Mechanisms underlying disordered skin blood flow following nerve injury [ 2005 - 2007 ]

Research Grant

Researchers: A/Pr James Brock (Principal investigator) ,  E/Pr Elspeth Mclachlan

Brief description Many people who recover from traumatic injury or who have chronic conditions such as diabetes or neuropathy from exposure to a toxic chemical suffer from peripheral vascular disorders leading to poor circulation in the extremities. These conditions are characterised by impaired wound healing, cold hands and feet and ongoing pain. These people must face a long life with progressively increasing disability. Even normal ageing can lead to similar problems. This project is directed at understanding the role of the nerve supply to blood vessels in the skin in these disorders. The experiments will be conducted in skin blood vessels of rats with various forms of nerve lesion that will mimic these conditions in patients. We will use our knowledge of the structure and behaviour of nerve-blood vessel connections to analyse the changes in the properties of vascular smooth muscle and relate it to the state of the innervation. Skin arteries normally receive two types of nerve - sympathetic (which release noradrenaline) and afferent ( which release peptides) - that have opposing actions on the vessel (constriction and dilation respectively). We hypothesize that removal of part or all of the innervation changes the contractile mechanism of the smooth muscle in the wall of the vessel so that it becomes much more sensitive to calcium ions and produces larger and more prolonged contractions. We will combine electrophysiology and contraction studies with immunohistochemistry and biochemical analysis to define the relation between the nerve deficit and the vascular responses. The aim is to identify appropriate drug targets for which local application in the affected region can alleviate the symptoms without causing widespread side effects.

Funding Amount $AUD 408,000.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant