Search Results (24)

Background: Bladder pain syndrome (BPS) is a chronic, debilitating condition defined by the International Continence Society as bladder-related pelvic pain accompanied by urinary symptoms in the absence of identifiable pathology. Its heterogeneous presentation, unclear pathophysiology, and variable treatment response make management challenging for general urologists. This review aims to provide a practical narrative review of current understanding of BPS, with particular emphasis on diagnosis, phenotyping, and non-operative management strategies relevant to the general urologist. Methods: A narrative literature review was undertaken using PubMed/MEDLINE, Embase, Google Scholar, and major international guideline documents to identify evidence relating to the diagnosis and non-operative management of BPS. Publications from January 2015 to December 2025 were reviewed, with selected landmark earlier studies included, where clinically relevant. Priority was given to guidelines, systematic reviews, randomised trials, and cohort studies. Owing to heterogeneity in study design, patient phenotypes, and reported outcomes, findings were synthesized narratively. Results: BPS represents a heterogeneous spectrum, including Hunner-lesion and non-Hunner phenotypes, with proposed mechanisms involving urothelial dysfunction, chronic inflammation, immune dysregulation, and central sensitisation. Diagnosis remains one of exclusion, relying on careful history, examination, symptom scoring, and selective investigations. Non-operative management is stepwise and multidisciplinary, combining lifestyle modification, pelvic floor therapy, oral agents and intravesical therapy. Available evidence suggests that symptom improvement is often modest but clinically meaningful in selected patients, supporting an individualized, phenotype-informed approach to care with realistic patient counselling. Conclusions: Bladder pain syndrome remains a chronic, multifaceted disorder with profound impact on quality of life, requiring clinicians to approach patients with empathy while recognising the physical, psychological, and social burden of the condition. Effective management requires early recognition, thoughtful phenotyping, exclusion of confusable conditions, and realistic expectation-setting within a multidisciplinary framework. For the general urologist, a structured and compassionate non-operative approach can improve symptom control, support shared decision-making, and help guide timely escalation when required. Full article

Non-specific lipid transfer proteins (nsLTPs) constitute a widely distributed family of plant allergens with substantial clinical relevance, particularly in food allergy. Their marked thermal and proteolytic stability enables them to provoke reactions ranging from mild local symptoms to severe anaphylaxis. This narrative review synthesises current knowledge on nsLTP allergens, focusing on their molecular characteristics, taxonomic distribution, exposure routes, and clinical impact. Major allergenic sources include fruits, nuts and seeds, vegetables and cereals, as well as various pollens. Across these sources, Pru p 3 has emerged as the central and most extensively studied allergen, frequently acting as the primary sensitiser and exhibiting broad cross-reactivity with homologous nsLTPs from diverse plant species. Despite growing evidence, significant knowledge gaps remain regarding sensitisation pathways, environmental modifiers, and phenotype stratification. Continued research is required to improve diagnostic precision and guide the development of targeted therapeutic strategies for patients with nsLTP-mediated allergy. Full article

Background: Persistent pain following orthopaedic trauma is common, often disproportionate to structural healing, and increasingly interpreted as reflecting centrally mediated pain mechanisms. However, the mechanisms, clinical features, diagnostic approaches, prognostic indicators, and management strategies relevant to trauma-related central sensitisation (CS) remain poorly understood. Objective: To map and synthesise existing evidence on CS following orthopaedic trauma, addressing mechanistic pathways, clinical manifestations, epidemiology, assessment methods, management approaches, and health system implications. Methods: A scoping review was conducted in accordance with PRISMA-ScR. Twenty-one studies met the eligibility criteria, comprising nine primary trauma cohorts and 12 contextual mechanistic or review studies relevant to trauma-associated CS. Data were charted across six prespecified domains of mechanistic processes, clinical presentation and diagnostic features, epidemiology and prognosis, assessment tools and outcome measures, interventions, and health system and care delivery considerations. Results: Mechanistic studies demonstrated trauma-induced neuroimmune activation, altered cortical and spinal excitability, and molecular pathways consistent with sensitisation. Clinical studies have identified neuropathic features, widespread pain, and heightened sensory responsiveness following fractures and other injuries. Neurophysiological evidence has indicated early cortical disinhibition following upper limb trauma, whereas epidemiological cohorts have reported persistent pain and disability years after major trauma. Measurement studies have highlighted the limited reliability and specificity of current tools in trauma populations, including quantitative sensory testing and self-report instruments. Early predictors of adverse trajectories include severe acute pain, neuropathic descriptors, psychological distress, and opioid-dominant analgesia. Evidence regarding early intervention, rehabilitation strategies, and system-level screening pathways remains limited. Conclusions: Central sensitisation (CS)–consistent mechanisms after orthopaedic trauma are suggested by convergent mechanistic, neurophysiological, and clinical findings. However, trauma-specific diagnostic criteria, prognostic models, and management frameworks remain underdeveloped. High-quality longitudinal research is needed to clarify early trajectories, refine assessment methods, and establish targeted interventions to reduce long-term pain and disability. Full article

