Central Pain Mechanisms and Clinical and Psychological Factors Associated With Pain Interference in Daily Life in Adults With Hemophilia and Hemophilic Arthropathy

Central Pain Mechanisms and Clinical and Psychological Factors Associated With Pain Interference in Daily Life in Adults With Hemophilia and Hemophilic Arthropathy: A Cross-Sectional Observational Study

Introduction. Chronic pain is a frequent complication in adults with hemophilia and hemophilic arthropathy that affects functionality and quality of life. In addition to joint damage, central pain mechanisms and psychological factors may contribute to its functional impact, although evidence in this population is limited.

Objective. To analyze the association between central pain mechanisms, pain intensity, and pain-related anxiety and pain interference in daily life in adults with hemophilia and hemophilic arthropathy, adjusting for relevant clinical variables.

Methods. An analytical observational study with a cross-sectional design will be conducted in 138 adults with hemophilia and hemophilic arthropathy. The dependent variable will be pain interference in daily life (Brief Pain Inventory), the main predictor variables will be central sensitization (Central Sensitization Inventory), conditioned pain modulation (Conditioned Pain Modulation Index), global pain intensity (severity subscale of the Brief Pain Inventory), and pain-related anxiety (Pain Anxiety Symptoms Scale-20). As secondary predictor variables, sleep quality (Pittsburgh Sleep Quality Index) and pain self-efficacy (Pain Self-Efficacy Questionnaire) will be included. As confounding variables, joint damage, age, type of treatment, and history of inhibitor will be considered. The association between variables will be analyzed using multiple linear regression models adjusted for relevant clinical covariates.

Expected results. It is expected to identify factors associated with pain interference in adults with hemophilia and hemophilic arthropathy, improving the understanding of its functional impact.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemophilia

• Study Type: Observational
• Enrollment (Estimated): 138

Contacts and Locations

• Study Contact: Name: Rubén Cuesta-Barriuso, PhD; Phone Number: 0034 985103386; Email: cuestaruben@uniovi.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with hemophilia

Description

Inclusion Criteria:

• Diagnosis of hemophilia A or B
• Age equal to or greater than 35 years
• Clinical diagnosis of hemophilic arthropathy in at least one lower limb joint
• Clinically relevant joint involvement, defined as a total score on the Hemophilia Joint Health Score (HJHS) greater than 4 points
• Stable prophylactic treatment with FVIII/FIX concentrates or monoclonal antibodies
• Provision of written informed consent

Exclusion Criteria:

