Laser speckle contrast imaging as an objective physiological readout associated with pain and nociception

Abstract Background Pain is a subjective experience for which self-report remains the reference standard. We evaluated laser speckle contrast imaging (LSCI) as an objective, contact-free measure of peripheral microcirculation associated with acute pain in awake humans and with analgesia-modulated nociception-related responses in anaesthetised mice. Methods Sixty healthy volunteers were enrolled in three independently recruited, non-randomised parallel cohorts (pressure, cold, or electrical stimulation; n = 20 each); each participant received one stimulus titrated to the first numeric rating scale (NRS) score > 4. In 132 selected awake surgical patients, contralateral hand, wrist, or distal-forearm perfusion was recorded before and during right radial artery puncture and related to the immediate post-procedural NRS. Thirty male mice underwent plantar incision under propofol or isoflurane after saline, low-dose morphine, or high-dose morphine (n = 5 per anaesthetic–analgesic subgroup). An exploratory ratio-only LSCI Nociception Index (LNI) was developed and internally evaluated in the patient cohort. Results In each volunteer cohort, median and minimum perfusion decreased during individually titrated suprathreshold stimulation. In patients, median and minimum perfusion features correlated negatively with NRS pain intensity, and the ROI minimum ratio and difference had the strongest inverse associations with the full NRS score (Spearman’s ρ = −0.428 and −0.425, respectively; both P < 0.001). In an exploratory, same-cohort derivation, the LNI had an apparent in-sample AUC of 0.80 (95% CI 0.73–0.87) for NRS > 4, with a bootstrap optimism-corrected AUC of 0.79; these are internal estimates that require external validation. In anaesthetised mice, plantar incision produced stage-specific perfusion reductions, and morphine showed a dose-ordered pattern of attenuation of surgical perfusion reductions under both anaesthetic regimens, but the small subgroups and possible direct vascular effects of morphine limit interpretation. Conclusions LSCI captures peripheral perfusion changes associated with acute pain in awake humans and analgesia-modulated nociception in mice, providing proof-of-concept for its utility as a pain-related biomarker. However, the human results are restricted to selected populations, mouse findings are exploratory, the single-cohort derived LNI requires external validation and further dedicated studies are needed before its clinical monitoring application.