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

2026年6月3日 更新者：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.

調査の概要

状態

完了

条件

介入・治療

詳細な説明

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).

研究の種類

介入

入学 (実際)

16

段階

  • 適用できない

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • カナダ
    • Ontario
      • Guelph、Ontario、カナダ、N1G2W1
        • Human Health Sciences, University of Guelph

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

はい

説明

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

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：基礎科学
  • 割り当て：ランダム化
  • 介入モデル：クロスオーバー割り当て
  • マスキング：トリプル

武器と介入

参加者グループ / アーム
介入・治療
実験的：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.
薬：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.
他の：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.
アクティブコンパレータ：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.
薬：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.
他の：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.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Mechanical temporal summation (Sumscore)
時間枠：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)
時間枠：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)

二次結果の測定

結果測定
メジャーの説明
時間枠
Within-session temporal stability (ICC(2,1)) of Sumscore and OffA
時間枠：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)
時間枠：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.

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

University of Guelph

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2024年5月1日

一次修了 (実際)

2025年4月30日

研究の完了 (実際)

2025年4月30日

試験登録日

最初に提出

2026年5月22日

QC基準を満たした最初の提出物

2026年6月3日

最初の投稿 (実際)

2026年6月4日

学習記録の更新

投稿された最後の更新 (実際)

2026年6月4日

QC基準を満たした最後の更新が送信されました

2026年6月3日

最終確認日

2026年6月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • GUELPH-REB-19-06-003
  • REB #19-06-003 (その他の識別子：University of Guelph)

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

はい

IPD プランの説明

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.

IPD 共有時間枠

On request following publication of the primary manuscript.

IPD 共有アクセス基準

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.

IPD 共有サポート情報タイプ

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE

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