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ABSTRACT Background Objectives Methods Results Conclusion Temporomandibular disorders (TMDs) are conditions that involve the temporomandibular joints, masticatory muscles, and associated tissues, causing orofacial pain. Central sensitisation (CS) is a relevant part of the TMD pathophysiology. Migraine, psychological aspects, parafunctional oral habits and widespread pain are commonly associated with both TMD and CS and could confound the association between them.To investigate the association between painful TMD and the Central Sensitisation Inventory (CSI) score, and to assess the presence of confounders in this association.Cross‐sectional study that assessed women with and without orofacial pain complaints using telehealth. The TMD Pain Screener and an online physical examination determined the presence of painful TMD. The following questionnaires were applied: CSI, Headache Screening Questionnaire, Generalized Anxiety Disorder‐7, Patient Health Questionnaire‐9, Oral Behavior Checklist, Jaw Functional Limitation Scale and the Nordic musculoskeletal questionnaire. A single regression investigated the association between the CSI score and TMD, and a multiple regression investigated the effect of the other outcomes as possible confounders. Confounding was considered present when the association between TMD and the CSI score changed more than 10% after adding a possible confounder to the regression model.Forty‐two women with painful TMD and 53 without TMD were included. There was a significant association between the CSI score and the presence of painful TMD (R2 = 0.639; p < 0.001). This association changed when the following outcomes were added to the model: presence of migraine, symptoms of depression, widespread pain and parafunctional oral habits.The positive association between TMD and the CSI score was confounded by migraine, symptoms of depression, widespread pain and parafunctional oral habits. [ABSTRACT FROM AUTHOR]

Abstract Background Pain, the primary complaint in rheumatoid arthritis (RA), is multifaceted, and may be driven by inflammatory disease activity and central sensitisation. We aimed to ascertain what proportion of RA pain severity is explained by markers of inflammation and quantitative sensory testing (QST) indices of central sensitisation. Methods This was a cross-sectional analysis of data from individuals with clinically active RA. Pain severity was assessed using numerical rating scales and inflammation via 28-joint Disease Activity Score (DAS28) and Ultrasound (Greyscale, Power Doppler). Pain sensitivity was assessed by ‘static’ (tibialis anterior or brachioradialis pressure pain detection threshold-PPT-TA/PPT-BR) and ‘dynamic’ (temporal summation-TS, conditioned pain modulation-CPM) QST. Bivariate associations used Spearman’s correlation coefficients, and multivariable linear regression models determined relative contributions to pain severity. Results In bivariate analyses of N = 96 (age 65 ± 10y, 77% females) people with RA, pain severity was significantly associated with inflammation indices (r = 0.20 to 0.55), and CPM (r=-0.26). In multivariable models that included TS, CPM, age, sex, and body mass index, inflammation indices remained significantly associated with pain severity. Multivariable models explained 22 to 27% of pain variance. Heterogeneity was apparent for associations with pain between subscores for pain now, strongest or average over the past 4-weeks. Conclusions In individuals with clinically active RA, markers of inflammatory disease activity best explain RA pain with only marginal contributions from QST indices of central sensitisation. Although inflammation plays a key role in the experience of RA pain, the greater proportion of pain severity remains unexplained by DAS28 and ultrasound indices of inflammation.

In the cancer pain setting, ketamine has been typically employed as a co-analgesic for opioid refractory and neuropathic pain. One controversial topic is whether subanesthetic ketamine be considered when managing opioid refractory cancer pain. In this "Controversies in Palliative Care" article, three clinicians independently answer this question. Specifically, each clinician provides a synopsis of the key studies that inform their thought processes, share practical advice on their clinical approach, and highlight the opportunities for future research. Three independent clinicians reported a divergence of opinion regarding the usefulness of subanesthetic ketamine for managing opioid refractory cancer pain. All investigators acknowledged the lack of high-quality trials. All agreed on the need for adequately powered trials, the development of standardized methodology, and the exploration of any patient sub-populations that may benefit from ketamine for cancer related pain. [ABSTRACT FROM AUTHOR]

• EEG research in Fibromyalgia, Chronic Fatigue Syndrome (ME/CFS) and Long COVID helps understand their dominant symptoms. • Fibromyalgia Syndrome and ME/CFS present differing EEG brainwave activity patterns. • EEG research in Long COVID shows mixed results so far and needs further investigations taking account of Long COVID phenotypes. Fibromyalgia Syndrome (FMS), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC) are similar multisymptom clinical syndromes but with difference in dominant symptoms in each individual. There is existing and emerging literature on possible functional alterations of the central nervous system in these conditions. This review aims to synthesise and appraise the literature on resting-state quantitative EEG (qEEG) in FMS, ME/CFS and LC, drawing on previous research on FMS and ME/CFS to help understand neuropathophysiology of the new condition LC. A systematic search of MEDLINE, Embase, CINHAL, PsycINFO and Web of Science databases for articles published between December 1994 and September 2023 was performed. Out of the initial 2510 studies identified, 17 articles were retrieved that met all the predetermined selection criteria, particularly of assessing qEEG changes in one of the three conditions compared to healthy controls. All studies scored moderate to high quality on the Newcastle-Ottawa scale. There was a general trend for decreased low-frequency EEG band activity (delta, theta, and alpha) and increased high-frequency EEG beta activity in FMS, differing to that found in ME/CFS. The limited LC studies included in this review focused mainly on cognitive impairments and showed mixed findings not consistent with patterns observed in FMS and ME/CFS. Our findings suggest different patterns of qEEG brainwave activity in FMS and ME/CFS. Further research is required to explore whether there are phenotypes within LC that have EEG signatures similar to FMS or ME/CFS. This could inform identification of reliable diagnostic markers and possible targets for neuromodulation therapies tailored to each clinical syndrome. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Practical relevance: Chronic pain is a significant welfare concern in cats, and neuropathic pain, which arises from aberrant processing of sensory signals within the nervous system, is a subcategory of this type of pain. To comprehend this condition and how multimodal pharmacotherapy plays a central role in alleviating discomfort, it is crucial to delve into the anatomy of nociception and pain perception. In addition, there is an intricate interplay between emotional health and chronic pain in cats, and understanding and addressing the emotional factors that contribute to pain perception, and vice versa, is essential for comprehensive care. Clinical approach: Neuropathic pain is suspected if there is abnormal sensation in the area of the distribution of pain, together with a positive response to trial treatment with drugs effective for neuropathic pain. Ideally, this clinical suspicion would be supported by confirmation of a lesion at this neurolocalisation using diagnostic modalities such as MRI and neuroelectrophysiology. Alternatively, there may be a history of known trauma at that site. A variety of therapies, including analgesic, anti-inflammatory and adjuvant drugs, and neuromodulation (eg, TENS or acupuncture), can be employed to address different facets of pain pathways. Aim: This review article, aimed at primary care/ general practitioners, focuses on the identification and management of neuropathic pain in cats. Three case vignettes are included and a structured treatment algorithm is presented to guide veterinarians in tailoring interventions. Evidence base: The review draws on current literature, where available, along with the author's extensive experience and research. [ABSTRACT FROM AUTHOR]

