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Session-Order Sensitivity of TS and OA in a Capsaicin Crossover Model (TS-OA-Cap)

3 juin 2026 mis à jour par: John Srbely, University of Guelph

Session-order Sensitivity of Temporal Summation and Offset Analgesia in a Randomised Crossover Capsaicin Model of Secondary Hyperalgesia

Temporal summation (TS) and offset analgesia (OA) are widely used psychophysical endpoints in pain research that index different components of central nociceptive processing. While crossover designs are commonly used in experimental pain studies to reduce between-participant variability, the design-stability of these endpoints under repeated testing during experimental sensitisation is not well characterised. This study compared the design-stability of mechanical TS (Sumscore) and offset analgesia magnitude (OffA) in a two-period, vehicle-controlled crossover trial of capsaicin-evoked secondary hyperalgesia in healthy adults. The primary aim was methodological: to determine whether session-order effects differ between TS and OffA when these are used as outcome measures in two-period crossover designs of capsaicin-induced central sensitisation. Topical capsaicin was used as a reversible experimental intervention to create a controlled, transient state of secondary hyperalgesia rather than as a therapeutic intervention. The study informs endpoint selection in future quantitative sensory testing (QST) crossover trials.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

This was a single-site, two-period, vehicle-controlled, allocation- and formulation-blinded, randomised crossover study conducted at the Department of Human Health Science, University of Guelph, Canada. Sixteen healthy adult volunteers (10 female, 6 male; mean age 21.9 years) were recruited between May 2024 and April 2025. Participants were randomised in a 1:1 intended allocation to one of two sequences: capsaicin-first then vehicle (Sequence A-to-B) or vehicle-first then capsaicin (Sequence B-to-A); actual allocation was 6:10. The allocation sequence was computer-generated by a research assistant not involved in outcome collection. Sessions were separated by a minimum 1-week washout. Topical 0.075% capsaicin cream (Zostrix; Hi-Tech Pharmacal) was applied as a 5 mL dose to a 5 x 10 cm target area on the lateral elbow and to bilateral C5-C6 cervicothoracic dermatomes. The comparator was an equivalent 5 mL volume of inert vehicle lotion (Lubriderm; Johnson & Johnson) applied identically; creams were matched for colour and texture and prepared by a research assistant in unlabelled containers. Mechanical temporal summation (Sumscore; 256 mN pinprick, 16 stimuli at 1 Hz) and thermal offset analgesia (OA; 32-46°C stepped-stimulus protocol with three thermal hold durations of 5, 10, and 15 s) were assessed at baseline and at 10, 20, 30, and 40 min post-intervention. Continuous pain ratings during thermal stimulation were captured via CoVAS. Primary outcomes (Sumscore and the duration-averaged baseline-normalised OffA) were analysed using REML linear mixed-effects models with fixed effects for Intervention, Time, Intervention x Time, Period, and Sequence, with random intercepts for Participant; sex was included as a pre-specified covariate. Within-session temporal stability was assessed using ICC(2,1). A combined Measure x Intervention x Period model tested for differential design-sensitivity between TS and OffA. The study was approved by the University of Guelph Research Ethics Board (REB #19-06-003).

Type d'étude

Interventionnel

Inscription (Réel)

16

Phase

  • N'est pas applicable

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Canada
    • Ontario
      • Guelph, Ontario, Canada, N1G2W1
        • Human Health Sciences, University of Guelph

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Oui

La description

Inclusion Criteria:

  • Healthy adult volunteers (≥18 years of age)
  • Able to provide written informed consent in English

Exclusion Criteria:

  • Current or chronic pain
  • Neurological disease
  • Skin conditions or sensitivity over the test sites to capsaicin
  • Contraindications to thermal stimulation of the skin
  • Musculoskeletal conditions that could alter somatosensory processing
  • Use of analgesic medications within 24 hours prior to each session
  • Use of caffeine within 24 hours prior to each session
  • Use of alcohol within 24 hours prior to each session

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Science basique
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation croisée
  • Masquage: Tripler

