33: Mind the (Translational) Gap: Examining Cross-Species Variability in Quantitative Sensory Testing

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Assessment and Measurement of Pain/Nociception

Background and Aims: Understanding cross-species comparability in quantitative sensory testing (QST) is essential for bridging preclinical and clinical pain research. QST measurements are discussed as potential clinically relevant biomarkers [1], yet the translational gap between species remains a challenge. Although humans and rats share nociceptive pathways, the extent of variability in QST between species remains unclear. Rat studies involve genetically homogenous groups, controlled environments, and more direct signal detection [2], whereas humans exhibit substantial variability and rely on subjective pain ratings [3]. This discrepancy may contribute to high clinical trial failure rates. This study compared human and rat variability across seven QST measurements.

Methods: Healthy human and rat datasets were analysed across seven QST measurements: pinprick sensitivity (67 humans, 34 rats), windup ratios (40 humans, 108 rats), conditioned pain modulation (CPM; 76 humans), diffuse noxious inhibitory control (DNIC; 32 rats), offset analgesia (51 humans, 40 rats), onset hyperalgesia (51 humans, 40 rats), and heat pain thresholds (56 humans, 38 rats). Variables with differential measurement scales were presented as ratios, percentages, or log₁₀ transformed. Variability within each species was quantified using the median absolute deviation (MAD), which allowed comparability. Differences in variability between species were assessed using the Brown–Forsythe test and median-centred Levene’s tests.

Results: MADs differed across measurements: pinprick 64 mN (humans 0.301, rats 0.090) and 128 mN (0.347, 0.070), windup (0.73, 0.42), CPM/DNIC (17.2, 8.13), offset analgesia (21.9, 13.5), onset hyperalgesia (15.1, 11.1), and heat pain thresholds (1.65, 2.08). Pinprick sensitivity at 64 mN (p<0.001) and 128 mN (p<0.001), CPM/DNIC (p<0.01), offset analgesia (p<0.001), and onset hyperalgesia (p<0.05) had significantly different variability. In contrast, windup ratios (p=0.445) and heat pain thresholds (p=0.117) showed comparable variability across species. Finally, the results for onset hyperalgesia differed between the Brown-Forsythe (p<0.05) and Levene’s tests (p=0.110).

Conclusions: This study shows that cross-species variability differs markedly across several QST measurements, with generally larger variability found in humans than in rats. Pinprick sensitivity, CPM/DNIC, offset analgesia, and onset hyperalgesia demonstrated significant variability differences, suggesting limited translatability for these measures. In contrast, windup ratios and heat pain thresholds showed comparable variability, highlighting them as potential translational endpoints. These findings emphasize the importance of evaluating variability in animal and human pain research. Identifying QST measures with consistent variance across species may improve mechanistic interpretation and strengthen translational reliability in pain studies.

References: [1] Mackey, S., Aghaeepour, N., Gaudilliere, B., et al. Innovations in acute and chronic pain biomarkers: enhancing diagnosis and personalized therapy. Reg Anesth Pain Med, 2025.
[2] Klinck, M.P., Mogil, J.S., Moreau, M., et al. Translational pain assessment: Could natural animal models be the missing link? Pain, 2017.
[3] Nir, R.R., Yarnitsky, D. Conditioned pain modulation. Curr Opin Support Palliat Care, 2015, 9: 131–137.

Presenting Author: Emma Hertel
Submitting Author: Emma Hertel

Senior Author: Kirsty Bannister

IASP 2026 Global Year theme of Neuropathic Pain: No

• Emma Hertel - Aalborg University
• Ryan Patel - Imperial College London
• Kristian Kjær-Staal Petersen - Aalborg University
• Kirsty Bannister - Imperial College London