EXPRESS: Assessing Pain Sensitivity with COX-2 Biomarkers: A Novel Approach in Healthy Volunteers

Quantifying pain is challenging due to its subjective nature. An established baseline of COX-2 levels in healthy subjects under controlled thermal pain stimulation will help bridge subjective pain assessment and objective biological measurements. 34 healthy students (aged from 17 to 21 years) participated in two thermal-induced pain protocols: (i) a water bath (ranging from 29 to 47 °C), (ii) internal wrist stimulation via a TSA-II thermal probe. Pain assessment was assessed via the visual analog scale (VAS). A strong positive correlation was observed between temperature and VAS scores (Pearson's r = 0.94, p<0.001). Temperature and immersion time in the water bath protocol showed a strong inverse correlation (r=-0.95, p<0.001). The mean COX-2 levels in water bath and TSA-II experiments were 1.88 ± 0.81 ng/mL (95% CI: 1.62 to 2.14) and 2.16 ± 0.77 ng/mL (95% CI: 1.92 to 2.40), respectively. These values are 50 to 2000-fold lower than those reported in the prior emergency-room-based acute pain studies. Linear mixed-effects models demonstrated that temperature was the only significant predictor of VAS (p < 0.001), while COX-2 was not. Whereas, COX-2 expression was not explained by VAS or temperature, indicating stable baseline levels. This work has established an exploratory baseline study for COX-2 levels in healthy subjects. This stark contrast highlights the potential to discriminate between baseline healthy and pain states, representing a step toward the development of biomarker-based tools for assessment.