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

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.

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.

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.

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

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.

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.