Application of the IASP Grading System to Identify Underlying Pain Mechanisms in Patients with Knee Osteoarthritis: A Prospective Cohort Study.

OBJECTIVES: This study aimed to apply the International Association for the Study of Pain (IASP) grading system for identifying nociplastic pain in knee osteoarthritis (KOA) awaiting total knee arthroplasty (TKA) and propose criteria to finetune decision-making. Additionally, the study aimed to characterize a 'probable' versus 'no or possible' nociplastic pain mechanism using biopsychosocial variables and compare both groups in their one-year post-TKA response. METHODS: A secondary analysis of baseline data of a longitudinal prospective study involving 197 KOA patients awaiting total knee arthroplasty in Belgium and the Netherlands was performed. Two approaches, one considering four and the other three pain locations (step 2 of the grading system), were presented. Linear mixed model analyses were performed to compare the 'probable' and 'no or possible' nociplastic pain mechanism groups for several preoperative biopsychosocial-related variables and one-year postoperative pain. Also, a sensitivity analysis, comparing exclusively 'probable' versus 'no' nociplastic pain mechanism groups, was performed. RESULTS: Thirty (15.22% - approach four pain locations) and 46 (23.35% - approach three pain locations) participants were categorized under 'probable' nociplastic pain. Irrespective of the pain location approach or sensitivity analysis, the 'probable' nociplastic pain group included more woman, were younger, exhibited worse results on various preoperative pain-related and psychological variables, and had more pain one-year post-TKA compared to the other group. DISCUSSION: This study proposed additional criteria to finetune the grading system for nociplastic pain (except for discrete/regional/multifocal/widespread pain) and characterized a subgroup of KOA patients with 'probable' nociplastic pain. Future research is warranted for further validation.

Concurrent validity of dynamic bedside quantitative sensory testing paradigms in breast cancer survivors with persistent pain.

BACKGROUND: Studies on the concurrent validity of clinically applicable testing protocols for conditioned pain modulation (CPM) and temporal summation of pain (TSP) in breast cancer survivors (BCS) with persistent pain are lacking. OBJECTIVES: This study investigated the concurrent validity of two bedside protocols for CPM and TSP in comparison to a respective reference protocol. The participants' preferences for bedside CPM and TSP protocols were assessed. METHODS: Thirty BCS experiencing persistent pain were included in this study. Each participant underwent a reference test along with two bedside alternatives for assessing both TSP and CPM. For CPM, a cold pressor test (CPT) and blood pressure cuff (BPC) were used as conditioning stimulus. The test stimulus was elicited in parallel by pressure pain threshold after 45 and 90 s of conditioning at the lower limb. The CPM reference test consisted of parallel heat stimuli at the forearms using a two-thermode system. TSP was elicited using a von Frey monofilament (256 mN) and an algometer (98 kPa) at the affected site and opposite lower limb. The TSP reference test consisted of heat stimuli at the affected site and opposite lower limb. Participants' testing preference was examined using a purpose-designed questionnaire. Spearman's rank test examined the correlation between protocols. RESULTS: The two bedside CPM protocols were strongly correlated (r = 0.787-0.939, p < 0.005). A strong correlation was found between the BPC protocol and reference test using the relative effect magnitude (r = 0.541-0.555, p < 0.005). The bedside TSP protocols were moderately correlated with each other only at the lower limb using absolute change scores (r = 0.455, p = 0.012). No significant correlation was found between the bedside and reference TSP protocols. CONCLUSION: The significantly moderate to very strong correlations between the bedside protocols validate their interchangeability. Researchers and clinicians should be able to choose which bedside protocol they utilize; however, participants favored the use of a BPC and algometer for the evaluation of CPM and TSP, respectively.

Reliability and construct validity of the ACTIVLIM-Hemo and Haemophilia Activities List (HAL) questionnaires in individuals with haemophilia.