Objectives: Neurodivergent (ND) individuals (e.g., autistic people) are more likely to experience health problems that are characterised by ‘Central Sensitisation’ (CS). Recent research suggests that a so-called ‘Long-COVID’ syndrome might also be explained by a heightened response to internal physiological stimuli, much like in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The primary objective of this study was to establish whether individuals who scored highly on a measure of CS would be more likely to experience long-term symptoms of COVID-19. A secondary aim considered if having a Type D personality was also linked to ongoing COVID-19 symptoms. Method: Using a standardised assessment tool, we examined whether traits associated with autism would predict long-term COVID-19 symptoms in 267 Healthcare Workers (HCWs). We also used a measure of Type D personality to establish if negative affect and social inhibition were related to Long-COVID. Results: A higher number of autistic traits predicted COVID-19 symptoms that lasted more than 12 weeks regardless of formal autism diagnosis. A personality measure also showed that negative affect was associated with experiencing COVID-19 symptoms for 4–12 weeks, though the direction of causality in this case is uncertain. Conclusions: Our main findings were (i) more HCWs scored above threshold for neurodivergence than those who were self-declared as having been diagnosed as neurodivergent; (ii) while there was no association between long-term COVID-19 and self-declared neurodivergent status, scores for the ‘sensory reactivity’ item of a standardised autism scale was predictive of COVID-19 symptoms lasting beyond 12 weeks post-infection; and (iii) HCWs with Type D Personality were not more likely to experience long-term COVID-19. Full article

Objectives: Prolonged opioid use leads to tolerance and hyperalgesia in patients with chronic pain. Apart from an increase in pain, opioid use also leads to several other adverse effects. Nevertheless, the prevalence of opioid use as a treatment for chronic pain remains high, and opioid withdrawal interventions deserve more attention. This study evaluates the effects of a guideline for an opioid withdrawal intervention method that is nested in cognitive behavioral treatment (CBT) and is specifically for patients with a history of long-term opioid use and chronic pain. Methods: We conducted a clinical, exploratory, and mixed-methods study involving pre- and post-measurements on opioid use and health-related quality of life (SF-36), as well as a qualitative analysis of patient experiences (interviews) to evaluate the program. Results: A total of 29 patients were included in the study; 23 of these patients no longer used opioids, and some continued withdrawal under the guidance of their general practitioner. Quality of life improved in all domains, including the amount of pain experienced. No patients reported increased pain levels, and most experienced significantly fewer adverse side effects. Patient satisfaction was high, with no negative long-term side effects of the intervention reported. Conclusions: In light of the results of this study, it is important to address opioid use in patients with chronic pain. There are strong arguments in favor of motivating patients to withdraw from using opioids to treat chronic pain, which can be achieved in combination with CBT. Full article

Background: Osteoarthritis (OA) of the knee is a highly prevalent and heterogeneous condition. Identifying distinct clinical phenotypes within end-stage knee OA populations may inform tailored preoperative management strategies for individuals awaiting total knee replacement (TKR) surgery. Methods: This cross-sectional study employed exploratory factor analysis to identify clinical presentation patterns among patients with knee OA awaiting TKR in South Africa, using modifiable variables including demographic data, physical examination findings, patient-reported outcomes, and functional measures. Results: Three distinct clinical phenotypes emerged: (1) gait and weight—characterised by poor gait mechanics, obesity, and low self-efficacy; (2) central pain—encompassing central sensitisation, depression, and reduced functional performance; and (3) functional factors—reflecting muscular weakness and functional limitations. Conclusions: This study highlights the heterogeneity in clinical presentations among patients with end-stage knee OA awaiting TKR in South Africa. The identified phenotypes suggest a need for tailored, multidisciplinary preoperative interventions incorporating weight management, pain management, psychological support, targeted exercise programs, and behavioural change strategies to optimise post-surgical outcomes and enhance overall care. Full article

