An intact nociceptor system of primary afferent sensory nerves is important for the initiation of the inflammatory process and successful tissue repair. Dysfunction of this system with age could be a contributing factor for delayed wound healing in the elderly. This study was designed to examine the role of sensory nerves (using
capsaicin-pretreated rats) and the effect of aging on the healing of a thermal
wound induced on the interscapular region (using a
CO2 laser). The healing endpoint was the time when full
wound contraction had occurred. The ability of the sensory
peptides,
substance P (SP) and
calcitonin gene-related peptide (CGRP), in modulating wound healing in aged rats was examined by taking into account the modulatory interaction effects between these
peptides. A
blister model in the rat hind footpad combined with a
laser Doppler
flowmeter was used initially to establish these vascular interaction effects. The results showed a significant delay in thermal wound healing in both the
capsaicin-treated and aged rats. Using the
blister model, we demonstrated the ability of SP and CGRP to induce a limited and a prolonged
vasodilator response, respectively. When tested together, SP attenuated the vascular effect of CGRP, an effect that was reversed using the
tachykinin antagonist
spantide II. When injected at the
wound site, SP and CGRP were equally potent in promoting wound healing in aged rats. The beneficial effect of taking the interaction effects into account was most evident in a group of rats that received the
tachykinin antagonist as part of their initial treatment with CGRP and 6 h later, an injection of SP; the time to complete
wound closure was 11.3 +/- 0.6 days compared to 21.0 +/- 0.9 days in aged controls. We contend that would healing in aged rats can be accelerated by exogenous administration of sensory
peptides. Furthermore, modulatory interaction effects between sensory
peptides should be taken into consideration when designing any treatment protocol that purports to accelerate wound healing.