Objective Pain arises when a stimulus activates a pain-specific nerve fibre by opening an ion channel, causing a depolarisation (positive change in membrane potential) and triggering action potentials that propagate to the central nervous system to elicit a sensation of pain. The rate of depolarisation between action potentials determines their frequency, and thus the pain intensity. An important modulator of this rate is the hyperpolarisation-activated inward current, Ih. Ih ion channels are made up from combinations of four different subunits, HCN1-4. We have shown that the fast HCN1 subunits are expressed in large neurones sensing light touch, and the slower HCN2 in small pain-sensitive neurones. We aim to find out more about which subunits are expressed in which types of sensory neurones, and how their behaviour is modulated by inflammatory mediators. Neuropathic pain, an anomalous pain state characterised by ongoing pain and hypersensitivity, is not well understood and causes a substantial reduction in quality of life for those who suffer from it. There is evidence that Ih is involved in neuropathic pain, but which subunit is important and how it enhances neuropathic pain is unknown. We will tackle these and other questions by the use of mice in which each HCN subunit has been genetically deleted. We will record electrical responses from neurones in cell culture, where their behaviour can more readily be investigated. We will study the response of wild-type and HCN knockout mice to a mild painful stimulus. These studies will advance our understanding of the role of HCN subunits in pain, and if particular subunits have crucial roles in some aspects of pain (e.g. in neuropathic pain) the work will act as a stimulus to the development of novel drugs aimed at specifically blocking those subunits. Fields of science natural sciencesbiological sciencesneurobiology Keywords Biological sciences Health sciences Medical sciences Molecular biology Natural sciences Neurophysiology Neurosciences Physiology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) PEOPLE-2007-2-1.IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Call for proposal FP7-PEOPLE-2007-2-1-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE EU contribution € 178 874,06 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge United Kingdom See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Administrative Contact Peter Anthony Mcnaughton (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
