Chronic pain: Molecular and cellular mechanisms

Group leader : A. Moqrich

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


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.


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.


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.


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.

Selected publications


Loss of bhlha9 impairs thermotaxis and formalin-evoked pain in a sexually dimorphic manner

Manon Bohic, Irène Marics, Catarina Santos, Pascale Malapert, Nissim Ben Arie, Chiara Salio, Ana Reynders, Yves Le Feuvre, Andrew J.Saurin, Aziz Moqrich
Cell Rep, 30 (3), 602-610.e6 2020 Jan 21 PMID: 31968239


c-Jun/p38MAPK/ASIC3 Pathways Specifically Activated by NGF Through TrkA Is Crucial for Mechanical Allodynia Development

Tanguy Chaumette, Lauriane Delay, Julie Barbier, Ludivine Boudieu, Youssef Aissouni, Mathieu Meleine, Amandine Lashermes, Wassim Legha, Sophie Antraigue, Frederic Antonio Carvalho, Alain Eschalier, Denis Ardid, Aziz Moqrich, Fabien Marchand
Pain 2020 Jan 16 PMID: 31977937


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


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


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


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


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

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


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


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


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


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


A cell fitness selection model for neuronal survival during development

Wang Y, Wu H, Fontanet P, Codeluppi S, Akkuratova N, Petitpré C, Xue-Franzén Y, Niederreither K, Sharma A, Da Silva F, Comai G, Agirman G, Palumberi D, Linnarsson S, Adameyko I, Moqrich A, Schedl A, La Manno G, Hadjab S, Lallemend F.
Nat Commun. 2019 Sep 12;10(1):4137. doi: 10.1038/s41467-019-12119-3. PMID: 31515492


Cav3.2 T-type calcium channels shape electrical firing in mouse Lamina II neurons

Candelas M, Reynders A, Arango-Lievano M, Neumayer C, Fruquière A, Demes E, Hamid J, Lemmers C, Bernat C, Monteil A, Compan V, Laffray S, Inquimbert P, Le Feuvre Y, Zamponi GW, Moqrich A, Bourinet E, Méry PF.
Sci Rep. 2019 Feb 28;9(1):3112. doi: 10.1038/s41598-019-39703-3. 30816223


5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein-coupled receptor D

Bautzova T, Hockley JRF, Perez-Berezo T, Pujo J, Tranter MM, Desormeaux C, Barbaro MR, Basso L, Le Faouder P, Rolland C, Malapert P, Moqrich A, Eutamene H, Denadai-Souza A, Vergnolle N, Smith ESJ, Hughes DI, Barbara G, Dietrich G, Bulmer DC, Cenac N.
Sci Signal. 2018 Dec 18;11(561). pii: eaal2171. doi: 10.1126/scisignal.aal2171. PMID: 30563864


TAFA4 Reverses Mechanical Allodynia through Activation of GABAergic Transmission and Microglial Process Retraction

Kambrun C, Roca-Lapirot O, Salio C, Landry M, Moqrich A, Le Feuvre Y.
Cell Rep. 2018 Mar 13;22(11):2886-2897. doi: 10.1016/j.celrep.2018.02.068. PMID: 29539418


Disruption of TRPV3 Impairs Heat-Evoked Vasodilation and Thermoregulation: A Critical Role of CGRP

Fromy B, Josset-Lamaugarny A, Aimond G, Pagnon-Minot A, Marics I, Tattersall GJ, Moqrich A, Sigaudo-Roussel D.
J Invest Dermatol. 2018 Mar;138(3):688-696. doi: 10.1016/j.jid.2017.10.006. Epub 2017 Oct 17. PMID: 29054601


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


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


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


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


Heterogeneity in primary nociceptive neurons: from molecules to pathology.

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


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


  • P .Delmas, CRN2M Marseille
  • E. Bourinet, IGF Montpellier
  • Y. Lefeuvre, IINS Bordeaux
  • 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)










Members more

  Francis Castets Nadine Clerc Stéphane Gaillard Pascale Malapert Irène Marics Lucie Pepino Ana Reynders Sungjae Yoo
Aziz Moqrich
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Aziz Moqrich


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aude Charron

MSc student

Francis Castets
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Francis Castets


Nadine Clerc
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Nadine Clerc


Stéphane Gaillard
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Stéphane Gaillard


Pascale Malapert
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Pascale Malapert

Technical staff

Irène Marics
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Irène Marics

University lecturer

Lucie Pepino
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Lucie Pepino

PhD student

Ana Reynders
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Ana Reynders


Sungjae Yoo
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Sungjae Yoo

Postdoctoral fellow


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