TEAM

Chronic pain: Molecular and cellular mechanisms

Group leader : A. Moqrich

Our team aims at understand the specification of heterogeneity in somatic sensory neurons.

FOR BEGINNERS
Pic3

A DRG section double stained with two newly identified genes expressed in a partially overlapping manner.

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.

Pic6

A dorsal horn spinal cord section double stained with IB4 and EGFP-expressing C-LTMRs.

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.

FOR SPECIALISTS
Pic10

High magnification of a hair follicle surrounded by an EGFP-expressing C-LTMR fiber

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.

Pic9

EGFP-expressing C-LTMRs peripheral fiber nicely connecting mouse hair follicles in the hairy skin

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.


Main publications

PUBLICATION

Genetic ablation of GINIP-expressing primary sensory neurons strongly impairs Formalin-evoked pain.

Urien L, Gaillard S, Lo Re L, Malapert P, Bohic M, Reynders A, Moqrich A.
Sci Rep. 2017 Feb 27;7:43493 PMID: 28240741

PUBLICATION

Transcriptional Profiling of Cutaneous MRGPRD Free Nerve Endings and C-LTMRs.

Reynders A, Mantilleri A, Malapert P, Rialle S, Nidelet S, Laffray S, Beurrier C, Bourinet E, Moqrich A.
Cell Rep. 2015 Feb 12. pii: S2211-1247(15)00047-9. PMID: 25683706

PUBLICATION

GINIP, a Gαi-Interacting Protein, Functions as a Key Modulator of Peripheral GABAB Receptor-Mediated Analgesia.

Gaillard S, Lo Re L, Mantilleri A, Hepp R, Urien L, Malapert P, Alonso S, Deage M, Kambrun C, Landry M, Low SA, Alloui A, Lambolez B, Scherrer G, Le Feuvre Y, Bourinet E, Moqrich A.
Neuron. 2014 Sep 17. pii: S0896-6273(14)00786-7. doi: 10.1016/j.neuron.2014.08.056. PMID: 25242222

PUBLICATION

Uncoupling of Molecular Maturation from Peripheral Target Innervation in Nociceptors Expressing a Chimeric TrkA/TrkC Receptor.

Gorokhova S, Gaillard S, Urien L, Malapert P, Legha W, Baronian G, Desvignes JP, Alonso S, Moqrich A.
PLoS Genet. 2014 Feb 6;10(2):e1004081. PMID:24516396

PUBLICATION

Peripheral pain-sensing neurons: from molecular diversity to functional specialization.

Moqrich A.
Cell Rep. 2014 Jan 30;6(2):245-6. PMID:24484769

PUBLICATION

TAFA4, a Chemokine-like Protein, Modulates Injury-Induced Mechanical and Chemical Pain Hypersensitivity in Mice.

Delfini MC, Mantilleri A, Gaillard S, Hao J, Reynders A, Malapert P, Alonso S, François A, Barrere C, Seal R, Landry M, Eschallier A, Alloui A, Bourinet E, Delmas P, Le Feuvre Y, Moqrich A.
Cell Rep. 2013 Oct 31;5(2):378-88. PMID: 24139797

PUBLICATION

Hepatocyte growth factor-Met signaling is required for Runx1 extinction and peptidergic differentiation in primary nociceptive neurons.

Gascon E, Gaillard S, Malapert P, Liu Y, Rodat-Despoix L, Samokhvalov IM, Delmas P, Helmbacher F, Maina F, Moqrich A.
J Neurosci. 2010 Sep 15;30(37):12414-23. PMID: 20844136

PUBLICATION

Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin.

Moqrich A, Hwang SW, Earley TJ, Petrus MJ, Murray AN, Spencer KS, Andahazy M, Story GM, Patapoutian A.
Science. 2005 Mar 4;307(5714):1468-72. PMID: 15746429

PUBLICATION

Expressing TrkC from the TrkA locus causes a subset of DRG neurons to switch fate.