OBJECTIVE: The objective of this study is to assess the reliability and construct validity of ACTIVLIM-Hemo, a newly developed Rasch-built questionnaire designed to evaluate activity limitations in people with haemophilia (PwH), in comparison with the Haemophilia Activities List (HAL), which was developed using Classical Test Theory. METHODS: A total of 130 participants with haemophilia A or B were included. They underwent various assessments, including joint health scoring (HJHS), functional tests (TUG and 2MWT) and completed questionnaires such as the BPI, IPAQ, HAL and ACTIVLIM-Hemo. Reliability indices and the minimum detectable change (MDC95) were determined for ACTIVLIM-Hemo and for HAL. Construct validity was evaluated through correlations and multiple linear regression, considering demographic and clinical factors. RESULTS: Both ACTIVLIM-Hemo (Person Separation Index = 0.92) and HAL (Cronbach's α = 0.98) demonstrated high reliability. The MDC95 for ACTIVLIM-Hemo represented 11.6% of its measurement range, while for HAL, it amounted to 18/100 score points. Activity limitations measured by both instruments were significantly correlated with demographic and clinical factors. Joint health (HJHS), pain severity (BPI) and walking performance (2MWT) emerged as the main predictors of activity limitations, explaining 75% of the variance in ACTIVLIM-Hemo and 60% in HAL. CONCLUSION: ACTIVLIM-Hemo stands as a reliable and valid instrument for assessing activity limitations in PwH. Both instruments exhibited significant correlations with demographic and clinical factors, but ACTIVLIM-Hemo displayed a more homogeneous construct. Given its linear scale and lower MDC95 and better targeting, ACTIVLIM-Hemo shows promise as a patient-centric instrument for assessing responsiveness to treatment during individual follow-up.

Joint status, pain and quality of life in elderly people with haemophilia: A case-control study.

INTRODUCTION: Elderly people with haemophilia (PwH) develop haemophilic arthropathy, pain, and reduced health-related quality of life (HR-QoL). The condition of elderly mild haemophilia patients have rarely been evaluated. This study aimed to compare joint status, pain, and HR-QoL between elderly with mild, moderate/severe haemophilia and healthy elderlies. METHODS: Knee/ankle abnormalities were assessed by ultrasound (HEAD-US) and physical examination (HJHS 2.1). Pain severity and pain interference were investigated using the Brief Pain Inventory. Pressure pain thresholds (PPTs) were obtained at knees/ankles and forehead. Functional limitations were evaluated using the 2-Minute-Walking-Test, Timed-Up-and-Go and HAL. The EQ-5D-5L questionnaire evaluated HR-QoL. Healthy controls (HCs) and elderly individuals with moderate/severe and mild haemophilia were compared using Kruskal-Wallis and Mann-Whitney U tests. RESULTS: From the 46 elderly PwH approached, 40 individuals (≥60 years) with haemophilia A/B (17 moderate/severe; 23 mild) and 20 age-matched HCs were recruited. Moderate/severe PwH displayed worse joint status, lower PPTs, and poorer HR-QoL than mild PwH and HCs (p-value = .010-<.001). HEAD-US abnormalities were observed in 100% of knees and 94% of ankles in moderate/severe PwH, versus 50% of knees and 61% of ankles in mild PwH. Pain was reported by 80% and 57% of moderate/severe and mild PwH, respectively. Low PPTs, functional limitations, and poor HR-QoL scores were likewise observed in some mild PwH, yet without significantly differing from HCs. CONCLUSION: This study highlights poor joint/functional status, pain, and HR-QoL outcomes in elderly with moderate/severe haemophilia. A few mild haemophilia subjects presented joint abnormalities, pain, functional limitations, and poor HR-QoL, without significantly differing from HCs. HIGHLIGHTS: Elderly individuals with mild haemophilia have not yet been extensively studied, whereas moderate/severe haemophilia individuals have proven to suffer from haemophilic arthropathy, pain, and poor health-related quality of life (HR-QoL). Using a case-control design, joint status, pain, and HR-QoL outcomes were examined in elderly haemophilia individuals and compared with those of healthy controls (HCs). Elderly moderate/severe haemophilia individuals exhibited worse joint status, increased joint pain sensitivity, and reduced HR-QoL compared with both mild haemophilia subjects and HCs. A subset of mild haemophilia subjects exhibited poor joint status, pain, and HR-QoL outcomes, without any differences noted when compared with HCs.

The Classification of Suspected Predominant Nociplastic Pain in People with Moderate and Severe Haemophilia: A Secondary Exploratory Study.