Background: Chronic primary orofacial pain (COFP) affects approximately 7% of the population and often leads to reduced quality of life. Patients frequently undergo multiple assessments and treatments across healthcare disciplines, often without a definitive diagnosis. The 2019 ICD-11 classification of chronic primary pain clusters together COFP subtypes based on chronicity and associated functional and emotional impairment. Objective: This study aimed to evaluate whether these subtypes of COFP share common underlying mechanisms by comparing neuroimaging findings. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Searches were performed using Medline (OVID) and Scopus up to April 2025. Inclusion criteria focused on MRI-based neuroimaging studies of participants diagnosed with COFP subtypes. Data extraction included participant demographics, imaging modality, brain regions affected, and pain assessment tools. Quality assessment used a modified Coleman methodological score. Results: Fourteen studies met the inclusion criteria, all utilising MRI and including two COFP subtypes (temporomandibular disorder and burning mouth syndrome). Resting- and task-state imaging revealed overlapping alterations in several brain regions, including the thalamus, somatosensory cortices (S1, S2), cingulate cortex, insula, prefrontal cortex, basal ganglia, medial temporal lobe, and primary motor area. These changes were consistent across both TMD and BMS populations. Conclusions: The findings suggest that chronic primary orofacial pain conditions (TMD and BMS) may share common central neuroplastic changes, supporting the hypothesis of a unified pathophysiological mechanism. This has implications for improving diagnosis and treatment strategies, potentially leading to more targeted and effective care for these patients. Full article

Background: Chronic shoulder pain is a prevalent musculoskeletal disorder often associated with central sensitisation, which limits the effectiveness of conventional therapies. Transcranial direct current stimulation (tDCS) has emerged as a non-invasive neuromodulatory intervention to modulate cortical excitability and potentially improve pain and functional outcomes. Methods: This scoping review followed the Joanna Briggs Institute (JBI) framework and PRISMA-ScR guidelines. A systematic search was conducted across MEDLINE, CENTRAL, Scopus, PEDro, and Web of Science to identify studies evaluating the effects of tDCS on pain and function in adults with rotator cuff disorders, myofascial pain syndrome (MPS), or subacromial pain syndrome (SAPS). Data were extracted and synthesised qualitatively. Results: Four studies met the inclusion criteria. tDCS demonstrated variable efficacy: some trials reported no additional benefit when used alongside corticosteroid injections or sensorimotor training (e.g., SAPS and rotator cuff tendinopathy), while others showed enhanced pain reduction and functional gains, particularly in MPS. Targeting the dorsolateral prefrontal cortex (DLPFC) appeared more effective than stimulating the primary motor cortex (M1) in modulating pain. Functional improvements were generally observed, though not consistently superior to sham interventions. Conclusions: Preliminary evidence suggests that tDCS may represent a promising adjunctive treatment for chronic shoulder pain, particularly in MPS. However, due to the limited number of studies and heterogeneity in methods, conclusions should be interpreted with caution. However, heterogeneity in study protocols, stimulation targets, and patient populations limits conclusive recommendations. Standardised protocols and larger trials are needed to determine the optimal application of tDCS in clinical shoulder pain management. Full article

Background: Low back pain (LBP) is a leading cause of disability worldwide, often driven by distinct pain mechanisms: nociceptive, neuropathic, and central sensitization. Accurate classification of these mechanisms is critical for guiding effective, targeted treatments. Methods: A scoping review was conducted following the Joanna Briggs Institute methodology and reported according to PRISMA-ScR guidelines. A comprehensive literature search was performed in MEDLINE, Cochrane CENTRAL, Scopus, PEDro, and Web of Science. Eligible studies included adults with LBP and focused on clinical criteria for classifying pain mechanisms. Data on study methods, population characteristics, and outcomes were extracted and synthesized. Results: Nine studies met the inclusion criteria. Nociceptive pain was characterized by localized symptoms proportional to mechanical triggers, with no neurological signs. Neuropathic pain was associated with burning sensations, dysaesthesia, and a positive neurodynamic straight leg raise (SLR) test. Central sensitization featured widespread pain, hyperalgesia, and disproportionate symptoms. Tools such as painDETECT, DN4, and the Central Sensitisation Inventory (CSI) were validated for neuropathic and central sensitization pain. Central sensitization and neuropathic pain were linked to greater disability and psychological distress compared to nociceptive pain. Conclusions: This review aims to provide a historical perspective on pain mechanism classifications and to explore how previous frameworks have influenced current diagnostic concepts in physiotherapy practice. By synthesizing key clinical criteria used to differentiate between nociceptive, neuropathic, and central sensitization pain, this review proposes a practical framework to improve the accuracy of pain classification in clinical settings. Full article