Moqrich A, Earley TJ, Watson J, Andahazy M, Backus C, Martin-Zanca D, Wright DE, Reichardt LF, Patapoutian A.
Nat Neurosci. 2004 Aug;7(8):812-8. PMID: 15247919
Other publications

PUBLICATION

The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function.

François A, Schüetter N, Laffray S, Sanguesa J, Pizzoccaro A, Dubel S, Mantilleri A, Nargeot J, Noël J, Wood JN, Moqrich A, Pongs O, Bourinet E.
Cell Rep. 2015 Jan 14. pii: S2211-1247(14)01095-X. PMID: 25600872

PUBLICATION

Acute heat-evoked temperature sensation is impaired but not abolished in mice lacking TRPV1 and TRPV3 channels.

Marics I, Malapert P, Reynders A, Gaillard S, Moqrich A.
PLoS One. 2014 Jun 12;9(6):e99828. PMID: 24925072

PUBLICATION

Sodium-mediated plateau potentials in lumbar motoneurons of neonatal rats.

Bouhadfane M, Tazerart S, Moqrich A, Vinay L, Brocard F.
J Neurosci. 2013 Sep 25;33(39):15626-41. PMID: 24068829

PUBLICATION

stac1 and stac2 genes define discrete and distinct subsets of dorsal root ganglia neurons.

Legha W, Gaillard S, Gascon E, Malapert P, Hocine M, Alonso S, Moqrich A.
Gene Expr Patterns. 2010 Oct-Dec;10(7-8):368-75. PMID: 20736085

PUBLICATION

Heterogeneity in primary nociceptive neurons: from molecules to pathology.

Gascon E, Moqrich A.
Arch Pharm Res. 2010 Oct;33(10):1489-507. PMID: 21052929

PUBLICATION

TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP.

Mandadi S, Sokabe T, Shibasaki K, Katanosaka K, Mizuno A, Moqrich A, Patapoutian A, Fukumi-Tominaga T, Mizumura K, Tominaga M.
Pflugers Arch. 2009 Oct;458(6):1093-102. PMID: 19669158

Interactions

IBDM
NATIONAL
  • P .Delmas, CRN2M Marseille
  • E. Bourinet, IGF Montpellier
  • Y. Lefeuvre, IINS Bordeaux
INTERNATIONAL
  • Qiufu Ma, Harvard Medical School
  • John Wood, UCL
  • Igor Samokhvalov, RIKEN Kobe
  • Fan Wang, Duke University
  • Wenqin Luo, UPENN
  • Makr Zylka, UNC-School of Medicine

IBDM animal houses staff
Transgenic animal services from Villejuif (SEAT)

Funding

ERC

AFM

ANR

FRM

 

ARC

 

Logo-ATIP-AVENIR

Members more

Manon Bohic Francis Castets Nadine Clerc Catarina De Pais Paiva Santos Stéphane Gaillard Anissa Jhumka Pascale Malapert Irène Marics Ana Reynders Sungjae Yoo
Aziz Moqrich
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Aziz Moqrich

Researcher

Manon Bohic
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Manon Bohic

PhD student

Francis Castets
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Francis Castets

Researcher

Nadine Clerc
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Nadine Clerc

Researcher

Catarina De Pais Paiva Santos
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Catarina De Pais Paiva Santos

PhD student

Stéphane Gaillard
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Stéphane Gaillard

Others

Anissa Jhumka
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Anissa Jhumka

PhD student

Pascale Malapert
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Pascale Malapert

Technical staff

Irène Marics
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Irène Marics

University lecturer

Ana Reynders
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Ana Reynders

Researcher

Sungjae Yoo
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Sungjae Yoo

Postdoctoral fellow

Overview

Model organism
Biological process studied
  • Specification of heterogeneity in somatic sensory neurons
Technical approaches
  • Transgenic mouse
  • RNA seq
Medical applications
  • Interactions cellulaires et adhésion. Nouvelles approches d’imagerie médicale