In people with haemophilia (PwH), joint pain is a major comorbidity that is often overlooked and under-treated. It is believed that, to ensure the most successful outcome, pain management should be tailored to the predominant pain phenotype (i.e., nociceptive, neuropathic and nociplastic). The 2021 clinical criteria and grading system for nociplastic pain, established by the International Association for the Study of Pain (IASP), emphasize the necessity of early-stage identification and predominant pain type classification. Consistent with findings in other chronic musculoskeletal pain conditions, studies suggest that a subgroup of PwH suffers from nociplastic pain, i.e., pain arising from altered nociception rather than structural damage, but this has not yet been explored in PwH. This study aimed to identify PwH with "unlikely", "possible" and "probable" nociplastic pain and investigate differences in anthropometric, demographic and clinical characteristics and psychological factors between subgroups of PwH and healthy individuals.: The IASP clinical criteria and grading system were used to classify pain types in adult men with moderate or severe haemophilia recruited from two Belgian haemophilia treatment centres. Statistical analyses were applied to study between-subgroup differences. Of 94 PwH, 80 PwH (85%) were classified with "unlikely" and 14 (15%) with "at least possible" nociplastic pain (including 5 PwH (5%) with "possible" and 9 PwH (10%) with "probable" nociplastic pain). PwH in both the "unlikely" and "at least possible" nociplastic pain groups showed significantly higher levels of unhelpful psychological factors compared to healthy individuals. Additionally, age may partially account for the observed differences in body height and psychological factors. Larger sample sizes may be needed to detect more subtle between-group differences. study confirmed the presence of nociplastic pain in haemophilia, categorising a notable subgroup as individuals who experience at least possible nociplastic pain. These exploratory insights may provide a starting point for future studies and the development of more effective and tailored pain management.

Psychophysical assessment of pain in adults with moderate and severe haemophilia: A cross-sectional study.

BACKGROUND: Joint pain is the hallmark of haemophilia; therefore it seems clinically rather a musculoskeletal than a bleeding disorder. Although joint pain in people with haemophilia (PwH) is a complex and multidimensional problem, pain assessment remains primarily focused on the structural evaluation of their joints. Whereas, only few data are available on the potential implication of psychophysical and psychological factors. OBJECTIVE: This study aimed to perform a psychophysical pain assessment including quantitative sensory testing (QST) and an evaluation of psychological factors in a large sample of PwH, to get insight into the individuals' pain system. METHODS: Ninety-nine adults (36.9 ± 13.5 years) with moderate/severe haemophilia A/B and 46 healthy controls filled in self-reported pain and psychological questionnaires and underwent a QST evaluation including static and dynamic tests. Static tests focused on the determination of thermal detection and pain thresholds and mechanical pressure pain thresholds. Dynamic tests evaluated pain facilitation and the efficacy of endogenous pain inhibition. Besides comparing PwH and healthy controls, between-subgroup differences were studied in PwH based on their pain distribution. RESULTS: The study revealed increased thermal and mechanical pain sensitivity and the presence of unhelpful psychological factors such as anxiety/depression in PwH. Among the subgroups, especially PwH with widespread pain showed altered somatosensory functioning. Enhanced pain facilitation and impaired efficacy of endogenous pain inhibition in PwH could not be observed. CONCLUSION: Altered somatosensory functioning and unhelpful psychological factors, appear to play an important role in the pathophysiology of pain in PwH, especially in PwH with widespread pain.

Associations between psychological factors, pressure pain thresholds and conditioned pain modulation and disability in (sub)-acute low back pain: a three-month follow-up study.

