Chronic Pain, Fibromyalgia, Nociplastic Pain
Conditions
Keywords
Emotional Allodynia Questionnaire, Fibromyalgia, Nociplastic pain, Psychometric validation, Central sensitization, Emotion regulation
Brief summary
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. Protocol amendment (version 2.1, 5 September 2026). The statistical analysis plan is revised as follows: (1) latent profile analysis on the continuous scores replaces latent class analysis as the primary model-based method for unsupervised phenotyping; (2) discriminant validity by the Fornell-Larcker criterion is examined against the Pain Catastrophizing Scale in addition to the DERS; (3) the AUC is additionally reported, descriptively, within the nociceptive and neuropathic subgroups of the control cohort. Eligibility, procedures, participant burden and consent are unchanged.
Interventions
None listed
Sponsors
University of Bari
Universita di Verona
University of Campania Luigi Vanvitelli
University of Cagliari
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Internal consistency of the Emotional Allodynia Questionnaire (AEQ) in fibromyalgia cases | Baseline (T0) | 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. |
| Factorial structure of the Emotional Allodynia Questionnaire (AEQ) | Baseline (T0) | 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). |
| Known-groups discriminative accuracy of the AEQ (AUC) | Baseline (T0) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Convergent validity of the Emotional Allodynia Questionnaire (AEQ) | Baseline (T0) | 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). |
| Discriminant validity of the Emotional Allodynia Questionnaire (AEQ) versus the DERS | Baseline (T0) | 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). |
| Test-retest reliability of the Emotional Allodynia Questionnaire (AEQ) total score | Baseline (T0) and retest at approximately 40 days (plus or minus 10 days) | 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. |
| AEQ score distribution across AEQ-CSI median-split phenotypes | Baseline (T0) | 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) |
| Floor and ceiling effects of the Emotional Allodynia Questionnaire (AEQ) | Baseline (T0) | 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). |
| Depression-stratified internal consistency and convergent validity of the AEQ | Baseline (T0) | 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. |
Countries
Italy
Contacts
CONTACTAlberto Corriero, MD, PhD
PRINCIPAL_INVESTIGATORAlberto Corriero, MD, PhD
University of Bari Aldo Moro, Pain and ICU Section
Outcome results
None listed