Sensory peptides as neuromodulators of wound healing in aged rats

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.