BACKGROUND: The clinical presentation and pain experience of patients with (sub)-acute low back pain ((S)ALBP) can strongly vary in clinical practice. However, despite growing evidence that psychological factors are associated with disability in chronic pain conditions including low back pain, studies examining the influence of psychological factors, quantitative sensory testing (QST) (i.e. pressure pain thresholds (PPTs)) and conditioned pain modulation (CPM) on future disability are still lacking in (S)ALBP. OBJECTIVE: This prospective cohort study aims to determine associations between baseline psychological factors, PPTs and CPM in (S)ALBP and disability after 3 months. METHODS: Fifty-two patients with (S)ALBP underwent a baseline PPT evaluation in rest and during a CPM protocol. Patients were asked to fill in self-report questionnaires: the Visual Analogue Scale (VAS), the Quebec Back Pain Disability Scale (QBPDS), the Pain Catastrophizing Scale (PCS), the Tampa Scale for Kinesiophobia (TSK) and the Illness Perception Questionnaire - Brief version (IPQ-B). At 3-month follow-up, participants were asked to fill in the QBPDS again. Multiple linear regression analysis was conducted to determine associations between baseline factors and disability at follow-up. RESULTS: Thirty-eight patients participated at follow-up. Because of the multicollinearity issue, the TSK score was selected for analyses and the PCS and IPQ-B score were excluded from the model. No significant associations between baseline factors and disability at follow-up were found. CONCLUSION: Neither baseline psychological factors nor PPTs or CPM in (S)ALBP were significantly associated with disability after 3 months. Our multiple linear regression analysis was likely underpowered to detect significant associations.

Pain interferes with daily activities, emotions and sleep in adults with severe, moderate and mild haemophilia: A national cross-sectional survey.

INTRODUCTION: Pain is a major issue in people with haemophilia (PwH). Few studies comprehensively assessed pain in PwH using a biopsychosocial framework and studies in mild PwH are lacking. AIM: To assess pain prevalence, pain interference and their relationship with health-related quality of life (HR-QoL) in male adults with haemophilia. METHODS: A survey was initiated by the Belgian national member organisation. Pain in the last 24 h, pain severity (BPI-PS) and pain interference (BPI-PI) scores were obtained with the Brief Pain Inventory short-form (BPI). HR-QoL was evaluated with the EQ-5D-3L, giving the health utility index (EQ-HUI). Associations between EQ-HUI, BPI-PS and BPI-PI were analysed using Pearson's correlation test. A multiple regression analysed the relationship between HR-QoL and BPI-PS, with age and haemophilia severity as confounding factors. RESULTS: Within 185 respondents (97, 31 and 57 respectively severe, moderate and mild PwH), 67% (118/177) reported pain. In severe, moderate and mild PwH, respectively 86% (79/92), 71% (22/31) and 32% (17/54) reported pain. Median [IQR] BPI-PS, BPI-PI and EQ-HUI scores were respectively 1.5 [.0; 4.0], 1.6 [.0; 3.6] and .81 [.69; 1.00]. PwH reported pain interference with general activity (56% (99/176)), psychosocial factors such as mood (53% (93/175)), and sleep (51% (90/177)). Moderate correlations were found between EQ-HUI, BPI-PS and BPI-PI. After adjusting for age and haemophilia severity, BPI-PS explained 14% of HR-QoL variance. CONCLUSIONS: Pain is a major issue amongst PwH, including people with mild haemophilia. Pain interferes with activities, emotions, sleep and HR-QoL, arguing for a comprehensive biopsychosocial approach of pain.

Discordance between joint pain and imagery severity in the ankle joint and contributors of lower limb activity limitations in adults with haemophilia: A cross-sectional study.

INTRODUCTION: People with haemophilia (PwH) suffer from knee and ankle joint pain, but the association with structural damage remains underexplored. They report activity limitations but it is unclear which factors contribute to lower limb activity limitations (LL-AL). AIMS: This study aimed (i) to analyse the association between ankle joint pain and structure and (ii) explore the contribution of haemophilia-related, individual and psychological factors to LL-AL in PwH. METHODS: This study included 104 moderate/severe PwH. Ankle pain intensity was assessed with a numeric rating scale and pain sensitivity with algometry (pressure pain threshold (PPTA )). Ankle structure was assessed with MRI (IPSG-MRI) and ultrasound (HEAD-US), joint health with the Haemophilia Joint Health Score (HJHS). The HAL-LOWCOM subscore evaluated LL-AL. A Spearman correlation analysed the correlation between ankle pain and structure. The contribution of haemophilia-related factors (joint health, overall pain (Brief Pain Inventory-Pain Severity (BPI-PS)), functional status (2-Minute-Walking-Distance, Timed Up and Go); individual factors (age, BMI) and psychological factors (fear and avoidance beliefs over physical activity (FABQ-PA) and work (FABQ-Work), anxiety and depression) to LL-AL was explored using a regression analysis. RESULTS: Only low correlations were found between ankle pain intensity and structure (IPSG-MRI, HEAD-US). PPTA was unrelated to structure. Altogether, HJHS, overall pain (BPI-PS), FABQ-Work and age explained 69% of HAL-LOWCOM variance, with 65% explained by the combination of HJHS and BPI-PS. CONCLUSION: No meaningful associations were found between ankle pain and structural damage, suggesting that other factors may contribute to PwH's ankle pain. In contrast, mainly haemophilia-related factors explained LL-AL variance.