Purpose: To translate and cross-culturally adapt the English version of the Central Sensitisation Inventory (CSI) into Thai (CSI-Thai) and to evaluate its psychometric properties in individuals with chronic non-specific neck pain. Materials and methods: Cross-cultural translation and adaptation of the CSI were performed according to standard guidelines. A total of 340 participants were invited to complete the CSI-Thai, Visual Analogue Scale (pain intensity), Neck Disability Index, Fear-Avoidance Beliefs Questionnaire, Pain Catastrophising Scale (PCS), and Short Form-36. Psychometric evaluation included confirmatory factor analysis, internal consistency, test-retest reliability, agreement, and construct validity. Results: Dimensionality analyses indicated that a bifactor model, comprising one general factor plus four orthogonal factors, fit the CSI structure better than unidimensional and the four-factor models. The general factor showed substantial reliability (Cronbach α=0.91, Omega ω=0.94, and omega hierarchical x-h=0.91). The intraclass correlation coefficient was 0.90, representing excellent stability over a 48 h interval. Moderate-to-strong correlations and acceptable-to-excellent discriminations were found between the CSI-Thai and all questionnaires. The exception was the PCS (no correlation and discrimination). The standard error of measurement and minimal detectable change of the CSI-Thai were 2.33 and 6.47, respectively. Conclusions: The translation and cross-cultural adaptation of the CSI-Thai were successful, with satisfactory reliability and construct validity. [ABSTRACT FROM AUTHOR]

Social support has been shown to reduce pain ratings and physiological responses to acute pain stimuli. Furthermore, this relationship is moderated by adult attachment styles. However, these effects have not been characterized in experimentally induced symptoms of chronic pain, such as secondary hyperalgesia (SH) which is characterized by an increased sensitivity of the skin surrounding an injury. We aimed to examine whether social support by handholding from a romantic partner can attenuate the development of experimentally induced SH. Thirty-seven women, along with their partners, participated in 2 experimental sessions 1 week apart. In both sessions, SH was induced using an electrical stimulation protocol. In the support condition, the partner was seated across from the participant holding the participant’s hand during the electrical stimulation, whereas in the alone condition, the participant went through the stimulation alone. Heart rate variability was measured for both the participant as well as the partner before, during, and after the stimulation. We found that the width of the area of hyperalgesia was significantly smaller in the support condition. Attachment styles did not moderate this effect of social support on the area width. Increasing attachment avoidance was associated with both a smaller width of hyperalgesia and a smaller increase in the sensitivity on the stimulated arm. For the first time, we show that social support can attenuate the development of secondary hyperalgesia and that attachment avoidance may be associated with an attenuated development of secondary hyperalgesia. [ABSTRACT FROM AUTHOR]

Introduction: The mechanism underlying endometriosis‐related pain remains poorly understood. Previous studies have indicated that γ‐aminobutyric acid (GABA) type A (GABAA) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABAA receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABAA receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relation between GABAA receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABAA receptor, in the participating women. Material and methods: 15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom‐free, control women, aged 18–40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection. Results: Compared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABAA receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels. Conclusions: Women with painful endometriosis show altered GABAA receptor function, depicted as a muted response to an exogenous GABAA receptor agonist. [ABSTRACT FROM AUTHOR]

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.

'Non-inflammatory' pain, pain that is not associated with measures of inflammation, is common in patients with inflammatory arthritis including RA. One important cause of non-inflammatory pain is concomitant fibromyalgia. Systematic review has shown that fibromyalgia is common in inflammatory arthritis including RA affecting 1 in 5 patients and is associated with higher disease activity scores due to inflated tender joint count and patient global assessment. Consequently, many patients with RA and concomitant fibromyalgia may fail to reach treatment target and switch to alternate disease modifying drugs frequently. European Alliance of Association for Rheumatology has highlighted that concomitant fibromyalgia is an important consideration in assessing difficult-to-treat RA. The incidence and prevalence of fibromyalgia are higher in RA than the general population, raising the possibility that fibromyalgia may be 'secondary' to RA rather than a concomitant disease. The precise mechanisms whereby patients with RA develop fibromyalgia are unknown. In this review, we discussed fibromyalgia in RA, its clinical impact and epidemiology as well as data suggesting fibromyalgia might be 'secondary'. Lastly, we reviewed potential pathogenic mechanisms which included inflammatory cytokines sensitizing nociceptive neurones, temporal summation, also known as windup, from chronic pain and impaired coping from poor quality sleep and mental well-being. Deciphering the exact mechanisms may lead to treatment strategies that prevent development of secondary fibromyalgia and will address a common factor associated with difficult-to-treat RA. [ABSTRACT FROM AUTHOR]

Background: Rotator cuff‐related shoulder pain (RCRSP) was proposed to have a complex pain mechanism, but the exact aetiology is still unclear. A recent review summarised the updated research to analyse the traditional concept of shoulder impingement which may not be accurate. Current studies have demonstrated that mechanical factors including a reduction in subacromial space, scapular dyskinesia and different acromial shapes are unlikely directly contributing to RCRSP. Aims: Since the precise RCRSP pain mechanism remains unclear, the aim of this narrative review is to discuss possible sources of pain contributing to RCRSP according to the mechanisms‐based pain classifications. Results and Discussion: Research findings on potential mechanical nociceptive factors of RCRSP are conflicting; investigations of neuropathic and central pain mechanisms of RCRSP are limited and inconclusive. Overall, available evidence has indicated moderate to strong correlations between RCRSP and chemical nociceptive sources of pain. Conclusion: Results from current research may provide new directions for future studies on the aetiology of RCRSP and its clinical management towards a biochemical view instead of the traditional mechanical hypothesis. [ABSTRACT FROM AUTHOR]

