Emotional Allodynia Questionnaire (AEQ) in Fibromyalgia (PEARL) (PEARL)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain; Fibromyalgia; Nociplastic Pain

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.

• Study Type: Observational
• Enrollment (Estimated): 423

Contacts and Locations

• Study Contact: Name: Alberto Corriero, MD, PhD; Phone Number: +39 3280072443; Email: alberto.corriero@gmail.com

Study Locations

• Italy
  • Bari, Italy, 70124
    • Recruiting
    • Pain Unit, Policlinico di Bari, University of Bari Aldo Moro (coordinating center)
    • Principal Investigator: Mariateresa Giglio, MD
    • Principal Investigator: Filomena Puntillo, MD
    • Principal Investigator: Alberto Corriero, MD, PhD
  • Bologna, Italy, 40138
    • Not yet recruiting
    • Anesthesia and Pain Therapy Unit, IRCCS AOSP di Bologna, Policlinico S. Orsola-Malpighi
    • Principal Investigator: Samolsky Dekel Boaz, MD
  • Cagliari, Italy
    • Not yet recruiting
    • Department of Medical Sciences and Public Health, University of Cagliari
    • Principal Investigator: Gabriele Finco, MD
  • Naples, Italy
    • Not yet recruiting
    • Department of Women, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli
    • Principal Investigator: Maria Caterina Pace, MD
  • Verona, Italy
    • Not yet recruiting
    • Department of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona
    • Principal Investigator: Vittorio Schweiger, MD, PhD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adults attending Italian tertiary pain outpatient services. Cases are identified from fibromyalgia services; controls are identified among patients attending the same services for chronic non-cancer pain of defined nociceptive or neuropathic origin. Consecutive eligible patients are considered for enrollment.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Fibromyalgia cases; Adults with fibromyalgia diagnosed per the 2016 ACR criteria.
Non-fibromyalgia chronic pain controls; Adults with chronic non-cancer pain of defined nociceptive or neuropathic origin who do not meet the 2016 ACR criteria for fibromyalgia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Internal consistency of the Emotional Allodynia Questionnaire (AEQ) in fibromyalgia cases	Internal consistency reliability of the AEQ, an 11-item self-report questionnaire (total score range 0-44), in fibromyalgia cases, assessed using Cronbach's alpha and McDonald's omega, each reported with 95% confidence intervals.	Baseline (T0)
Factorial structure of the Emotional Allodynia Questionnaire (AEQ)	Latent factor structure of the 11-item AEQ self-report questionnaire, assessed by exploratory factor analysis and a single-factor confirmatory factor analysis (CFA). Reported as CFA model fit indices: comparative fit index (CFI), Tucker-Lewis index (TLI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR).	Baseline (T0)
Known-groups discriminative accuracy of the AEQ (AUC)	Discriminative accuracy of the AEQ total score (11-item self-report questionnaire) in distinguishing fibromyalgia cases from non-fibromyalgia chronic pain controls, reported as the area under the receiver operating characteristic (ROC) curve (AUC, range 0-1) with 95% confidence interval, tested against a null value of 0.70.	Baseline (T0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Convergent validity of the Emotional Allodynia Questionnaire (AEQ)	Convergent validity reported as Spearman rank correlation coefficients (rho, range -1 to 1) between the AEQ total score and the Central Sensitization Inventory (CSI), Pain Catastrophizing Scale (PCS), Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI-Y), and Difficulties in Emotion Regulation Scale (DERS).	Baseline (T0)
Discriminant validity of the Emotional Allodynia Questionnaire (AEQ) versus the DERS	Discriminant validity of the AEQ relative to the DERS, reported as (a) a chi-square statistic for dissociation across AEQ and DERS median-split groups and (b) the Fornell-Larcker criterion, comparing the AEQ's average variance extracted (AVE) with the squared AEQ-DERS correlation (proportions, range 0-1).	Baseline (T0)
Test-retest reliability of the Emotional Allodynia Questionnaire (AEQ) total score	Test-retest reliability of the AEQ total score (11-item self-report questionnaire) in the full enrolled sample (cases and controls), reported as the intraclass correlation coefficient (ICC, range 0-1; two-way mixed-effects model, absolute agreement, single rater) with 95% confidence interval.	Baseline (T0) and retest at approximately 40 days (plus or minus 10 days)
AEQ score distribution across AEQ-CSI median-split phenotypes	Distribution of the AEQ total score (points, range 0-44) across the four AEQ-CSI median-split phenotypes (Resilient, Emotional Allodynia, Central Sensitization, Mixed), and between-phenotype differences on validated measures not used to define them (PCS, BDI-II, STAI-Y, DERS total scores)	Baseline (T0)
Floor and ceiling effects of the Emotional Allodynia Questionnaire (AEQ)	Reported as the percentage of participants (%) scoring at the minimum (floor) and at the maximum (ceiling) of the AEQ total score (11-item self-report questionnaire, total score range 0-44).	Baseline (T0)
Depression-stratified internal consistency and convergent validity of the AEQ	Computed separately within fibromyalgia cases stratified by presence vs. absence of major depressive disorder, reported as Cronbach's alpha (range 0-1) and Spearman correlation coefficients (rho, range -1 to 1) of the AEQ total score with CSI, PCS, BDI-II, STAI-Y, and DERS.	Baseline (T0)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concordance between AEQ-CSI phenotypes and data-driven clusters	Agreement between the theory-driven AEQ-CSI median-split phenotypes (Resilient, Emotional Allodynia, Central Sensitization, Mixed) and data-driven clusters from k-means, hierarchical clustering (Ward's method), and latent class analysis (LCA), reported as the Adjusted Rand Index (range -1 to 1).	Baseline (T0)

Collaborators and Investigators

• Sponsor: University of Bari
• Collaborators: IRCCS Azienda Ospedaliero-Universitaria di Bologna; Universita di Verona; University of Cagliari; University of Campania Luigi Vanvitelli
• Investigators: Principal Investigator: Alberto Corriero, MD, PhD, University of Bari Aldo Moro, Pain and ICU Section

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: June 20, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Fibromyalgia; Emotion regulation; Psychometric validation; Central sensitization; Nociplastic pain; Emotional Allodynia Questionnaire
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Rheumatic Diseases; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Social Behavior; Self-Control; Fibromyalgia; Chronic Pain; Emotional Regulation; Nociplastic Pain
• Other Study ID Numbers: PEARL-MC-2026; 2451/CEL (Other Identifier: Ethics Committee protocol number (preliminary single-center phase))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared publicly. Under Italian data protection regulations and the EU General Data Protection Regulation (GDPR), participant-level data from this study cannot be made publicly available. The working dataset is pseudonymized and held on secure institutional systems. De-identified data supporting the main findings may be made available from the corresponding author upon reasonable request, subject to a data-sharing agreement and compliance with applicable data-protection requirements.

Drug and device information, study documents

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