Early Postnatal Loss of Heat Sensitivity Among Cutaneous Myelinated Nociceptors in Swiss–Webster Mice

Abstract

Cutaneous myelinated nociceptors are known to exhibit considerable heterogeneity in their response to noxious heat. In the present experiments, we studied heat sensitivity among myelinated nociceptors during early postnatal life to determine whether this heterogeneity is correlated with other physiological and anatomical properties. A total of 129 cutaneous myelinated nociceptors were recorded intracellularly and characterized using mechanical and thermal skin stimuli in ex vivo preparations from neonatal Swiss-Webster (SW) mice across postnatal ages P2-P10; physiologically identified cells were iontophoretically labeled with neurobiotin for analyses of dorsal horn terminations from heat-sensitive and heat-insensitive cells. Our results show that heat sensitivity is not strictly correlated with other physiological or anatomical properties, most notably mechanical threshold or laminar termination patterns, of myelinated nociceptors at these ages. Further, we found a marked decline in the number of heat-sensitive myelinated mechanonociceptors (A-mechanoheat nociceptors [AMHs]) during this early postnatal period. Indeed, 68% of myelinated nociceptors were AMHs between P2 and P5, whereas this percentage dropped to 36% between P6 and P10. Multiple independent lines of evidence suggest that this decrease reflects a change in phenotype in a subset of myelinated nociceptors that lose sensitivity to noxious heat in early postnatal life. Interestingly, evidence was also obtained for a significant strain difference since the early transient excess in the number of AMHs in P2-P5 SW neonates was not present in similarly aged neonates from the C57Bl/6 strain. Potential mechanisms underlying these postnatal changes in AMH number are discussed.