SENSORY PEPTIDES AS NEUROMODULATORS OF WOUND-HEALING IN AGED RATS

An intact nociceptor system of primary afferent sensory nerves is impo rtant for the initiation of the inflammatory process and successful ti ssue repair. Dysfunction of this system with age could be a contributi ng factor for delayed wound healing in the elderly. This study was des igned to examine the role of sensory nerves (using capsaicin-pretreate d rats) and rite effect of aging on the healing of a thermal wound ind uced on the interscapular region (using a CO2 laser). The healing endp oint was the time when full wound contraction had occurred. The abilit y of rite sensory peptides, substance P (SP) and calcitonin gene-relat ed peptide (CGRP), in modulating wound healing in aged rats was examin ed by taking into account the modulatory interaction effects between t hese peptides. A blister model in the rat hind footpad combined with a laser Doppler flowmeter was used initially to establish these vascula r interaction effects. The results showed a significant delay in therm al wound healing in both the capsaicin treated and aged rats. Using th e blister model, we demonstrated the ability of SP and CGRP to induce a limited and a prolonged vasodilator response, respectively. When tes ted together, SP attenuated the vascular effect of CGRP, an effect tha t was reversed using the tachykinin antagonist spantide II. When injec ted at the wound site, SP and CGRP were equally potent in promoting wo und healing in aged rats. The beneficial effect of taking the interact ion effects into account was most evident in a group of rats that rece ived the tachykinin antagonist as part of their initial treatment with CGRP and 6 h later, an injection of SP; the time to complete wound cl osure was 11.3 +/- 0.6 days compared to 21.0 +/- 0.9 days in aged cont rols. We contend that round healing in aged rats can be accelerated by exogenous administration of sensory peptides. Furthermore, modulatory interaction effects between sensory peptides should be taken into con sideration when designing any treatment protocol that purports to acce lerate wound healing.