Differential activation of trigeminal C or Aδ nociceptors by infrared diode laser in rats: Behavioral evidence

Radiant heat is often used for studying thermal nociception, although inherent characteristics such as the broad spectrum of applied wavelengths of typical light sources limit control over and repeatability of stimuli. To overcome these problems, we used a diode infrared laser-based stimulator (wavelength: 980 nm) for selectively stimulating trigeminal Aδ or C thermonociceptors in rats. To provide indirect evidence for nociceptor-selective stimulation, we tested the effects of capsaicin, dimethylsulfoxide (DMSO), and morphine on withdrawal latencies for long pulses with a low current (hypothesized to selectively stimulate C nociceptors) and for threshold currents of short pulses with high current (hypothesized to selectively stimulate Aδ nociceptors) in lightly anesthetized rats. Nonmem® analysis was used to perform pharmacodynamic modeling. The measured baseline withdrawal latency for long pulses was 12.5 ± 0.3 s which was changed significantly to 6.7 ± 0.4 s after applying topical capsaicin which selectively sensitizes C nociceptors and to 16.5 ± 1.3 s after 1.0 mg/kg morphine which preferentially attenuates C fiber nociception. Topical DMSO which appears to selectively sensitize Aδ afferents did not significantly alter withdrawal latencies to the long pulses. Fitted threshold currents for short pulses after DMSO were however significantly lower (974 ± 53 mA vs. 1113 ± 12 mA for baseline) indicating Aδ sensitization. Capsaicin and morphine did not significantly change threshold currents. Best Nonmem® fits for the long pulse were obtained using a model assuming no DMSO effect, but a different inter-individual variability after applying this substance. For the short pulse, a model assuming no capsaicin or morphine effect, but again allowing different inter-individual variabilities after applying these drugs, best described the data. We conclude that different settings of the stimulator used in this study were capable of selectively activating trigeminal Aδ or C thermonociceptors.