ACTIVLIM-Hemo: A new self-reported, unidimensional and linear measure of activity limitations in persons with haemophilia.

INTRODUCTION: To assess activity limitations in people with haemophilia (PwH), the self-reported Haemophilia Activity List (HAL) is widely employed, despite several methodological limitations impacting the interpretation of categorical scores. Modern psychometric approaches avoid these limitations by using a probabilistic model, such as the Rasch model. The ACTIVLIM is a Rasch-built measurement of activity limitations previously validated in several clinical conditions like neuromuscular disorders. AIMS: This study sought to develop the ACTIVLIM-Hemo, meaning an ACTIVLIM scale version specifically adapted to assess daily activity limitations in adult PwH. METHODS: Daily activities were assessed as "impossible," "difficult" or "easy" by 114 PwH (median age of 44 years) with 63 of them reassessed after 12 days. The Rasch Rating Scale model was used to identify activities delineating a unidimensional and linear scale unbiased by demographic and clinical status. Concurrent validity was determined through correlation with the HAL sub-scores and sum score. RESULTS: The ACTIVLIM-Hemo included 22 pertinent activities, with difficulties independent of demographic and clinical conditions, allowing a reliable measure of activity limitations (PSI = .92) expressed on a linear and unidimensional scale in PwH (7%-100 % range, ceiling effect of 1/114) with excellent test-retest reliability (ICC = .978). Spearman rank correlations between ACTIVLIM-Hemo and HAL sub-scores ranged between .623 and .869. CONCLUSIONS: The ACTIVLIM-Hemo is an easy-to-administer, valid and reliable alternative to HAL in assessing activity limitations in PwH. Its invariant scale can be used across conditions and time to compare the functional status of PwH over a wide measurement range.

Pain coping behaviour strategies in people with haemophilia: A systematic literature review.

INTRODUCTION: Despite the fact that joint bleeds (haemarthrosis) frequently occur in people with haemophilia (PwH) with invalidating arthropathies as result, the clinical pain experience has received only limited attention. A sudden increase in pain intensity can be linked to a bleed, but in most cases, no acute bleed is confirmed. Nevertheless, a patient's perception of an acute bleed as cause of the pain might impact the patients' behaviour in response to pain. It is therefore essential to gain more insight into pain coping strategies seen in PwH. AIM: This systematic review aims to identify the range of pain coping behaviour strategies used among PwH and the factors associated with pain coping behaviour. METHODS: This review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-analyses guidelines (PRISMA). PubMed and Web of Science were systematically screened for relevant literature using keyword combinations related to adult PwH, pain and pain coping behaviour strategies. Risk of bias was assessed with the modified Newcastle-Ottowa Scale. RESULTS: Eleven full text articles (nine cross-sectional and two comparative studies) consisting of 1832 PwH met the inclusion criteria. Due to the heterogeneity of the study samples, quality of evaluation instruments and varying risk of bias, it was difficult to draw conclusions regarding the used pain coping behaviour strategies and associated factors. CONCLUSION: Literature on pain coping behaviour strategies and associated factors in PwH is still scarce and describes heterogenous results. Validated haemophilia-specific instruments are warranted to inventory pain coping behaviour in a standardized way.

Gaining more insight into ankle pain in haemophilia: A study exploring pain, structural and functional evaluation of the ankle joint.