Introduction The pathophysiology of fibromyalgia (FM) is related to central sensitisation (CS) to pain. Algometry allows assessing CS based on dynamic evoked pain. However, current algometrýs protocols require optimising, unifying and updating.Objectives 1) identify the dynamic pain measures used most frequently to effectively assess CS processes in FM, and 2) consider the future of the algometry assessing CS in these patients.Methods Cochrane Collaboration guidelines and PRISMA statements were followed. The protocol was registered in PROSPERO database (ID: CRD42021270135). The selected articles were evaluated using the Cochrane risk of bias (ROB) assessment tool. The PubMed, Scopus, and Web of Science databases were searched.Results Thirty-four studies were selected, including measures such as temporal summation of pain (TSP), aftersensations (AS), spatial summation of pain (SSP), the noxious flexion reflex (NFR) threshold, conditioned pain modulation (CPM), cutaneous silent period (CuSP), and slowly repeated evoked pain (SREP); and evoked pain combined with neuroimaging. Each measure offered various advantages and limitations. According to ROB, 28 studies were of low quality, 3 of moderate quality, and 3 of high quality.Conclusions Several pain indicators have been demonstrated to successfully examine CS involvement in FM in the last years. Algometry, especially when it involves diverse body sites and tissues, might provide further insight into (1) the evaluation of psychological factors known to influence pain experience, (2) new dynamic pain indicators, and (3) the simultaneous use of certain neuroimaging techniques. Further research clarifying the mechanisms underlying some of these measures, and homogenisation and optimisation of the algometrýs protocols, are needed. KEY MESSAGESAlgometry allows for assessing Central Sensitisation by applying dynamic evoked pain.The future of algometry could relapse in its combination with neuroimaging.Recently-emerged pain indicators should be considered for algometrýs new protocols.

Abstract Objectives Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a debilitating condition characterised by bladder/pelvic pain and pressure as well as persistent or recurrent urinary symptoms in the absence of an identifiable cause. It is hypothesised that in addition to organ specific visceral hypersensitivity, contributions of the hypertonic pelvic floor, peripheral sensitisation, and central sensitisation exacerbate this condition. The aim of this paper is to investigate outcomes of treating underlying neuromuscular dysfunction and neuro‐plastic mechanisms in BPS/IC patients. Methods A retrospective chart review of 84 patients referred to an outpatient pelvic rehabilitation centre with a diagnosis of BPS/IC given to them by a urologist. All 84 patients failed to progress after completing 6 weeks of pelvic floor physical therapy and underwent an institutional review board approved protocol (IRB# 17‐0761) consisting of external ultrasound‐guided trigger point injections to the pelvic floor musculature, peripheral nerve blocks of the pudendal and posterior femoral cutaneous nerves and continued pelvic floor physical therapy once weekly for 6 weeks. Pelvic pain intensity and functionality were measured pretreatment and 3 months posttreatment using Visual Analogue Scale (VAS) and Functional Pelvic Pain Scale (FPPS). Results Pretreatment, mean VAS was 6.23 ± 2.68 (95% CI 5.65 to 6.80). Posttreatment mean VAS was 3.90 ± 2.63 (95% CI 3.07–4.74). Mean FPPS before treatment was 11.98 ± 6.28 (95% CI 10.63 to 13.32). Posttreatment mean FPPS was 7.68 ± 5.73 (95% CI 6.45–8.90). Analysis of subcategories within FPPS indicated highest statistically significant improvement in the categories of bladder, intercourse and working. Conclusions Analysis suggests the treatment was effective at ameliorating bladder pain and function including urinary urgency, frequency, and burning in BPS/IC patients.

Nociplastic pain syndromes include particular fibromyalgia, irritable bowel syndrome, headache, complex regional pain syndrome, and idiopathic orofacial pain. Several mechanisms have been proposed to account for nociplastic pain including central sensitisation, alterations of pain modulatory controls, epigenetic changes, and peripheral mechanisms. Importantly, nociplastic pain might also be present in patients with cancer pain, particularly those with pain related to complications of cancer treatment. Increased awareness of nociplastic pain associated with cancer should have important implications for monitoring and managing such patients. [ABSTRACT FROM AUTHOR]

Pain after cancer remains underestimated and undertreated. Precision medicine is a recent concept that refers to the ability to classify patients into subgroups that differ in their susceptibility to, biology, or prognosis of a particular disease, or in their response to a specific treatment, and thus to tailor treatment to the individual patient characteristics. Applying this to pain after cancer, the ability to classify post-cancer pain into the three major pain phenotypes (i.e. nociceptive, neuropathic, and nociplastic pain) and tailor pain treatment accordingly, is an emerging issue. This is especially relevant because available evidence suggests that nociplastic pain is present in an important subgroup of those patients experiencing post-cancer pain. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system for nociplastic pain account for the need to identify and correctly classify patients according to the pain phenotype early in their treatment. These criteria are an important step towards precision pain medicine with great potential for the field of clinical oncology. Within this framework, the Cancer Pain Phenotyping (CANPPHE) Network, an international and interdisciplinary group of oncology clinicians and researchers from seven countries, applied the 2021 IASP clinical criteria for nociplastic pain to the growing population of those experiencing post-cancer pain. A manual is provided to allow clinicians to differentiate between predominant nociceptive, neuropathic, or nociplastic pain after cancer. A seven-step diagnostic approach is presented and illustrated using cases to enhance understanding and encourage effective implementation of this approach in clinical practice. [ABSTRACT FROM AUTHOR]

Summary: Identifying factors associated with persistent pain after breast cancer surgery may facilitate risk stratification and individualised management. Single‐population studies have limited generalisability as socio‐economic and genetic factors contribute to persistent pain development. Therefore, this prospective multicentre cohort study aimed to develop a predictive model from a sample of Asian and American women. We enrolled women undergoing elective breast cancer surgery at KK Women's and Children's Hospital and Duke University Medical Center. Pre‐operative patient and clinical characteristics and EQ‐5D‐3L health status were recorded. Pain catastrophising scale; central sensitisation inventory; coping strategies questionnaire‐revised; brief symptom inventory‐18; perceived stress scale; mechanical temporal summation; and pressure‐pain threshold assessments were performed. Persistent pain was defined as pain score ≥ 3 or pain affecting activities of daily living 4 months after surgery. Univariate associations were generated using generalised estimating equations. Enrolment site was forced into the multivariable model, and risk factors with p < 0.2 in univariate analyses were considered for backwards selection. Of 210 patients, 135 (64.3%) developed persistent pain. The multivariable model attained AUC = 0.807, with five independent associations: age (OR 0.85 95%CI 0.74–0.98 per 5 years); diabetes (OR 4.68, 95%CI 1.03–21.22); pre‐operative pain score at sites other than the breast (OR 1.48, 95%CI 1.11–1.96); previous mastitis (OR 4.90, 95%CI 1.31–18.34); and perceived stress scale (OR 1.35, 95%CI 1.01–1.80 per 5 points), after adjusting for: enrolment site; pre‐operative pain score at the breast; pre‐operative overall pain score at rest; postoperative non‐steroidal anti‐inflammatory drug use; and pain catastrophising scale. Future research should validate this model and evaluate pre‐emptive interventions to reduce persistent pain risk. [ABSTRACT FROM AUTHOR]

