Session-Order Sensitivity of TS and OA in a Capsaicin Crossover Model (TS-OA-Cap)
2026년 6월 3일 업데이트: 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.
연구 개요
상태
완전한
상세 설명
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).
연구 유형
중재적
등록 (실제)
16
단계
- 해당 없음
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Ontario
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Guelph, Ontario, 캐나다, N1G2W1
- Human Health Sciences, University of Guelph
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
예
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 무작위
- 중재 모델: 크로스오버 할당
- 마스킹: 삼루타
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: 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.
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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.
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.
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활성 비교기: 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.
|
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.
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.
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Mechanical temporal summation (Sumscore)
기간: Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
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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.
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Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
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Offset analgesia magnitude (OffA)
기간: Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
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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.
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Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Within-session temporal stability (ICC(2,1)) of Sumscore and OffA
기간: 10, 20, 30, and 40 minutes post-intervention
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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.
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10, 20, 30, and 40 minutes post-intervention
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Differential design-sensitivity (Measure × Intervention × Period interaction)
기간: 10, 20, 30, and 40 minutes post-intervention, across two crossover periods separated by a minimum 1-week washout.
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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.
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10, 20, 30, and 40 minutes post-intervention, across two crossover periods separated by a minimum 1-week washout.
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Grill JD, Coghill RC. Transient analgesia evoked by noxious stimulus offset. J Neurophysiol. 2002 Apr;87(4):2205-8. doi: 10.1152/jn.00730.2001.
- Dwan K, Li T, Altman DG, Elbourne D. CONSORT 2010 statement: extension to randomised crossover trials. BMJ. 2019 Jul 31;366:l4378. doi: 10.1136/bmj.l4378.
- Clouse JA, et al. The reliability of a temporal summation Sumscore. (2021)
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2024년 5월 1일
기본 완료 (실제)
2025년 4월 30일
연구 완료 (실제)
2025년 4월 30일
연구 등록 날짜
최초 제출
2026년 5월 22일
QC 기준을 충족하는 최초 제출
2026년 6월 3일
처음 게시됨 (실제)
2026년 6월 4일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2026년 6월 4일
QC 기준을 충족하는 마지막 업데이트 제출
2026년 6월 3일
마지막으로 확인됨
2026년 6월 1일
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- GUELPH-REB-19-06-003
- REB #19-06-003 (기타 식별자: University of Guelph)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
예
IPD 계획 설명
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 공유 기간
On request following publication of the primary manuscript.
IPD 공유 액세스 기준
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 공유 지원 정보 유형
- 연구_프로토콜
- 수액
- ICF
- ANALYTIC_CODE
약물 및 장치 정보, 연구 문서
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아니
미국 FDA 규제 기기 제품 연구
아니
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