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dc.contributor.advisorMcCarson, Kenneth E.
dc.contributor.authorRook, Jerri Michelle
dc.date.accessioned2008-09-29T05:00:49Z
dc.date.available2008-09-29T05:00:49Z
dc.date.issued2008-07-16
dc.date.submitted2008
dc.identifier.otherhttp://dissertations2.umi.com/ku:2638
dc.identifier.urihttp://hdl.handle.net/1808/4232
dc.description.abstractTopically applied morphine is routinely used to alleviate pain in cutaneous wounds such as burns and pressure sores, yet evidence suggests the topical administration of exogenous opioid drugs may impair wound closure. This dissertation research was designed to test the hypothesis that topical morphine application delays cutaneous wound healing via mechanisms dependent upon peripheral neuropeptide activity. Results demonstrate that topical morphine application delays cutaneous wound closure rates. The delay occurs in a concentration-dependent manner (consistent with opioid-receptor mediated effects), is mimicked by NK-1 and NK-2 receptor antagonists, and can be reversed by the exogenous application of either substance P or neurokinin A. The results indicate that morphine acts presynaptically, delaying wound closure by activating opioid receptors located on primary afferent nerve terminals and subsequently inhibiting the antidromic release of neuropeptides into the wound. The temporal pattern of the effects of topical morphine treatment can be attributed to alterations in the initiation and duration of essential, early processes during wound healing. The delay in closure evoked by topical morphine not only leaves the cutaneous wound open longer, increasing the risk of infection, but also results in long-term architectural deficits, compromising the integrity of the healed skin. Furthermore, dysregulation of neurokinin receptor-expressing cells essential for normal wound healing emerges as a mechanism capable of significantly disrupting the dynamic processes involved in wound healing.
dc.format.extent171 pages
dc.language.isoEN
dc.publisherUniversity of Kansas
dc.rightsThis item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
dc.subjectHealth sciences
dc.subjectPharmacology
dc.titleMechanisms of Cutaneous Wound Healing are Mediated via Peripheral Neuropeptide Activity
dc.typeDissertation
dc.contributor.cmtememberCopple, Bryan
dc.contributor.cmtememberEnna, S. J.
dc.contributor.cmtememberPazdernik, Thomas L.
dc.contributor.cmtememberSmith, Peter
dc.thesis.degreeDisciplinePharmacology, Toxicology & Therapeutics
dc.thesis.degreeLevelPH.D.
kusw.oastatusna
kusw.oapolicyThis item does not meet KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


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