Fibromyalgia is characterised by widespread musculoskeletal pain, which may present with fatigue, depression, anxiety, sleep and cognitive disturbances. It is the second most prevalent rheumatic disease. An accurate diagnosis is challenging, since its symptoms may resemble diverse conditions such as carpal tunnel syndrome, Raynaud syndrome, Sjögren syndrome, amongst others. Neuropathic pain and autonomic dysfunction in fibromyalgia suggest the involvement of the nervous system. Ion channels, neurotransmitters and neuromodulators may play a role. Small fibre neuropathy (SFN) may also cause chronic widespread pain. SFN may occur in 50% of fibromyalgia patients, but its role in the disease is unknown. Despite several efforts to synthesise the evidence on the mechanisms for pain in fibromyalgia, there are few studies applying an integrative perspective of neurochemical, immunological, and neuroanatomical characteristics, and their relevance to the disease. This protocol aims to clarify the mechanisms of the central and peripheral nervous system associated with pain in fibromyalgia. We will retrieve published studies from Web of Science, MEDLINE, Scopus, EBSCOhost, Ovid and Google Scholar. All clinical studies or experimental models of fibromyalgia reporting imaging, neurophysiological, anatomical, structural, neurochemical, or immunological characteristics of the central or peripheral nervous systems associated with pain will be included. Exclusion criteria will eliminate studies evaluating pain without a standardised measure, studies written in languages different from Spanish or English that could not be appropriately translated, and studies whose full-text files could not be retrieved after all efforts made. A narrative synthesis will be performed. [ABSTRACT FROM AUTHOR]

Background: Experienced assessors show good intra-rater reproducibility (withinsession and between-session agreement and reliability) when using an algometer to determine pressure pain thresholds (PPT). However, it is unknown whether novice assessors perform equally well. This study aimed to determine within and between-session agreement and reliability of PPT measurements performed by novice assessors and explored whether these parameters differed per assessor and algometer type. Methods: Ten novice assessors measured PPTs over four test locations (tibialis anterior muscle, rectus femoris muscle, extensor carpi radialis brevis muscle and paraspinal muscles C5-C6) in 178 healthy participants, using either a Somedic Type II digital algometer (10 raters; 88 participants) or a Wagner Force Ten FDX 25 digital algometer (nine raters; 90 participants). Prior to the experiment, the novice assessors practiced PPTs for 3 h per algometer. Each assessor measured a different subsample of ~9 participants. For both the individual assessor and for all assessors combined (i.e., the group representing novice assessors), the standard error of measurement (SEM) and coefficient of variation (CV) were calculated to reflect within and between-session agreement. Reliability was assessed using intraclass correlation coefficients (ICC1,1). Results: Within-session agreement expressed as SEM ranged from 42 to 74 kPa, depending on the test location and device. Between-session agreement, expressed as SEM, ranged from 36 to 76 kPa and the CV ranged from 9-16% per body location. Individual assessors differed from the mean group results, ranging from -55 to +32 kPa or from -9.5 to +6.6 percentage points. Reliability was good to excellent (ICC1,1: 0.87 to 0.95). Results were similar for both types of algometers. Conclusions: Following 3 h of algometer practice, there were slight differences between assessors, but reproducibility in determining PPTs was overall good. [ABSTRACT FROM AUTHOR]

The pathophysiology of fibromyalgia (FM) is related to central sensitisation (CS) to pain. Algometry allows assessing CS based on dynamic evoked pain. However, current algometrýs protocols require optimising, unifying and updating. 1) identify the dynamic pain measures used most frequently to effectively assess CS processes in FM, and 2) consider the future of the algometry assessing CS in these patients. Cochrane Collaboration guidelines and PRISMA statements were followed. The protocol was registered in PROSPERO database (ID: CRD42021270135). The selected articles were evaluated using the Cochrane risk of bias (ROB) assessment tool. The PubMed, Scopus, and Web of Science databases were searched. Thirty-four studies were selected, including measures such as temporal summation of pain (TSP), aftersensations (AS), spatial summation of pain (SSP), the noxious flexion reflex (NFR) threshold, conditioned pain modulation (CPM), cutaneous silent period (CuSP), and slowly repeated evoked pain (SREP); and evoked pain combined with neuroimaging. Each measure offered various advantages and limitations. According to ROB, 28 studies were of low quality, 3 of moderate quality, and 3 of high quality. Several pain indicators have been demonstrated to successfully examine CS involvement in FM in the last years. Algometry, especially when it involves diverse body sites and tissues, might provide further insight into (1) the evaluation of psychological factors known to influence pain experience, (2) new dynamic pain indicators, and (3) the simultaneous use of certain neuroimaging techniques. Further research clarifying the mechanisms underlying some of these measures, and homogenisation and optimisation of the algometrýs protocols, are needed. Algometry allows for assessing Central Sensitisation by applying dynamic evoked pain. The future of algometry could relapse in its combination with neuroimaging. Recently-emerged pain indicators should be considered for algometrýs new protocols. [ABSTRACT FROM AUTHOR]

Abstract Background Autistic adults, particularly women, are more likely to experience chronic ill health than the general population. Central sensitivity syndromes (CSS) are a group of related conditions that are thought to include an underlying sensitisation of the central nervous system; heightened sensory sensitivity is a common feature. Anecdotal evidence suggests autistic adults may be more prone to developing a CSS. This study aimed to investigate the occurrence of CSS diagnoses and symptoms in autistic adults, and to explore whether CSS symptoms were related to autistic traits, mental health, sensory sensitivity, or gender. Methods The full sample of participants included 973 autistic adults (410 men, 563 women, mean age = 44.6) registered at the Netherlands Autism Register, who completed questionnaires assessing autistic traits, sensory sensitivity, CSS, physical and mental health symptoms. The reliability and validity of the Central Sensitization Inventory (CSI) in an autistic sample was established using exploratory and confirmatory factor analyses. Chi2 analyses, independent t-tests, hierarchical regression and path analysis were used to analyse relationships between CSS symptoms, autistic traits, measures of mental health and wellbeing, sensory sensitivity, age and gender. Results 21% of participants reported one or more CSS diagnosis, and 60% scored at or above the clinical cut-off for a CSS. Autistic women were more likely to report a CSS diagnosis and experienced more CSS symptoms than men. Sensory sensitivity, anxiety, age and gender were significant predictors of CSS symptoms, with sensory sensitivity and anxiety fully mediating the relationship between autistic traits and CSS symptoms. Limitations Although this study included a large sample of autistic adults, we did not have a control group or a CSS only group. We also could not include a non-binary group due to lack of statistical power. Conclusions CSS diagnoses and symptoms appear to be very common in the autistic population. Increased awareness of an association between autism and central sensitisation should inform clinicians and guide diagnostic practice, particularly for women where CSS are common and autism under recognised.

