Objective
Proton-activated currents (or acid-evoked currents, or acid-sensing ionic channels, ASICs) are highly represented in mammalian sensory neurons including the small diameter, nociceptive neurons. Tissue damage consecutive to injury leads to tissue acidosis. Thus, it has been suggested that local pH changes may constitute a stimulus for peripheral nociceptors trough the activation of ASICs. However, the lack of specific ligands for ASICs has prevented the experimental examination of this hypothesis. Recently, it has been demonstrated that FMRFamide, a peptide found in invertebrates as well as some related peptides including neuropeptide FF present in mammals, modulate currents flowing through acid-sensitive ionic channels (ASICs).
The general purpose of this work is to elucidate the role(s) of ASICs in the transduction of sensory signals by primary nociceptor neurons, identifying specific molecules that may interfere with ASICs and evaluating their effect on the activation of peripheral nociceptors. For this purpose, the skills of electrophysiologists, molecular biologists and chemists will be combined.
The main objectives are:
1) Study of the modulating action(s) of endogenous neuropeptides and neurotoxins of different origins on the acid-sensing ionic channels (ASICs);
2) Obtention of synthetic substances that mimic the effects of natural ligands on the ASICs. 3) Analysis of the physiological effects of the tested/newly created molecular principles in various models of nociception, both in normal animals and in knock-out mice strains deprived of specific ASIC subunits.
The project will contribute to understand the role(s) of ASICs in the origin of pain, opening new possibilities for its pharmacological control.
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding Scheme
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Coordinator
03550 San Juan de Alicante
Spain
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.