Background & Aims
Testing the function of the nociceptive system has been done for several decades in both research and the clinic. One testing modality often used is thermal stimuli, and in particular heating the skin using either thermodes or lasers. The testing most often involves the determination of thresholds such as detection and pain thresholds, typically defined as warm detection threshold (WDT) and heat pain threshold (HPT) (Rolke et al., 2006). These thresholds describe the skin surface temperature at the various thresholds – but do not describe the actual receptor temperature. The discrepancy between surface temperature and receptor temperature increases with increasing stimulation ramp, resulting in higher thresholds for steeper ramps (Pertovaara et al., 1996), so far the receptor thresholds are not known in detail or estimated based on surface temperature (Churyukanov et al., 2012). Thus, the aim of this study was to estimate the actual receptor temperature underlying the WDT and HPT.
Methods
In this combined experimental and computational modeling study, WDT and HPT were evaluated in 8 healthy subjects using four different temperature ramps (0.5, 1, 2, 4 °C/s). Subjects were asked to indicate when they felt a temperature increase (WDT) or when the temperature became painful (HPT). The computational model was based on previously developed models (Frahm et al., 2020; Lejeune et al., 2023).
The experimental values for WDT and HPT were analyzed using a Repeated Measures ANOVA and the data was combined with the model to find thermal threshold across the four temperature ramps, which was assumed to be identical across ramps (Tillman et al., 1995). To do this, the temperature at the dermo-epidermal junction (DEJ) (Frahm et al., 2010) was estimated across the four ramps and estimating the same conduction latency across all ramps the threshold was estimated as that latency with highest agreements across all ramps.
Results
In this preliminary study it was shown that both WDT and HPT increased significantly with increasing temperature ramp (RM ANOVA, p<0.001). The lowest WDT was 34.2±2.7 °C (for a ramp of 0.5 °C/s), and the highest WDT was 38.0±3.5 °C (for a ramp of 4°C/s). The lowest HPT was 43.7±3.2 °C (for a ramp of 0.5 °C/s), and the highest HPT was 47.8±4.0 °C (for a ramp of 4°C/s). The computational model consistently showed that the discrepancy between surface and receptor temperatures increased with steeper ramps. Furthermore, the computational model estimated the thermal for C-warmth fibers to 33.5±0.3°C and the threshold for C nociceptive fibers was estimated to 42.9±0.6°C. *Final results will be presented at IASP 2024 World Congress on Pain.
Conclusions
In this study the thermal thresholds for the primary afferents underlying the WDT and HPT was estimated using a joint experimental and computational approach. As expected both WDT and HPT increased with steeper ramps, and the model showed that is likely due to the discrepancy between surface and receptor temperatures. However, the model was able to estimate the receptor temperature threshold for those afferent activated during assessment of both WDT and HPT.
It is believed that the WDT is a measure of the function of C warmth fibers (Hallin et al., 1981; Lamotte & Campbell, 1978), whereas HPT is measure of primarily nociceptive C and possibly A? fibers (Pertovaara et al., 1996). The current estimates are lower than previous estimates of C fiber threshold (Churyukanov et al., 2012), but this is like due to previous estimates were based on surface temperature rather than actual receptor temperature.
References
Churyukanov, M., Plaghki, L., Legrain, V., & Mouraux, A. (2012). Thermal Detection Thresholds of A?- and C-Fibre Afferents Activated by Brief CO2 Laser Pulses Applied onto the Human Hairy Skin. PLoS ONE, 7(4), 1–10.
Frahm, K. S., Andersen, O. K., Arendt-Nielsen, L., & Mørch, C. D. (2010). Spatial temperature distribution in human hairy and glabrous skin after infrared CO2 laser radiation. Biomedical Engineering Online, 9(1), 69.
Frahm, K. S., Gervasio, S., Arguissain, F., & Mouraux, A. (2020). New insights into cutaneous laser stimulation – dependency on skin and laser type. Neuroscience, 448, 71–84.
Hallin, R. G., Torebjörk, H. E., & Wiesenfeld, Z. (1981). Nociceptors and warm receptors innervated by C fibres in human skin. Journal of Neurology, Neurosurgery, and Psychiatry, 44, 313–319.
Lamotte, R. H., & Campbell, J. N. (1978). Comparison of Responses of Warm and Nociceptive C-Fiber Merents in Monkey With Human Judgments of Thermal Pain. Jpurnal of Neurophysiology, 41(2), 509–528.
Lejeune, N., Petrossova, E., Frahm, K. S., & Mouraux, A. (2023). High-speed heating of the skin using a contact thermode elicits brain responses comparable to CO2 laser-evoked potentials. Clinical Neurophysiology, 146.
Pertovaara, A., Kauppila, T., & Hämäläinen, M. M. (1996). Influence of skin temperature on heat pain threshold in humans. Experimental Brain Research, 107(3), 497–503.
Rolke, R., Magerl, W., Campbell, K. A., Schalber, C., Caspari, S., Birklein, F., & Treede, R. D. (2006). Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur.J.Pain, 10(1090-3801 (Print)), 77–88.
Tillman, D. B., Treede, R. D., Meyer, R. A., & Campbell, J. N. (1995). Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: estimates of receptor depth and threshold. The Journal of Physiology, 485(3), 753–765.
Presenting Author
Steffen Frahm
Poster Authors
Topics
- Novel Experimental/Analytic Approaches/Tools