Background Experienced assessors show good intra-rater reproducibility (within-session and between-session agreement and reliability) when using an algometer to determine pressure pain thresholds (PPT). However, it is unknown whether novice assessors perform equally well. This study aimed to determine within and between-session agreement and reliability of PPT measurements performed by novice assessors and explored whether these parameters differed per assessor and algometer type. Methods Ten novice assessors measured PPTs over four test locations (tibialis anterior muscle, rectus femoris muscle, extensor carpi radialis brevis muscle and paraspinal muscles C5-C6) in 178 healthy participants, using either a Somedic Type II digital algometer (10 raters; 88 participants) or a Wagner Force Ten FDX 25 digital algometer (nine raters; 90 participants). Prior to the experiment, the novice assessors practiced PPTs for 3 h per algometer. Each assessor measured a different subsample of ~9 participants. For both the individual assessor and for all assessors combined (i.e., the group representing novice assessors), the standard error of measurement (SEM) and coefficient of variation (CV) were calculated to reflect within and between-session agreement. Reliability was assessed using intraclass correlation coefficients (ICC1,1). Results Within-session agreement expressed as SEM ranged from 42 to 74 kPa, depending on the test location and device. Between-session agreement, expressed as SEM, ranged from 36 to 76 kPa and the CV ranged from 9–16% per body location. Individual assessors differed from the mean group results, ranging from −55 to +32 kPa or from −9.5 to +6.6 percentage points. Reliability was good to excellent (ICC1,1: 0.87 to 0.95). Results were similar for both types of algometers. Conclusions Following 3 h of algometer practice, there were slight differences between assessors, but reproducibility in determining PPTs was overall good.

Objective: Emerging evidence suggests that individual levels of sensory sensitivity may impact treatment outcomes for people recovering from burn injuries. For example, individuals with higher levels of sensory sensitivity were less adherent with compression garment wear, often used for scar management. The purpose of this study was to characterise sensory patterns for a sample of burn-injured patients as a cohort, using normative data as the reference. As different patterns of sensory processing can have implications clinically, understanding this at the cohort level may provide valuable insight for therapy.Method: This was a secondary analysis of data collected during a cross-sectional study. Adults (N = 117) attending the Professor Stuart Pegg Adult Burns Unit outpatient clinic completed the Adolescent/Adult Sensory Profile and the following quantitative sensory tests: two-point discrimination; mechanical detection threshold; and pressure pain threshold.Results: Compared to matched normative data, burn-injured patients reported higher levels of sensory sensitive and avoiding patterns, and experienced lower detection thresholds for touch and pain.Conclusions: Higher reports of sensory sensitivity and sensory avoiding, and lower thresholds for touch and pain, have been correlated with tactile defensiveness. Tactile defensiveness has been associated with social withdrawal and isolation, all of which could contribute to decreased engagement in therapy. The ways in which these sensory characteristics impact on burn-related treatments, such as compression garment adherence, warrant further investigation. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study is to evaluate the presence and frequency of central sensitisation (CS) in primary Sjögren Syndrome (pSS) and to determine the effect of CS on sleep quality. Materials and Methods: In this cross-sectional study, 50 patients diagnosed with pSS between the ages of 18 and 75 were included. The healthy control group was composed of 43 healthcare workers. Each participant underwent a physical examination, and demographic data and the medications they used were recorded. Central sensitisation inventory and Pittsburgh Sleep Quality Index questionnaires were filled in to garner data on CS and sleep quality, respectively, from all participants. Results: While central sensitisation inventory >40 was detected in 74% of pSS patients, it was 25.6% in healthy controls, and there is a statistically significant difference between the groups (p < .05). A correlation analysis of the central sensitisation inventory and Pittsburgh Sleep Quality Index values of all participants revealed a statistically significant correlation between all parameters other than the duration of sleep (p < .05). Conclusions: CS was found to have a negative effect on sleep quality in patients with pSS. We suggest that the cause of widespread pain seen in patients with pSS as the possible development of CS should be considered. [ABSTRACT FROM AUTHOR]

Background: Pain, the primary complaint in rheumatoid arthritis (RA), is multifaceted, and may be driven by inflammatory disease activity and central sensitisation. We aimed to ascertain what proportion of RA pain severity is explained by markers of inflammation and quantitative sensory testing (QST) indices of central sensitisation., Methods: This was a cross-sectional analysis of data from individuals with clinically active RA. Pain severity was assessed using numerical rating scales and inflammation via 28-joint Disease Activity Score (DAS28) and Ultrasound (Greyscale, Power Doppler). Pain sensitivity was assessed by 'static' (tibialis anterior or brachioradialis pressure pain detection threshold-PPT-TA/PPT-BR) and 'dynamic' (temporal summation-TS, conditioned pain modulation-CPM) QST. Bivariate associations used Spearman's correlation coefficients, and multivariable linear regression models determined relative contributions to pain severity., Results: In bivariate analyses of N = 96 (age 65 ± 10y, 77% females) people with RA, pain severity was significantly associated with inflammation indices (r = 0.20 to 0.55), and CPM (r=-0.26). In multivariable models that included TS, CPM, age, sex, and body mass index, inflammation indices remained significantly associated with pain severity. Multivariable models explained 22 to 27% of pain variance. Heterogeneity was apparent for associations with pain between subscores for pain now, strongest or average over the past 4-weeks., Conclusions: In individuals with clinically active RA, markers of inflammatory disease activity best explain RA pain with only marginal contributions from QST indices of central sensitisation. Although inflammation plays a key role in the experience of RA pain, the greater proportion of pain severity remains unexplained by DAS28 and ultrasound indices of inflammation., (© 2024. The Author(s).)

