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.

Long-term follow-up of peptidergic and nonpeptidergic reinnervation of the epidermis following sciatic nerve reconstruction in rats

“…Since previous studies showed no significant age-related differences in withdrawal latency to hot temperatures 32 and mechanical stimuli 42 in adult rats, the end point of shamoperated rats was determined at 5 weeks postoperatively. In addition, as part of unpublished experiments, we have examined 3 sham-operated rats for behavioral but mainly for possible age-related changes in histological data at 30 weeks postoperatively.…”

Peripheral and spinal mechanisms of nociception in a rat reserpine-induced pain model

“…An activity-dependent change in conduction velocity (ADCCV) index was used for the single-fibers electrically identified in series 1. The methods used to obtain this index have been established in our previous report with the skin-nerve preparations, 53 but not with the muscle-nerve preparations.…”

Monocyte chemoattractant protein-1-induced excitation and sensitization to mechanical stimulation of mechanosensitive C-fiber afferents in rat skin

“…Rat hindpaw skin-saphenous nerve preparation was used, and the methods of recording single fiber activities, stimulation of the fibers and data analysis were basically the same as previously reported (Banik et al, 2001;Taguchi et al, 2010). Briefly, the skin from one or both hindlimbs was carefully removed with the saphenous nerve attached after CO 2 euthanasia.…”

“…We used the same response criteria as in our previous study with cutaneous afferents to determine whether a fiber was responsive to a stimulus (Taguchi et al, 2010). Specifically, a fiber was defined to be sensitive to mechanical stimulation when it fulfilled the following criteria: (1) the net increase in the discharge rate during the stimulus period was more than 0.1 imp/s over the background discharge rate (BDR) during the control period of 60 s immediately before the onset of the mechanical stimulus, and (2) the instantaneous discharge rate of two consecutive discharges exceeded the mean + 2 SD of the BDR.…”