| Cutaneous wound healing is a complex multifactorial process which occurs in three overlapping and yet distinct phases: inflammation, repair, and remodeling. The peripheral nerve system composed of C-fiber sensory afferent neurons and sympathetic post-ganglionic neurons (SPGNs) which innervate the skin is known to induce neurogenic inflammation following skin injury. However, little is known about the role of these peripheral nerves in cutaneous wound healing at the present time. The objective of this study was to investigate the role of SPGNs on cutaneous wound healing. A full-thickness incisional wound was created on the dorsal skin of the rat and left to heal by secondary intention. Cutaneous wound healing was assessed at the epidermal and dermal levels up to 15 days post-operatively, using the transcutaneous electrical resistance method and wound breaking strength test, respectively. Chemical sympathectomy significantly reduced epidermal healing in rats by 37% compared with vehicle-treated controls. On the other hand, chemical SPGN stimulation by injecting a sympathomimetic dose of 6-OHDA on days 0--3 post-operatively significantly accelerated epidermal healing by 35% and dermal healing by 43%, compared with time-matched controls.;The endogenous peptide bradykinin (BK) can potently trigger the neurogenic inflammatory reaction and mimic the neurogenic inflammation caused by low dose 6-OHDA. Thus, using the same injection paradigm as in the low-dose 6-OHDA treatment described above, it was observed that BK treatment significantly accelerated epidermal healing by 31% and dermal healing by 19%. Furthermore, using the BK B2 analog, RMP-7, epidermal healing was accelerated by 34% and dermal healing increased by 16%. The effects of BK and RMP-7 were demonstrated to be dependent on SPGNs using chemical sympathectomy.;Taken together, the results obtained from this research project demonstrate for the first time that the sympathetic nervous system plays an important role in cutaneous wound healing in the rat at both the epidermal and dermal levels. This information provides important new insights into the understanding of the pathophysiology of wound healing and could lead to new healing and could lead to new modalities for the management of impaired wound healing in conditions such as paraplegia, diabetes, skin diseases, and after radiotherapy for neoplasia. |
