Cutaneous C-fiber nociceptor responses and nociceptive behaviors in aged Sprague-Dawley rats.

Abstract The change with age in pain perception in humans and the nociceptive behaviors in animals elicited by noxious stimuli to the skin are not well understood, and little is known about the peripheral neural mechanisms of cutaneous nociception in the aged. We systematically examined cutaneous nociceptor responses and nociceptive behaviors in young (9–14 w) and in aged (127–138 w) Sprague–Dawley rats. C-fiber nociceptors in the skin were identified by mechanical and electrical stimulation, and extracellularly recorded from hind paw skin-saphenous nerve preparations in vitro . In the aged rats, the proportions of mechano-responsive and/or heat-responsive C-nociceptors were significantly lower. The proportion of mechano- and thermo-insensitive units, on the other hand, was significantly increased. In addition, the response threshold to mechanical stimulus tended to be higher and the magnitude of the response tended to be smaller. There were no differences between the two age groups in the response magnitudes of mechano-responsive C-nociceptors to bradykinin, cold or heat. Repetitive electrical stimulation of afferent fibers revealed exaggerated slowing of conduction velocity in mechano-responsive C-fibers in the aged. This showed for the first time that not only receptive properties of afferent terminals but also membrane properties of conducting axons are changed in aged rats. Nociceptive behaviors in response to noxious levels of cold (cold plate test) and heat (Hargreaves’ radiant heat test) were facilitated in aged animals, while mechanical sensitivity measured by von Frey hairs remained unchanged. These discrepancies between the changes in peripheral afferents and the behavioral outcomes might be explained by facilitatory changes in the central nervous system.