Chronic pain: Molecular and cellular mechanisms
Group leader : A. Moqrich
Our team aims at understand the specification of heterogeneity in somatic sensory neurons.
Nociception is the afferent activity produced in the peripheral and central nervous systems by stimuli that have the potential to damage tissue. This activity is initiated by nociceptors, (also called pain receptors), that can detect mechanical, thermal or chemical changes above a set threshold. Once stimulated, a nociceptor transmits a signal along the spinal cord, to the brain.
Nociceptors convey a large cohort of perceptual sensory modalities including thermal, mechanical and chemical stimuli. These 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.
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.
To address this question, we use the mouse as model organism. The mouse has several advantages such as generation of transgenic models in which a gene can be inactivated, ectopically overexpressed or a combination of both in a tissue specific manner. The mouse genome is very close to that of humans and many debilitating human pathological conditions can be mimicked in mice.
We have designed a strategy aimed at expanding the molecular characterization of the nociceptive system by identifying new factors expressed in specific subsets of dorsal root ganglion neurons. For each of these newly identified neuronal markers, a sophisticated mouse model is being engineered. In these mice, each candidate gene is being conditionally inactivated by knocking-in an inducible killer molecule that will specifically ablate discrete subpopulations of nociceptive neurons marked by each of our candidate genes.
These mice models, in addition to deciphering the function of our candidate genes in the specification and function of primary sensory neurons, they will be used as unique cell ablation models, providing new insights into the functional specialization of discrete subclasses of primary nociceptive neurons. Conditional inactivation of a given target gene, and the use of the regulatory elements of this same target gene to drive the expression of an inducible killer molecule in a living animal represents the most innovative, specific and powerful approach to determine functions of specific neuronal subtypes.
Results emanating from this work will provide hints on how a precise neuronal subtype is generated, how it matures and what kind of particular sensory modalities it perceives.
February 27th, 2017
Genetic ablation of GINIP-expressing primary sensory neurons strongly impairs Formalin-evoked pain.
February 12th, 2015
Transcriptional Profiling of Cutaneous MRGPRD Free Nerve Endings and C-LTMRs.
September 17th, 2014
GINIP, a Gαi-Interacting Protein, Functions as a Key Modulator of Peripheral GABAB Receptor-Mediated Analgesia.
February 6th, 2014
Uncoupling of Molecular Maturation from Peripheral Target Innervation in Nociceptors Expressing a Chimeric TrkA/TrkC Receptor.
January 30th, 2014
Peripheral pain-sensing neurons: from molecular diversity to functional specialization.
October 31st, 2013
TAFA4, a Chemokine-like Protein, Modulates Injury-Induced Mechanical and Chemical Pain Hypersensitivity in Mice.
September 15th, 2010
Hepatocyte growth factor-Met signaling is required for Runx1 extinction and peptidergic differentiation in primary nociceptive neurons.
March 4th, 2005
Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin.
August 7th, 2004
Expressing TrkC from the TrkA locus causes a subset of DRG neurons to switch fate.
January 14th, 2015
The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function.
June 12th, 2014
Acute heat-evoked temperature sensation is impaired but not abolished in mice lacking TRPV1 and TRPV3 channels.
September 25th, 2013
Sodium-mediated plateau potentials in lumbar motoneurons of neonatal rats.
October 1st, 2010
stac1 and stac2 genes define discrete and distinct subsets of dorsal root ganglia neurons.
October 1st, 2010
Heterogeneity in primary nociceptive neurons: from molecules to pathology.
October 1st, 2009