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Arm 1: Sequence A-to-B (Capsaicin first)
Participants received topical 0.075% capsaicin (Zostrix) cream (5 mL) in Period 1, followed by topical inert (Lubriderm) vehicle (5 mL) in Period 2. Periods were separated by a minimum 1-week washout. n = 6.
Médicament: Topical 0.075% capsaicin cream (Zostrix)
5 mL of 0.075% capsaicin cream (Zostrix; Hi-Tech Pharmacal, Amityville, NY, USA) applied to a 5 x 10 cm target region on the lateral elbow and to bilateral C5-C6 cervicothoracic dermatomes (total 15 mL). The cream was massaged into the skin by a gloved investigator until no residue was visible. Used as an experimental probe to evoke transient, reversible secondary hyperalgesia; not under therapeutic evaluation.
Autre: Topical vehicle lotion (Lubriderm)
5 mL of inert vehicle lotion (Lubriderm; Johnson & Johnson, Montgomery, NJ, USA) applied to the same dermatomes as the capsaicin condition (total 15 mL), using the identical preparation and massage technique. Matched to the capsaicin cream for colour and texture.
Comparateur actif: Arm 2: Sequence B-to-A (Vehicle first)
Participants received topical inert (Lubriderm) vehicle (5 mL) in Period 1, followed by topical 0.075% capsaicin (Zostrix) cream (5 mL) in Period 2. Periods were separated by a minimum 1-week washout. n = 10.
Médicament: Topical 0.075% capsaicin cream (Zostrix)
5 mL of 0.075% capsaicin cream (Zostrix; Hi-Tech Pharmacal, Amityville, NY, USA) applied to a 5 x 10 cm target region on the lateral elbow and to bilateral C5-C6 cervicothoracic dermatomes (total 15 mL). The cream was massaged into the skin by a gloved investigator until no residue was visible. Used as an experimental probe to evoke transient, reversible secondary hyperalgesia; not under therapeutic evaluation.
Autre: Topical vehicle lotion (Lubriderm)
5 mL of inert vehicle lotion (Lubriderm; Johnson & Johnson, Montgomery, NJ, USA) applied to the same dermatomes as the capsaicin condition (total 15 mL), using the identical preparation and massage technique. Matched to the capsaicin cream for colour and texture.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Mechanical temporal summation (Sumscore)
Délai: Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
Sumscore is a summed pinprick temporal-summation response computed from a train of 16 repeated 256 mN pinprick stimuli delivered perpendicularly to the skin at 1 Hz, paced by a metronome. Pain ratings (NPRS 0-10) immediately after each stimulus were summed (Clouse et al., 2021). The primary Sumscore endpoint was pre-specified as the average of the lateral and inferior testing sites at the lateral elbow, expressed as a baseline-normalised ratio.
Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
Offset analgesia magnitude (OffA)
Délai: Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
OffA was measured during a three-phase stepped-stimulus thermal protocol (32-45-46-45-32°C; T1/T2/T3 phases) using a 32 x 32 mm Peltier contact thermode (TSA-II NeuroSensory Analyzer, Medoc AMS). Continuous pain ratings were collected via CoVAS (0-100) at 10 Hz. OA magnitude was quantified as peak minus nadir CoVAS during the 46°C hold and the subsequent 45°C phase. The primary OffA endpoint was pre-specified as the duration-averaged value across three thermal hold durations (5, 10, and 15 s at 46°C), expressed as a baseline-normalised ratio.
Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Within-session temporal stability (ICC(2,1)) of Sumscore and OffA
Délai: 10, 20, 30, and 40 minutes post-intervention
Intraclass correlation coefficient (ICC(2,1); Shrout and Fleiss, 1979) computed across the four post-intervention time points (10, 20, 30, 40 min) within each intervention condition, separately for Sumscore and OffA. Reported with bias-corrected bootstrap 95% confidence intervals.
10, 20, 30, and 40 minutes post-intervention
Differential design-sensitivity (Measure × Intervention × Period interaction)
Délai: 10, 20, 30, and 40 minutes post-intervention, across two crossover periods separated by a minimum 1-week washout.
A combined linear mixed-effects model using within-measure z-scored outcomes tested whether the period-adjusted intervention estimate differed between TS and OffA. Three-way Measure x Intervention x Period interaction tested via Wald F-tests with residual degrees of freedom.
10, 20, 30, and 40 minutes post-intervention, across two crossover periods separated by a minimum 1-week washout.

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

University of Guelph

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

1 mai 2024

Achèvement primaire (Réel)

30 avril 2025

Achèvement de l'étude (Réel)

30 avril 2025

Dates d'inscription aux études

Première soumission

22 mai 2026

Première soumission répondant aux critères de contrôle qualité

3 juin 2026

Première publication (Réel)

4 juin 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

4 juin 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

3 juin 2026

Dernière vérification

1 juin 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • GUELPH-REB-19-06-003
  • REB #19-06-003 (Autre identifiant: University of Guelph)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

De-identified individual participant data (IPD) and statistical analysis code will be available from the corresponding author on reasonable request, subject to a data-use agreement and institutional ethics/data-sharing requirements. Materials required to reproduce the intervention and assessment protocol are described in the published Methods and Supplementary Materials.

Délai de partage IPD

On request following publication of the primary manuscript.

Critères d'accès au partage IPD

Reasonable request to the corresponding author for non-commercial research use, subject to a data-use agreement consistent with University of Guelph data-sharing policy.

Type d'informations de prise en charge du partage d'IPD

  • PROTOCOLE D'ÉTUDE
  • SÈVE
  • CIF
  • ANALYTIC_CODE

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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