INTRODUCTION: Ankle arthropathy is highly prevalent among people with haemophilia (PwH), even with prophylaxis, and leads to pain and disability. Mechanisms and consequences of painful symptoms related to ankle arthropathy have not been extensively studied. METHODS: A consecutive sample of 30 adult PwH was included (60 ankles). Ankle structure was assessed with magnetic resonance imaging (IPSG-MRI) and ultrasound (HEAD-US). The HJHS 2.1 assessed function of ankles and knees. Physical functioning was assessed with the Timed Up and Go test, the 2-Minute Walking Test and activity limitations with the HAL questionnaire. Health-related quality of life was evaluated using the EQ-5D-5L questionnaire. Overall pain severity was examined using the Brief Pain Inventory questionnaire and ankle pain intensity with a visual analogue scale. Pressure pain thresholds with an algometer assessed pain sensitivity. Spearman correlations were used to calculate interrelations between joint structure, function and pain. RESULTS: Twenty-five PwH (83%) reported ≥1 painful joint, with 67% reporting the ankle as most painful joint. MRI-confirmed abnormalities were seen in 76% of talocrural and 55% of subtalar joints. HEAD-US abnormalities were seen in 93% of the ankles. A large variation was seen in pain sensitivity at the ankle. While moderate to high correlations were observed between ankle structure and HJHS, no meaningful correlations were found between MRI-scores and pain intensity or sensitivity. CONCLUSIONS: Structural joint damage is present in many ankles but is not related to pain in PwH. Further studies should consider somatosensory nervous system dysfunction in PwH as contributing factor to painful ankle arthropathy.

Pain Neuroscience Education for Children with Functional Abdominal Pain Disorders: A Randomized Comparative Pilot Study.

This article explores the effectiveness of a newly developed Pain Neuroscience Education program for children (PNE4Kids) with functional abdominal pain disorder (FAPD). Children (6-12 years) with FAPD were randomly assigned to 1) the experimental group (n = 14), participating in one hypnotherapy session (i.e., usual care) and one additional PNE4Kids session, or 2) the control group (n = 14), participating in two hypnotherapy sessions. Parental pain catastrophizing, the child's functional disability (parental-proxy), pain-related fear (parent-proxy) and pain intensity, were assessed at baseline and one and three weeks after each therapy session. Pressure algometry and a conditioned pain modulation paradigm were performed at baseline and three weeks after completion of the last therapy session. Parents from both the experimental as well as the control group showed significantly less parental pain catastrophizing (p < 0.01). Children showed significantly less functional disability (p < 0.05), pain-related fear (p < 0.01) and local pressure pain sensitivity (p < 0.05) at short-term follow-up (three weeks after last intervention) in both groups. No significant (p > 0.05) between-group differences were found. Hypnotherapy combined with PNE4Kids did not result in better clinical outcomes compared to hypnotherapy alone. Study limitations include the application of one single PNE4Kids session and the short follow-up time.

Hyperexcitability of the Central Nervous System in Children with Chronic Pain: A Systematic Review.

Objective: Hyperexcitability of the central nervous system plays an important role in the development and maintenance of chronic pain in adults. This knowledge has led to improved treatment strategies within this population. In children, however, research on the presence of central hyperexcitability is scarce. To further investigate this topic in children with chronic pain, there is a need for a clear literature overview. Design: Systematic review. Methods: The literature search was performed using the electronic databases PubMed and Web of Science. An article was considered eligible if it included children (age two to 12 years) diagnosed with chronic pain. Articles had to report original research outcomes related to central hyperexcitability, and a comparison with a healthy control group was necessary. Characteristics of the study sample, the assessment, and conclusions regarding central hyperexcitability were extracted from each included article. Results: Twelve case-control studies were included with moderate to good methodological quality (510 children with chronic pain and 670 healthy controls). After summarizing the articles' results on indices of central hyperexcitability, we concluded that secondary hyperalgesia might be present in children with recurrent abdominal pain, juvenile fibromyalgia, and juvenile idiopathic arthritis. Preliminary evidence exists for altered cortical nociceptive processing in children with migraine and recurrent abdominal pain. Conclusion: Based on the results of this review, central hyperexcitability might be present in in several pediatric chronic pain conditions. Further research on other manifestations of central hyperexcitability (e.g., bottom-up and top-down mechanisms and nociceptive brain changes) is necessary to provide firm evidence about its presence in children with chronic pain.