PAINEURONS · Functional significance of nociceptive primary sensory neurons diversity

Unravelling the precise in vivo function of a particular neuronal subpopulation is one of the most challenging issues in neurobiology. Nociceptive primary sensory neurons represent a powerful model system to address this fundamental question. These neurons convey a large cohort of perceptual sensory modalities including thermal, mechanical and chemical stimuli from the periphery to the spinal cord. Nociceptive neurons encompass an extremely heterogeneous population with respect to their morphological, anatomical, electrophysiological and molecular properties. In spite of the efforts, the functional significance of this remarkable diversity has remained elusive. Our proposed project, show our contribution to the expansion of the repertoire of molecules specifying discrete subsets of primary nociceptive neurons and describes original and highly versatile mice models in which the loci of our favourite genes have been genetically engineered to allow conditional gene inactivation and inducible cell ablation of discrete nociceptive neuronal subtypes. Molecular, anatomical, physiological and behavioural analyses of such models will allow to (i) unravel the role of each of our favorite genes in the specification/function of the sensory neuronal subtypes and (ii) correlate discrete subsets of nociceptive neurons to clearly defined sensory modalities. Understanding how diversity in neuronal phenotypes is accomplished is only the first step to deepen into the mechanisms of pain. If we know how a precise neuronal subtype is generated, we can subsequently analyze not only basic aspects of its physiology, but also more medically oriented aspects like its functional role under pathological conditions, its chronic changes in response to inflammation and analgesic treatments