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Central Mechanisms of Pain Sensitization

Central Mechanisms of Pain Sensitization
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Project Summary

Chronic pain relies on maladaptive plasticity that induces neuronal sensitization in dorsal spinal networks. The aim of our project is to shed light on basic mechanisms responsible for cellular, and network dysfunctions in the dorsal spinal cord of rodent models of neuropathic pain.
We develop 5 main research axes:


1/ The first line of research explore the role of intrinsic properties in the sensitization of spinal neurons.

  • We study how L-channels control the dynamics of nociceptive receptive fields by using in vivo patch-clamp.
  • We also develop an in-vivo-based HIFU approach to decipher L-channel properties through specific gene deletion.

2/ We investigate how GABAB inhibition of calcium-dependent intrinsic properties of dorsal horn neurons is hampered in neuropathic conditions by the association of the receptor with various partner proteins. Those interacting proteins impair GABAB inhibition through specific, distinct molecular mechanisms.

3/ We study the novel microRNA-based regulatory mechanisms in central sensitization to pain.

4/ We Study the role of peculiar C-LTMR sensory fiber in normal and pathological nociceptive transmission.

5/ Finally, we develop an in-vivo approach to study the role of neuropeptide in the descending control of nociceptive transmission in the dorsal horn of the spinal cord.

6 Keys Publications

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.