Emotional Allodynia Questionnaire (AEQ) in Fibromyalgia (PEARL)

Design: multicenter (Italian tertiary pain centers), observational, case-control psychometric validation study. Cases are adults with fibromyalgia (2016 ACR criteria); controls are adults with chronic non-cancer pain of defined nociceptive or neuropathic origin who do not meet fibromyalgia criteria. Group membership reflects clinical diagnosis and is not assigned by the investigators.

Assessment: the primary assessment is cross-sectional at baseline (T0). All enrolled participants (cases and controls) are reassessed once for test-retest reliability (T1) at approximately 40 days (plus or minus 10 days). The battery comprises the AEQ, Central Sensitization Inventory (CSI), Pain Catastrophizing Scale (PCS), Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI-Y forms 1 and 2), Difficulties in Emotion Regulation Scale (DERS), and a Visual Analog Scale (VAS) for pain. Questionnaires are self-administered on paper with physician-verified completeness at the point of care, then transcribed into a secure online data-collection form.

Sample size: two targets. The fibromyalgia cohort comprises 274 patients (137 per depression stratum, sized for internal consistency and depression-stratified estimation; PASS 2024 v24.0.5). For the known-groups discriminative analysis, 151 evaluable non-fibromyalgia chronic pain controls are required, sized on precision for a 95% confidence interval of width 0.10 around an anticipated AUC of 0.80 (Hanley-McNeil standard-error method, PASS 2024 v24.0.9); the 97-per-group level is the minimum to test an AUC of 0.80 against a null of 0.70 (two-sided alpha 0.05, 80% power; Hanley-McNeil / Obuchowski-McClish).

Primary analysis: ROC analysis with the AEQ total score as classifier and diagnostic group as the reference (fibromyalgia = positive); the AUC is tested against 0.70 with its 95% CI. A covariate-adjusted logistic-regression sensitivity analysis (age, sex, depressive comorbidity) and a center-adjusted analysis are pre-specified. Secondary analyses include convergent and discriminant validity, exploratory and confirmatory factor analysis, test-retest ICC, AEQ-CSI median-split phenotyping (Resilient, Emotional Allodynia, Central Sensitization, Mixed), a pre-specified depression-stratified analysis, and exploratory unsupervised clustering.

CASES (fibromyalgia)

Inclusion criteria

• Age 18 years or older
• Clinical diagnosis of fibromyalgia confirmed according to the 2016 revision of the ACR criteria
• Chronic non-cancer pain for at least 3 months
• Ability to understand and independently complete self-report questionnaires in Italian
• Willingness to provide written informed consent

Exclusion criteria

• Active oncological disease or cancer-related pain
• Any current or past psychiatric diagnosis except Major Depressive Disorder and Panic Disorder (assessed by clinical history)
• Severe cognitive impairment precluding questionnaire completion
• Inability to understand or complete questionnaires in Italian

CONTROLS (non-fibromyalgia chronic pain)

Inclusion criteria

• Age 18 years or older
• Chronic non-cancer pain for at least 3 months with a defined nociceptive or neuropathic generator (e.g., radiologically or surgically documented degenerative, structural, or post-surgical musculoskeletal pain, or neuropathic pain with an identifiable neurological lesion or disease)
• Not meeting the 2016 ACR criteria for fibromyalgia
• Ability to understand and independently complete self-report questionnaires in Italian
• Willingness to provide written informed consent

Exclusion criteria

(parallel to cases):

• Diagnosis of fibromyalgia or another recognized nociplastic primary pain condition (e.g., primary chronic widespread pain)
• Active oncological disease or cancer-related pain
• Any current or past psychiatric diagnosis except Major Depressive Disorder and Panic Disorder
• Severe cognitive impairment precluding questionnaire completion
• Inability to understand or complete questionnaires in Italian

Note: ongoing pharmacological treatment for pain or mental health is not an exclusion criterion in either group; Major Depressive Disorder and Panic Disorder are recorded at baseline and used in covariate-adjusted and stratified analyses.