For patients with chronic pain and persistent physical symptoms, understanding the mechanism of central sensitisation may help in understanding how symptoms persist. This cross-sectional study investigated the association of central sensitisation with depression, anxiety, and somatic symptoms. Four hundred and fifteen adults attending an outpatient psychosomatic clinic were evaluated. Participants completed the Hospital Anxiety and Depression Scale, Somatic Symptom Scale 8, and the Central Sensitisation Inventory. The relationships between these factors were examined using descriptive statistics and multiple logistic regression analyses. The mean age was 42.3 years, and 59% were female. The disorders included adjustment disorders (n = 70), anxiety disorders (n = 63), depressive disorders (n = 103), feeding and eating disorders (n = 30), sleep–wake disorders (n = 37), somatic symptoms and related disorders (n = 84), and others (n = 28). In multiple logistic regression analyses, higher central sensitisation was associated with more severe anxiety, depression, and somatic symptoms after controlling for potential confounders. In the disease-specific analysis, somatic symptoms correlated more positively with central sensitisation than with depression or anxiety. Central sensitisation and depression, anxiety, and somatic symptoms were associated with patients attending an outpatient clinic. These findings highlight the importance of evaluating depression, anxiety, and somatic symptoms when assessing central sensitisation. Full article

Central sensitisation is defined as a multifactorial etiopathogenetic condition involving an increase in the reactivity of nociceptive neurons and alterations in pain transmission and perception in the central nervous system. Patients may present with widespread chronic pain, fatigue, sleep disturbance, dizziness, psychological (e.g., depression, anxiety, and anger) and social impairment. Pain can be spontaneous in onset and persistence, characterised by an exaggerated response and spread beyond the site of origin, and sometimes triggered by a non-painful stimulus. Whole-body cryostimulation (WBC) could be an adjuvant therapy in the management of this type of pain because of its global anti-inflammatory effect, changes in cytokines and hormone secretion, reduction in nerve conduction velocity, autonomic modulation, and release of neurotransmitters involved in the pain pathway. In several conditions (e.g., fibromyalgia, rheumatoid arthritis, and chronic musculoskeletal pain), WBC affects physical performance, pain perception, and psychological aspects. Given its multiple targets and effects at different organs and levels, WBC appears to be a versatile adjuvant treatment for a wide range of conditions of rehabilitation interest. Further research is needed to fully understand the mechanisms of analgesic effect and potential actions on pain pathways, as well as to study long-term effects and potential uses in other chronic pain conditions. Full article

The prevalence of neurological conditions which manifest with chronic pain is increasing globally, where the World Health Organisation has now classified chronic pain as a risk factor for death by suicide. While many chronic pain conditions have a definitive underlying aetiology, non-somatic conditions represent difficult-to-diagnose and difficult-to-treat public health issues. The interaction of the immune system and nervous system has become an important area in understanding the occurrence of neuroinflammation, nociception, peripheral and central sensitisation seen in chronic pain. More recently, however, the role of the resident microbial species in the human gastrointestinal tract has become evident. Dysbiosis, an alteration in the microbial species present in favour of non-beneficial and pathogenic species has emerged as important in many chronic pain conditions, including functional somatic syndromes, autoimmune disease and neurological diseases. In particular, a decreased abundance of small chain fatty acid, e.g., butyrate-producing bacteria, including Faecalibacterium, Firmicutes and some Bacteroides spp., is frequently evident in morbidities associated with long-term pain. Microbes involved in the production of neurotransmitters serotonin, GABA, glutamate and dopamine, which mediate the gut-brain, axis are also important. This review outlines the dysbiosis present in many disease states manifesting with chronic pain, where an overlap in morbidities is also frequently present in patients. Full article

