Central mechanisms of pain sensitization
Mécanisme central de la sensibilisation à la douleur

IINS



English version

The aim of our project is to elucidate basic mechanisms responsible for cellular and network dysfunctions in rodent models of chronic inflammatory and neuropathic pain. We are particularly interested in the overlapping circuits that underlie both chronic pain and associated comorbidities, e.g. anxiety, ADHD, neurodegenerative diseases. Our hypothesis is that these comorbidities play a crucial role in maintaining chronic pain states by disrupting calcium-dependent sensory integration in the dorsal horn of the spinal cord through the modulation of brain to spinal cord descending pathways. Our focus is on peptidergic, serotoninergic, and miRNA-based mechanisms that influence descending controls and their spinal effects.

To address this question, we develop innovative methodologies to:

  • modulate and assess pain behaviour (conditional transgenesis, local infusion of pharmacological drugs and behavioural testing),
  • record spinal neurons (in vivo extracellular or patch-clamp recording),
  • characterize spinal neurons (Patch-Seq, exosome purification and transcriptomic analysis, high resolution 3D neuronal reconstruction),
  • modulate brain to spinal cord pathways (optogenetics).

Keys Publications

  • Radwani, H., Lopez‐Gonzalez, M. J., Cattaert, D., Roca‐Lapirot, O., Dobremez, E., Eiríksdóttir, E., … & Fossat, P. (2016). Cav1. 2 and Cav1. 3 l‐type calcium channels independently control short‐and long‐term sensitization to pain. The Journal of physiology. J Physiol. 15;594(22):6607-6626.
  • Letellier, M., Elramah, S., Mondin, M., Soula, A., Penn, A., Choquet, D., Landry, M., Thoumine, O., and Favereaux, A. 2014. MicroRNA miR-92a regulates translation and synaptic incorporation of GluA1 containing AMPA receptors during homeostatic scaling. Nat Neurosci 17(8):1040-2.
  • Dolique, T., Favereaux, A., Roca-Lapirot, O., Roques, V., Leger, C., Landry, M., and Nagy, F. (2013). Unexpected association of the « inhibitory » neuroligin 2 with excitatory PSD95 in neuropathic pain. Pain 154, 2529-2546.
  • Laffray, S., Bouali-Benazzouz, R., Papon, M.A., Favereaux, A., Jiang, Y., Holm, T., Spriet, C., Desbarats, P., Fossat, P., Le Feuvre, Y., Decossas, M., Heliot, L., Langel, U., Nagy, F., and Landry, M., (2012). Impairment of GABAB receptor dimer by endogenous 14-3-3zeta in chronic pain conditions. Embo J 31, 3239-3251.
  • Favereaux, A., Thoumine, O., Bouali-Benazzouz, R., Roques, V., Papon, M.A., Salam, S.A., Drutel, G., Leger, C., Calas, A., Nagy, F., and Landry, M. (2011). Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain. Embo J 30, 3830-3841.
  • Fossat, P., Dobremez, E., Bouali-Benazzouz, R., Favereaux, A., Bertrand, S.S., Kilk, K., Leger, C., Cazalets, J.R., Langel, U., Landry, M., and Nagy, F. (2010). Knockdown of L calcium channel subtypes: differential effects in neuropathic pain. J Neurosci 30, 1073-1085.


Chef(s) d'équipe

Membres de l'équipe



Personnel(s) de recherche

Alexandre Favereaux (Enseignant-chercheur)
André Calas
Christel Baudet (Enseignant-chercheur)
Pascal Fossat (Enseignant-chercheur)
Yves Le Feuvre (Chercheur)


Personnel(s) technique

Rabia Benazzouz


Post-doctorant(s)


Doctorant(s)

Cynthia Alkhoury Abboud
Joao Guerreiro Covita
Franck Aby
Yadaly Gassama