the Patient-Reported Outcome Measures of pain, health status, quality of life, and function after BTX-A injections in patients with TMD-related myalgia. Methods: This prospective cohort study included 35 patients with TMD-related myalgia who received BTX-A injections in the masseter and temporalis muscles. The Visual Analogue Scale for pain, the EQ-5D-3L for health status, the Oral Health Impact Profile-14 for oral health-related quality of life, the Mandibular Function Impairment Questionnaire for function and the maximum interincisal opening were assessed before treatment and at one, three and six months follow-up. Results: Patients reported a statistically significant and clinically relevant reduction in pain (p < 0.001), improvement of health status (p ≤ 0.003), and oral health-related quality of life (p < 0.001) at one-month follow-up, which remained present at three and six months post-treatment. Self-reported mandibular function and active and passive mouth opening showed no significant change over all time points. Conclusions: In this pragmatic cohort, BTX-A injections in the masseter and temporalis muscles seem to improve pain and oral health-related quality of life in patients with TMD-related myalgia within one month and show effects lasting up to six months, while mandibular function did not improve. Full article

Objectives: Multidisciplinary management of chronic pain benefits many patients, although some continue to experience refractory pain. Administration of lidocaine infusions (LI) to manage certain chronic pain conditions has been reported in adults, but evidence is limited for its utility in managing pediatric chronic pain. We reviewed LIs for refractory pain in children to (1) describe the patient population that received LI and (2) evaluate the response to LI. Methods: With IRB approval, a retrospective review of patients receiving LI for refractory pain between 2016 and 2021 was conducted at Boston Children’s Hospital. Demographic, medical, pain, sleep, and school function information was collected through self-report and from the electronic medical record. Longitudinal outcomes for a subset of these patients were analyzed using the Chronic Pain Repository database. Results: During the study period, 3959 patients presented for management of chronic pain. Among this population, 184 (5%) patients aged 22 years or younger ultimately received LI as part of their pain management. A total of 350 LIs were administered and were well tolerated. During approximately 42% of the infusions, patients experienced an immediate statistically significant decrease in pain scores. Among the patients with follow-up data, pain improvement was not sustained. Discussion: LI for the treatment of chronic pain appears safe and may be useful for managing refractory pain in pediatrics. Although approximately half of the patients who received LI reported an immediate positive response, the small follow-up sample did not show a continued response. Study limitations preclude demonstrating long-term efficacy of LI; therefore, a prospective study is critical. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is associated with impaired functional capacity, persistent fatigue, and poor health-related quality of life despite advances in pharmacological therapy. Exercise training has been proposed as a non-pharmacological intervention, but its efficacy and safety remain incompletely defined. This systematic review aimed to evaluate the effects of exercise training on functional aerobic capacity and quality of life in adults with SLE. Methods: A comprehensive search of PubMed, EMBASE, Cochrane Library, and PEDro was conducted to identify randomized controlled trials published up to October 2022, in accordance with the PRISMA guidelines. Results: Twelve randomized controlled trials involving 619 participants were included. Exercise interventions were heterogeneous and comprised aerobics, resistance, combined programs, vibration training, home-based protocols, and counseling strategies, with durations ranging from 6 weeks to 12 months. Supervised aerobic and combined interventions consistently improved functional aerobic capacity, while quality of life benefits were reported across several domains, particularly physical health, vitality, and fatigue. Additional positive effects were observed on fatigue, depression, pain, sleep, insulin sensitivity, and self-care ability, without evidence of increased disease activity. Conclusions: Structured exercise is safe and can meaningfully enhance functional capacity and quality of life in patients with SLE, supporting its incorporation into multidisciplinary clinical management. Full article