The dorsal horn (DH) neurons of the spinal cord play a critical role in nociceptive input integration and processing in the central nervous system. Engaged neuronal classes and cell-specific excitability shape nociceptive computation within the DH. The DH hyperexcitability (central sensitisation) has been considered a fundamental mechanism in mediating nociceptive hypersensitivity, with the proven role of Ca²⁺-permeable AMPA receptors (AMPARs). However, whether and how the DH hyperexcitability relates to changes in action potential (AP) parameters in DH neurons and if Ca²⁺-permeable AMPARs contribute to these changes remain unknown. We examined the cell-class heterogeneity of APs generated by DH neurons in inflammatory pain conditions to address these. Inflammatory-induced peripheral hypersensitivity increased DH neuronal excitability. We found changes in the AP threshold and amplitude but not kinetics (spike waveform) in DH neurons generating sustained or initial bursts of firing patterns. In contrast, there were no changes in AP parameters in the DH neurons displaying a single spike firing pattern. Genetic knockdown of the molecular mechanism responsible for the upregulation of Ca²⁺-permeable AMPARs allowed the recovery of cell-specific AP changes in peripheral inflammation. Selective inhibition of Ca²⁺-permeable AMPARs in the spinal cord alleviated nociceptive hypersensitivity, both thermal and mechanical modalities, in animals with peripheral inflammation. Thus, Ca²⁺-permeable AMPARs contribute to shaping APs in DH neurons and nociceptive hypersensitivity. This may represent a neuropathological mechanism in the DH circuits, leading to aberrant signal transfer to other nociceptive pathways. Full article

The primary role of Notch is to specify cellular identities, whereby the cells respond to amazingly small changes in Notch signalling activity. Hence, dosage of Notch components is crucial to regulation. Central to Notch signal transduction are CSL proteins: together with respective cofactors, they mediate the activation or the silencing of Notch target genes. CSL proteins are extremely similar amongst species regarding sequence and structure. We noticed that the fly homologue suppressor of hairless (Su(H)) is stabilised in transcription complexes. Using specific transgenic fly lines and HeLa RBPJ^KO cells we provide evidence that Su(H) is subjected to proteasomal degradation with a half-life of about two hours if not protected by binding to co-repressor hairless or co-activator Notch. Moreover, Su(H) stability is controlled by MAPK-dependent phosphorylation, matching earlier data for RBPJ in human cells. The homologous murine and human RBPJ proteins, however, are largely resistant to degradation in our system. Mutating presumptive protein contact sites, however, sensitised RBPJ for proteolysis. Overall, our data highlight the similarities in the regulation of CSL protein stability across species and imply that turnover of CSL proteins may be a conserved means of regulating Notch signalling output directly at the level of transcription. Full article

The presence of pain sensitisation has been documented and reported as being a possible cause of treatment failure and pain chronicity in several musculoskeletal conditions, such as tendinopathies. The aim of the present study is to analyse existing evidence on pain sensitisation in tendinopathies comparing the local and distant pain thresholds of healthy and affected subjects with distinct analysis for different tendinopathies. PubMed, Cochrane Central Register, Scopus, and Web Of Science were systematically searched after registration on PROSPERO (CRD42020164124). Level I to level IV studies evaluating the presence of pain sensitisation in patients with symptomatic tendinopathies, documented through a validated method, were included. A meta-analysis was performed to compare local, contralateral, and distant pain thresholds between patients and healthy controls with sub-analyses for different tendinopathies. Meta-regressions were conducted to evaluate the influence of age, activity level, and duration of symptoms on results. Thirty-four studies out of 2868 were included. The overall meta-analysis of local pressure pain thresholds (PPT) documented an increased sensitivity in affected subjects (p < 0.001). The analyses on contralateral PPTs (p < 0.001) and distant PPTs (p = 0.009) documented increased sensitivity in the affected group. The results of the sub-analyses on different tendinopathies were conflicting, except for those on lateral epicondylalgia. Patients’ activity level (p = 0.02) and age (p = 0.05) significantly influenced local PPT results. Tendinopathies are characterized by pain sensitisation, but, while features of both central and peripheral sensitisation can be constantly detected in lateral epicondylalgia, results on other tendinopathies were more conflicting. Patients’ characteristics are possible confounders that should be taken into account when addressing pain sensitisation. Full article