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

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.

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