• Presence of neurological or cognitive impairments that prevent understanding of the questionnaires or performance of the study tests
• Episode of hemarthrosis in the lower limbs within the 3 months prior to assessment
• Use of analgesics, nonsteroidal anti-inflammatory drugs, opioids, or other medications with potential effects on pain perception or modulation within the 72 hours prior to assessment
• Receiving, at the time of the study, physiotherapy, infiltrative, or orthotic interventions aimed at pain or function of joints affected by hemophilic arthropathy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Observational group; adults with hemophilia and hemophilic arthropathy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of pain interference in daily life and global pain intensity at baseline.	The Brief Pain Inventory (BPI-Interference) will be used to assess pain interference in daily life and global pain intensity. This instrument measures the extent to which pain interferes with basic and relevant activities such as general activity, walking, normal work, mood, sleep, social relations, and enjoyment of life. It does not assess pain mechanisms, but rather their perceived functional impact. It consists of 7 items scored from 0 to 10 (0: does not interfere; 10: completely interferes), and the total score is obtained by calculating the mean of the items.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of central sensitisation at baseline.	The Spanish version of the Central Sensitization Inventory will be used to assess the presence of central sensitisation in patients. This inventory includes a first part with 25 items that assess symptoms associated with central sensitisation. Each item is evaluated using a 5-point Likert scale with a numerical hierarchy: Never (0), Rarely (1), Sometimes (2), Often (3), and Always (4). The second part assesses whether the patient has any diagnosis among a list of 10 disorders, including the year of diagnosis. The score of the first part ranges from 0 to 100 points, where higher scores indicate greater clinical severity.	Baseline
Assessment of conditioned pain modulation at baseline.	The Conditioned Pain Modulation Index (CPMI) will be used to assess endogenous pain inhibitory function. Pressure pain threshold (PPT) will be measured at the dorsal aspect of the distal phalanx of the thumb before and during a conditioned stimulus induced by an ischemic test in the contralateral upper limb (sphygmomanometer inflated to 240 mmHg). Patients will report pain intensity on a numerical rating scale (0-10) until reaching 7/10, supported by wrist extension exercises if needed. PPT will be reassessed during the conditioned stimulus. The cuff will remain inflated for up to 6 minutes.	Baseline
Assessment of pain-related anxiety at baseline.	The Pain Anxiety Symptoms Scale-20 (PASS-20) will be used to assess levels of pain-related anxiety. This scale includes 20 items and measures anxiety and fear responses associated with the experience of chronic or recurrent pain. Each item is scored on a scale from 0 to 5, where 0 indicates "never" and 5 indicates "always". It evaluates different dimensions of pain-related anxiety, including cognitive, physiological, and behavioural responses associated with pain experience.	Baseline
Assessment of sleep quality at baseline.	Sleep quality will be assessed using the Pittsburgh Sleep Quality Index. The original version consists of 19 items. The first four items have an open-ended response format and assess sleep duration. The remaining items are related to sleep disturbances and daytime dysfunction. Using a 4-point Likert scale, the frequency of each situation is indicated (0: not during the last month; 1: less than once per week; 2: once or twice per week; 3: three or more times per week) and overall sleep quality is rated (0: very good; 1: fairly good; 2: fairly bad; 3: very bad). Scores are distributed across different components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each component ranges from 0 to 3, with a global score ranging from 0 to 21. Higher scores indicate greater disturbance in the evaluated sleep components. A global score greater than	Baseline
Assessment of pain self-efficacy at baseline.	The Pain Self-Efficacy Questionnaire (PSEQ) will be used as a self-report tool to assess the degree of perceived self-efficacy of patients in relation to pain, that is, the confidence of an individual to perform functional and daily life activities in the presence of chronic pain. It is used in individuals with chronic musculoskeletal pain. It consists of 10 items related to activities such as household tasks, work, social activities, and coping with pain, regardless of perceived pain intensity. Each item is measured on a 7-point Likert scale (0: not at all confident; 6: completely confident), with a maximum score of 60 points. Higher scores indicate greater pain self-efficacy.	Baseline
Assessment of joint damage at baseline.	The Hemophilia Joint Health Score (HJHS) will be used to assess joint damage. It is a scale designed to identify joint degeneration in elbows, knees, and ankles in children, adolescents, and adults with hemophilia. It consists of 8 items: swelling and its duration, pain, muscle atrophy and strength, crepitus, and loss of flexion and extension. Scores range from 0 to 20 points (maximum joint damage) per joint. For total joint damage assessment, a gait evaluation is added (range 0-4 points), with a maximum total score of 124 points.	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the sociodemographic variable age at baseline	The sociodemographic variable age will be measured in months completed from the patient's date of birth to the date of the assessment.	Baseline
Assessment of the clinical variable development of inhibitors at baseline	The clinical variable development of inhibitors to clotting factor concentrates will be measured using a dichotomous qualitative variable with two response options: yes/no.	Baseline
Assessment of the clinical variable type of treatment at baseline	The clinical variable type of treatment will be measured using a dichotomous qualitative variable with two response options: on deman / prophylaxis	Baseline

Collaborators and Investigators

• Sponsor: Investigación en Hemofilia y Fisioterapia

Study record dates

Study Major Dates

• Study Start (Estimated): April 22, 2026
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): July 11, 2026

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Anxiety; Chronic pain; Self-efficacy; Pain measurement; Hemophilia; Pain perception
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Mental Disorders; Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Anxiety Disorders; Chronic Pain; Hemophilia A
• Other Study ID Numbers: HE-DOLIFE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No