EFFECTS OF AGING ON SENSORY NERVE FUNCTION IN RAT SKIN

Human studies have shown an age-related decrease in modulation of skin vascular reactivity by sensory nerves that correlates with a decline in wound repair efficacy. Using a vacuum-induced blister model in the rat hind footpad, we have investigated age-related changes in pre- and post-terminal activity of primary afferents involved in skin neurovas cular function. Changes in local skin blood flow were monitored using a laser Doppler flowmeter. Pre-terminal stimulation was achieved by el ectrical stimulation of the distal end of the sciatic nerve (10 V, 15 Hz and 0.5 ms) in three groups of young, old and neonatally pretreated capsaicin rats (3, 24 and 3 months old, respectively). The effect of post-terminal stimulation, achieved using local perfusion of 1 muM sub stance P (SP) over the blister base, was examined in young (3 months o ld), mature (12 months old) and aged (24 months old) rats. In addition to changes in SP responsiveness, other post-terminal changes studied included changes in smooth muscle reactivity to sodium nitroprusside ( SNP), which acts directly on smooth muscle and to endothelial cell fun ction using N-nitro-L-arginine (L-NORAG), a selective inhibitor of nit ric oxide synthesis and endothelium-dependent relaxation. Electrical s timulation of the sciatic nerve in young rats induced an increase in l ocal blood flow (within 1 min) that was maintained during the stimulat ion period, while the capsaicin group and the old group showed a signi ficantly increased latency and decreased amplitude of the response. Pe rfusion of SP resulted in an increase in skin blood flow that underwen t tachyphylaxis in young rats, but which was significantly enhanced an d maintained in old rats. There was no difference in the vasodilator r esponse to SNP with age. On the other hand, there was an age-dependent increase in the contribution of endothelial mechanisms involving NO. Our study suggests that both pre- and post-nerve terminal function cha nges with ageing of the peripheral neurovascular apparatus. The simila rity of the responses to electrical stimulation in capsaicin pretreate d and old rats suggests similar pre-terminal mechanisms operate in the two groups, namely a decrease in the number of sensory nerves present and/or a decrease in their peptide content. The altered profile of th e response to SP with age is suggestive of changes in post-terminal me chanisms involved in tachyphylaxis to SP. It is suggested that tachyki nin receptors in old rats are up-regulated as a consequence of a pre-t erminal defect in peptide release mechanisms of sensory nerves.