PROJECT: JTC2012: LIGHTPAIN

Deciphering the role of peripheral and central nervous system metabotropic glutamate receptors in neurophatic pain with photoactivable ligands

Abstract

Optogenetic approaches are viewed as very promising approaches to tackle physiological processes, and eventually for space and time-controlled therapeutic interventions. However, the need for transgenes limits the development of these approaches. An alternative is based on optopharmacology, which consists of using light-activable compounds that can reach their target only upon light activation. The LIGHTPAIN project is aimed at developing photo-activable ligands targeting selectively metabotropic glutamate (mGlu) receptors, which represent promising drug targets for pain control. The ultimate objectives are directed to understand the role of the different mGlu receptor subtypes at different sites of the nervous system in regulating pain transmission. These light-controlled molecules and the techniques for optical ligand delivery to the spinal cord, brain and peripheral nerves will be used to understand how mGlu receptors critically regulate pain threshold under pathological conditions. The LIGHTPAIN project specifically addresses this issue using subtype-selective mGlu receptor ligands ( positive or negative allosteric modulators) that are photochemically triggered and can therefore interact with mGlu receptors only at sites (peripheral or central) that are spatiotemporally exposed to light.

Keywords

Pharmacology, Glutamate, GPCR, metabotropic glutamate receptors, Photochemistry, Light activated ligands, pheripheral nervous system, central nervous system, photostimulation, neural circuits, Light, caged compounds, chronic pain, neurophatic pain

Call topic

New Methods

Proposed runtime

2013 - 2016

Project team

Amadeu Llebaria (Coordinator)
Spain (MINECO)
Jes£s Giraldo
Spain (MINECO)
Francisco Ciruela
Spain (MINECO)
Ferdinando Nicoletti
Italy (MOH)
Jean-Philippe Pin
France (ANR)