Introduction: 1.8 ion channels that are involved in the phenomenon of activity-dependent slowing (ADS) in C-fibre nociceptors. C-fibre ADS differs between the sexes and can regulate spinal network function. Objective: Explore the impact of methylglyoxal upon C-fibre ADS and pain sensitivity in both sexes. In addition, investigate the influence of ADS upon the processing of C-fibre inputs, in noxious heat responsive spinal neurons. Results: Compound action potential recording of isolated dorsal roots incubated with methylglyoxal (100 µM, 3 hours) revealed a sex-dependent impact upon C-fibre ADS. In male roots, C-fibre ADS was reduced, whereas in female roots, it was increased. Acute methylglyoxal application (100 µM/1 mM, 10 minutes) did not modify C-fibre ADS. Systemic methylglyoxal administration (5 μg, 3 h prior) induced heat hyperalgesia in male but not female juvenile rats. Patch-clamp recording in spinal slices with attached dorsal roots revealed that length-dependent manipulation of ADS altered action potential firing to stimulus trains in noxious heat responsive Fos-EGFP + spinal neurons. Conclusion: We propose that methylglyoxal sex-dependent regulation of C-fibre ADS influences the spinal processing of noxious heat inputs that may contribute to the male specific induction of heat hyperalgesia after systemic methylglyoxal treatment.
Velichkova et al. (Mon,) studied this question.