Emotional Allodynia Questionnaire (AEQ) in Fibromyalgia (PEARL)

Official title

Pain, Emotional Allodynia, and Relational Load (PEARL): A Multicenter Validation Study of the Emotional Allodynia Questionnaire in Fibromyalgia

Overview

The Emotional Allodynia Questionnaire (AEQ) is an 11-item self-report instrument that measures disproportionate emotional reactivity to low-intensity interpersonal cues(perceived unresponsiveness, exclusion, loss of reciprocity), a pattern termed emotional allodynia. It was preliminarily validated in a single-center fibromyalgia sample. PEARL (validation phase) is a multicenter, prospective, observational psychometric validation study that (1) replicates the internal structure and convergent validity of the AEQ in an independent fibromyalgia sample, (2) tests its known-groups (discriminative) accuracy in separating fibromyalgia from non-fibromyalgia chronic pain of defined nociceptive or neuropathic origin, expressed as the area under the ROC curve (AUC), and (3) assesses test-retest reliability. There is no intervention.

Detailed description

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.

Primary outcome measures

• Internal consistency of the Emotional Allodynia Questionnaire (AEQ) in fibromyalgia cases [Time frame: Baseline (T0)]
• Factorial structure of the Emotional Allodynia Questionnaire (AEQ) [Time frame: Baseline (T0)]
• Known-groups discriminative accuracy of the AEQ (AUC) [Time frame: Baseline (T0)]

Secondary outcome measures (6)

• Convergent validity of the Emotional Allodynia Questionnaire (AEQ) [Time frame: Baseline (T0)]
• Discriminant validity of the Emotional Allodynia Questionnaire (AEQ) versus the DERS [Time frame: Baseline (T0)]
• Test-retest reliability of the Emotional Allodynia Questionnaire (AEQ) total score [Time frame: Baseline (T0) and retest at approximately 40 days (plus or minus 10 days)]
• AEQ score distribution across AEQ-CSI median-split phenotypes [Time frame: Baseline (T0)]
• Floor and ceiling effects of the Emotional Allodynia Questionnaire (AEQ) [Time frame: Baseline (T0)]
• Depression-stratified internal consistency and convergent validity of the AEQ [Time frame: Baseline (T0)]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

Italy · 5 centers

• Pain Unit, Policlinico di Bari, University of Bari Aldo Moro (coordinating center) — Bari
• Anesthesia and Pain Therapy Unit, IRCCS AOSP di Bologna, Policlinico S. Orsola-Malpighi — Bologna
• Department of Medical Sciences and Public Health, University of Cagliari — Cagliari
• Department of Women, Child and General and Specialized Surgery, University of Campania Lui — Naples
• Department of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona — Verona

Publications

• Corriero A, Giglio M, Pilolla A, Galdini F, Mucci O, Vurro M, Fornarelli F, Di Venosa C, Trerotoli P, Puntillo F. The Emotional Allodynia Questionnaire: Preliminary Validation and Clinical Phenotyping in Fibromyalgia. J Pain Res. 2026 Jun 3;19:607309. doi: 10.2147/JPR.S607309. eCollection 2026. PMID 42261300

Identifiers

NCT: NCT07677631 · PEARL-MC-2026 · 2451/CEL

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