Background: The STarT Back Screening Tool (SBT) is recommended to provide risk-stratified care in low back pain (LBP), yet its predictive value is moderate for disability and low for pain severity. Assessment of human assumed central sensitisation (HACS) in conjunction with the SBT may improve its predictive accuracy., Objectives: To examine whether assessment of HACS in acute LBP improves the predictive accuracy of the SBT for LBP recovery at six months in people with acute non-specific LBP., Design: A prospective longitudinal study., Method: Data were drawn from the UPWaRD study. One hundred and twenty people with acute non-specific LBP were recruited from the community. Baseline measures included SBT risk status, nociceptive flexor withdrawal reflex, pressure and heat pain thresholds and conditioned pain modulation. Primary outcome was the presence of LBP (pain numeric rating scale ≥1 and Roland Morris Disability Questionnaire score ≥3) at six-month follow-up. Regression coefficients were penalised using the least absolute shrinkage and selection operator technique to select predictor variables. Internal validation was performed using ten-fold cross-validation., Results/findings: SBT risk status alone did not predict the presence of LBP at six months (area under receiver operating characteristic curve [AUC] = 0.58). Adding measures of HACS to the SBT did not improve discrimination for whether LBP was present at six months (AUC = 0.59)., Conclusions: This study confirmed the suboptimal predictive accuracy of the SBT, administered during acute LBP, for LBP recovery at six months. Assessment of HACS in acute LBP does not improve the predictive accuracy of the SBT., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Pain after resolution of peripheral nerve block, known as 'rebound pain' (RP), is a major problem in outpatient surgery. The primary objective was to evaluate the benefit of intraoperative ketamine at an anti-hyperalgesic dose on the incidence of rebound pain after upper limb surgery under axillary plexus block in ambulatory patients. The secondary objective was to better understand the rebound pain phenomenon (individual risk factors).Methods: In this prospective, double-blind study, patients were randomised to receive either a single dose of i.v. ketamine (0.3 mg kg-1) or a placebo. Preoperative mechanical temporal summation and central sensitization inventory were applied to question underlying central sensitisation. Pain catastrophising and Douleur Neuropathique 4 questionnaires were used. Rebound pain was defined as pain intensity score >7 (numeric rating scale, 0-10) after block resolution. Postoperative pain was recorded at Days 1, 4, and 30 after discharge.Results: A total of 109 subjects completed the study, and 40.4% presented with rebound pain. Ketamine administration did not reduce rebound pain incidence or intensity. Temporal summation and central sensitisation inventory scores did not differ between subjects with and without rebound pain. The predictive risk factors were bone surgery (odds ratio [OR]=5.2; confidence interval [CI], 1.9-14.6), severe preoperative pain (OR=4.2; CI, 1.5-11.7), and high pain catastrophising (OR=4.8; CI, 1.0-22.3). At Day 30, the average daily pain was higher in the rebound pain group involving neuropathic characteristics.Conclusion: Ketamine at an anti-hyperalgesic dose showed no benefit on rebound pain development. Although central sensitisation might not be involved, preoperative pain intensity, and catastrophising stand as risk factors. Because rebound pain remains frequent despite adequate procedure-specific postoperative analgesia, future studies should focus on patient-specific pain management. [ABSTRACT FROM AUTHOR]

Background: Autistic adults, particularly women, are more likely to experience chronic ill health than the general population. Central sensitivity syndromes (CSS) are a group of related conditions that are thought to include an underlying sensitisation of the central nervous system; heightened sensory sensitivity is a common feature. Anecdotal evidence suggests autistic adults may be more prone to developing a CSS. This study aimed to investigate the occurrence of CSS diagnoses and symptoms in autistic adults, and to explore whether CSS symptoms were related to autistic traits, mental health, sensory sensitivity, or gender. Methods: The full sample of participants included 973 autistic adults (410 men, 563 women, mean age = 44.6) registered at the Netherlands Autism Register, who completed questionnaires assessing autistic traits, sensory sensitivity, CSS, physical and mental health symptoms. The reliability and validity of the Central Sensitization Inventory (CSI) in an autistic sample was established using exploratory and confirmatory factor analyses. Chi2 analyses, independent t-tests, hierarchical regression and path analysis were used to analyse relationships between CSS symptoms, autistic traits, measures of mental health and wellbeing, sensory sensitivity, age and gender. Results: 21% of participants reported one or more CSS diagnosis, and 60% scored at or above the clinical cut-off for a CSS. Autistic women were more likely to report a CSS diagnosis and experienced more CSS symptoms than men. Sensory sensitivity, anxiety, age and gender were significant predictors of CSS symptoms, with sensory sensitivity and anxiety fully mediating the relationship between autistic traits and CSS symptoms. Limitations: Although this study included a large sample of autistic adults, we did not have a control group or a CSS only group. We also could not include a non-binary group due to lack of statistical power. Conclusions: CSS diagnoses and symptoms appear to be very common in the autistic population. Increased awareness of an association between autism and central sensitisation should inform clinicians and guide diagnostic practice, particularly for women where CSS are common and autism under recognised. [ABSTRACT FROM AUTHOR]

Aims: Diabetic peripheral neuropathy (DPN) occurs in about half of people with diabetes, of whom a quarter may develop chronic pain. Pain may remain for years yet be difficult to treat because the underlying mechanisms remain unclear. There is consensus that processing excessive glucose leads to oxidative stress, interfering with normal metabolism. In this narrative review, we argue that oxidative stress may also contribute to pain. Methods: We reviewed literature in PubMed published between January 2005 and August 2021. Results and conclusions: In diabetes, hyperglycaemia and associated production of reactive species can directly increase pain signalling and activate sensory neurons; or the effects can be indirect, mediated by mitochondrial damage and enhanced inflammation. Furthermore, pain processing in the central nervous system is compromised in painful DPN. This is implicated in central sensitisation and dysfunctional pain modulation. However, central pain modulatory function is understudied in diabetes. Future research is required to clarify whether central sensitisation and/or disturbances in central pain modulation contribute to painful DPN. Positive results would facilitate early detection and future treatment. [ABSTRACT FROM AUTHOR]

Persistence of low back pain is thought to be associated with different underlying pain mechanisms, including ongoing nociceptive input and central sensitisation. We hypothesised that primary motor cortex (M1) representations of back muscles (a measure of motor system adaptation) would differ between pain mechanisms, with more consistent observations in individuals presumed to have an ongoing contribution of nociceptive input consistently related to movement/posture. We tested 28 participants with low back pain sub‐grouped by the presumed underlying pain mechanisms: nociceptive pain, nociplastic pain and a mixed group with features consistent with both. Transcranial magnetic stimulation was used to study M1 organisation of back muscles. M1 maps of multifidus (deep and superficial) and longissimus erector spinae were recorded with fine‐wire electromyography and thoracic erector spinae with surface electromyography. The nociplastic pain group had greater variability in M1 map location (centre of gravity) than other groups (p <.01), which may suggest less consistency, and perhaps relevance, of motor cortex adaptation for that group. The mixed group had greater overlap of M1 representations between deep/superficial muscles than nociceptive pain (deep multifidus/longissimus: p =.001, deep multifidus/thoracic erector spinae: p =.008) and nociplastic pain (deep multifidus/longissimus: p =.02, deep multifidus/thoracic erector spinae: p =.02) groups. This study provides preliminary evidence of differences in M1 organisation in subgroups of low back pain classified by likely underlying pain mechanisms. Despite the sample size, differences in cortical re‐organisation between subgroups were detected. Differences in M1 organisation in subgroups of low back pain supports tailoring of treatment based on pain mechanism and motor adaptation. [ABSTRACT FROM AUTHOR]

Background. Conditioned pain modulation (CPM) is measured by comparing pain induced by a test stimulus with pain induced by the same test stimulus, either during (parallel design) or after (sequential design) the conditioning stimulus. Whether design, conditioning stimulus intensity and test stimulus selection affect CPM remains unclear. Methods. CPM effects were evaluated in healthy participants (N D 89) at the neck, forearm and lower leg using the cold pressor test as the conditioning stimulus. In three separate experiments, we compared the impact of (1) design (sequential versus parallel), (2) conditioning stimulus intensity (VAS 40/100 versus VAS 60/100), and (3) test stimulus selection (single versus dual, i.e., mechanical and thermal). Statistical analyses of the main effect of design (adjusted for order) and experiment were conducted using linear mixed models with random intercepts. Results. No significant differences were identified in absolute CPM data. In relative CPM data, a sequential design resulted in a slightly lower CPM effect compared to a parallel design, and only with a mechanical test stimulus at the neck (-6.1%; 95% CI [-10.1 to -2.1]) and lower leg (-5.9%; 95% CI [-11.7 to -0.1]) but not forearm (-4.5%; 95% CI [-9.0 to 0.1]). Conditioning stimulus intensity and test stimulus selection did not influence the CPM effect nor the difference in CPM effects derived from parallel versus sequential designs. Conclusions. Differences in CPM effects between protocols were minimal or absent. A parallel design may lead to a minimally higher relative CPM effect when using a mechanical test stimulus. The conditioning stimulus intensities assessed in this study and performing two test stimuli did not substantially influence the differences between designs nor the magnitude of the CPM effect. [ABSTRACT FROM AUTHOR]

Background Conditioned pain modulation (CPM) is measured by comparing pain induced by a test stimulus with pain induced by the same test stimulus, either during (parallel design) or after (sequential design) the conditioning stimulus. Whether design, conditioning stimulus intensity and test stimulus selection affect CPM remains unclear. Methods CPM effects were evaluated in healthy participants (N = 89) at the neck, forearm and lower leg using the cold pressor test as the conditioning stimulus. In three separate experiments, we compared the impact of (1) design (sequential versus parallel), (2) conditioning stimulus intensity (VAS 40/100 versus VAS 60/100), and (3) test stimulus selection (single versus dual, i.e., mechanical and thermal). Statistical analyses of the main effect of design (adjusted for order) and experiment were conducted using linear mixed models with random intercepts. Results No significant differences were identified in absolute CPM data. In relative CPM data, a sequential design resulted in a slightly lower CPM effect compared to a parallel design, and only with a mechanical test stimulus at the neck (−6.1%; 95% CI [−10.1 to −2.1]) and lower leg (−5.9%; 95% CI [−11.7 to −0.1]) but not forearm (−4.5%; 95% CI [−9.0 to 0.1]). Conditioning stimulus intensity and test stimulus selection did not influence the CPM effect nor the difference in CPM effects derived from parallel versus sequential designs. Conclusions Differences in CPM effects between protocols were minimal or absent. A parallel design may lead to a minimally higher relative CPM effect when using a mechanical test stimulus. The conditioning stimulus intensities assessed in this study and performing two test stimuli did not substantially influence the differences between designs nor the magnitude of the CPM effect.

Background and Aims: Neuropathic-like pain, fatigue, cognitive difficulty, catastrophising, anxiety, sleep disturbance, depression, and widespread pain associate with a single factor in people with knee pain. We report the Central Aspects of Pain questionnaire (CAP) to characterise this across painful musculoskeletal conditions., Methods: CAP was derived from the 8 item CAP-Knee questionnaire, and completed by participants with joint pain in the Investigating Musculoskeletal Health and Wellbeing survey. Subgroups had osteoarthritis, back pain or fibromyalgia. Acceptability was evaluated by feedback and data missingness. Correlation coefficients informed widespread pain scoring threshold in relation to the other items, and evaluated associations with pain. Factor analysis assessed CAP structure. Intraclass Correlation Coefficient (ICC) between paper and electronic administration assessed reliability. Friedman test assessed score stability over 4 years in people reporting knee osteoarthritis., Results: Data were from 3579 participants (58% female, median age; 71 years), including subgroups with osteoarthritis (n = 1158), back pain (n = 1292) or fibromyalgia (n = 177). Across the 3 subgroups, ≥10/26 painful sites on the manikin scored widespread pain. Reliability was high (ICC= 0.89 (95% CI: 0.84-0.92)) and CAP scores fit to 1 and 2 factor model, with a total CAP score that was associated with pain severity and quality (r = 0.50-0.72). In people with knee pain, CAP scores were stable over 4 years at the group level, but displayed significant temporal heterogeneity within individual participants., Conclusions: Central Aspects of Pain is reliably measured by the CAP questionnaire across a range of painful musculoskeletal conditions, and is a changeable state., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Purpose: To translate and cross-culturally adapt the English version of the Central Sensitisation Inventory (CSI) into Thai (CSI-Thai) and to evaluate its psychometric properties in individuals with chronic non-specific neck pain., Materials and Methods: Cross-cultural translation and adaptation of the CSI were performed according to standard guidelines. A total of 340 participants were invited to complete the CSI-Thai, Visual Analogue Scale (pain intensity), Neck Disability Index, Fear-Avoidance Beliefs Questionnaire, Pain Catastrophising Scale (PCS), and Short Form-36. Psychometric evaluation included confirmatory factor analysis, internal consistency, test-retest reliability, agreement, and construct validity., Results: Dimensionality analyses indicated that a bifactor model, comprising one general factor plus four orthogonal factors, fit the CSI structure better than unidimensional and the four-factor models. The general factor showed substantial reliability (Cronbach α  = 0.91, Omega ω  = 0.94, and omega hierarchical ω - h  = 0.91). The intraclass correlation coefficient was 0.90, representing excellent stability over a 48 h interval. Moderate-to-strong correlations and acceptable-to-excellent discriminations were found between the CSI-Thai and all questionnaires. The exception was the PCS (no correlation and discrimination). The standard error of measurement and minimal detectable change of the CSI-Thai were 2.33 and 6.47, respectively., Conclusions: The translation and cross-cultural adaptation of the CSI-Thai were successful, with satisfactory reliability and construct validity.Implications for rehabilitationCentral Sensitisation Inventory-Thai version (CSI-Thai) is successfully adapted and demonstrated satisfactory reliability and construct validity.The CSI-Thai can be applicable to assess central sensitisation-related signs and symptoms in Thai-speaking patients with chronic non-specific neck pain (CNSNP) both clinical and research purposes.The CSI-Thai correlated to pain, disability and quality of life among patients with CNSNP.

Introduction: The mechanism underlying endometriosis-related pain remains poorly understood. Previous studies have indicated that γ-aminobutyric acid (GABA) type A (GABA A ) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABA A receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABA A receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relation between GABA A receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABA A receptor, in the participating women., Material and Methods: 15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom-free, control women, aged 18-40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection., Results: Compared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABA A receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels., Conclusions: Women with painful endometriosis show altered GABA A receptor function, depicted as a muted response to an exogenous GABA A receptor agonist., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Introduction: Central sensitisation (CS) can't be demonstrated and thus only be assumed to be present in humans: Human Assumed Central Sensitization (HACS)1. The Central Sensitisation Inventory (CSI)2 is a screening instrument for HACS with a cut-off score of 40 (range 0-100) 3. This study aims to re-establish the optimal cut-off value for the CSI and to study associated factors. Methods: Via ROC-analyses we compared patients with chronic pain with healthy controls. Regression analysis was performed on factors (descriptives; pain-related characteristics) possibly associated with CSI-score. Results: Based on patients (n = 1730) and controls (n = 250), CSI cut-off values for the presence of HACS were established at =30 (women: = 33; men: = 25(table)). Regression analyses showed that the CSI-score was associated with all factors (adjusted R2 = 54-58%). A low association between the CSI-score and pain severity was shown in women and men separately. Discussion: In contrast with previous studies, a lower cut-off score is established for patients with chronic pain, being higher for women than for men. Process evaluation: The question rises whether CSI should be used with a dichotomous, categorical or continuous scale. More insight is needed in the presence of HACS and, the influence of sex, other characteristics and specific sub-populations of patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study is to evaluate the presence and frequency of central sensitisation (CS) in primary Sjögren Syndrome (pSS) and to determine the effect of CS on sleep quality., Materials and Methods: In this cross-sectional study, 50 patients diagnosed with pSS between the ages of 18 and 75 were included. The healthy control group was composed of 43 healthcare workers. Each participant underwent a physical examination, and demographic data and the medications they used were recorded. Central sensitisation inventory and Pittsburgh Sleep Quality Index questionnaires were filled in to garner data on CS and sleep quality, respectively, from all participants., Results: While central sensitisation inventory  >40 was detected in 74% of pSS patients, it was 25.6% in healthy controls, and there is a statistically significant difference between the groups (p < .05). A correlation analysis of the central sensitisation inventory and Pittsburgh Sleep Quality Index values of all participants revealed a statistically significant correlation between all parameters other than the duration of sleep (p < .05)., Conclusions: CS was found to have a negative effect on sleep quality in patients with pSS. We suggest that the cause of widespread pain seen in patients with pSS as the possible development of CS should be considered., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a debilitating condition characterised by bladder/pelvic pain and pressure as well as persistent or recurrent urinary symptoms in the absence of an identifiable cause. It is hypothesised that in addition to organ specific visceral hypersensitivity, contributions of the hypertonic pelvic floor, peripheral sensitisation, and central sensitisation exacerbate this condition. The aim of this paper is to investigate outcomes of treating underlying neuromuscular dysfunction and neuro-plastic mechanisms in BPS/IC patients., Methods: A retrospective chart review of 84 patients referred to an outpatient pelvic rehabilitation centre with a diagnosis of BPS/IC given to them by a urologist. All 84 patients failed to progress after completing 6 weeks of pelvic floor physical therapy and underwent an institutional review board approved protocol (IRB# 17-0761) consisting of external ultrasound-guided trigger point injections to the pelvic floor musculature, peripheral nerve blocks of the pudendal and posterior femoral cutaneous nerves and continued pelvic floor physical therapy once weekly for 6 weeks. Pelvic pain intensity and functionality were measured pretreatment and 3 months posttreatment using Visual Analogue Scale (VAS) and Functional Pelvic Pain Scale (FPPS)., Results: Pretreatment, mean VAS was 6.23 ± 2.68 (95% CI 5.65 to 6.80). Posttreatment mean VAS was 3.90 ± 2.63 (95% CI 3.07-4.74). Mean FPPS before treatment was 11.98 ± 6.28 (95% CI 10.63 to 13.32). Posttreatment mean FPPS was 7.68 ± 5.73 (95% CI 6.45-8.90). Analysis of subcategories within FPPS indicated highest statistically significant improvement in the categories of bladder, intercourse and working., Conclusions: Analysis suggests the treatment was effective at ameliorating bladder pain and function including urinary urgency, frequency, and burning in BPS/IC patients., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Patients recovered from a COVID-19 infection often report vague symptoms of fatigue or dyspnoea, comparable to the manifestations in patients with central sensitisation. The hypothesis was that central sensitisation could be the underlying common aetiology in both patient populations. This study explored the presence of symptoms of central sensitisation, and the association with functional status and health-related quality of life, in patients post COVID-19 infection. Patients who were previously infected with COVID-19 filled out the Central Sensitisation Inventory (CSI), the Post-COVID-19 Functional Status (PCFS) Scale and the EuroQol with five dimensions, through an online survey. Eventually, 567 persons completed the survey. In total, 29.73% of the persons had a score of <40/100 on the CSI and 70.26% had a score of ≥40/100. Regarding functional status, 7.34% had no functional limitations, 9.13% had negligible functional limitations, 37.30% reported slight functional limitations, 42.86% indicated moderate functional limitations and 3.37% reported severe functional limitations. Based on a one-way ANOVA test, there was a significant effect of PCFS Scale group level on the total CSI score (F(4,486) = 46.17, p < 0.001). This survey indicated the presence of symptoms of central sensitisation in more than 70% of patients post COVID-19 infection, suggesting towards the need for patient education and multimodal rehabilitation, to target nociplastic pain. [ABSTRACT FROM AUTHOR]

Introduction: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are both complex conditions that are challenging to treat. This may be related to an incomplete understanding of their pathophysiology, itself obfuscated by their heterogeneity. The symptomatic overlap between them and their common comorbidity suggests a shared vulnerability, which might be explained by central sensitisation.Methods: 19 CFS cases, 19 FM cases and 20 age and sex matched healthy controls (HC) were recruited primarily from secondary care clinics in London. Those with other pain disorders, psychiatric diagnoses and those taking centrally acting or opiate medications were excluded. Participants were asked to abstain from alcohol and over the counter analgaesia 48 h prior to assessment by static and dynamic quantitative sensory tests, including measures of temporal summation (TS) and conditioned pain modulation (CPM).Results: CS, as defined by the presence of both enhanced TS and inefficient CPM, was present in 16 (84%) CFS cases, 18 (95%) FM cases, and none of the HC (p < 0.001). Pressure pain thresholds were lower in CFS (Median222kPaIQR 146-311; p = 0.04) and FM cases (Median 189 kPa; IQR 129-272; p = 0.003) compared to HC (Median 311 kPa; IQR 245-377). FM cases differed from HC in cold-induced (FM = 22.6 °C (15.3-27.7) vs HC = 14.2 °C (9.0-20.5); p = 0.01) and heat-induced (FM = 38.0 °C (35.2-44.0) vs HC = 45.3 °C (40.1-46.8); p = 0.03) pain thresholds, where CFS cases did not.Conclusion: Central sensitisation may be a common endophenotype in chronic fatigue syndrome and fibromyalgia. Further research should address whether central sensitisation is a cause or effect of these disorders. [ABSTRACT FROM AUTHOR]