Chronic pain is a devastating and widespread problem yet the existing treatments have limited long-term efficacy. Our research focuses on spinal cholinergic analgesia as a source of alternative therapy.
Spinal acetylcholine (ACh) is an important modulator of sensory processing, also implicated in the analgesic effects of clonidine and morphine. Our latest results have demonstrated that this ACh arises from a sparse population of dorsal horn cholinergic interneurons. Understanding how such a sparse population achieves a major control of nociceptive processing is an ambitious challenge that we address using a combination of neuroanatomy, behavioural experiments, electrophysiology and optogenetics.
By analogy with other populations of exceedingly rare but intensely connected neurons that serve as hubs or orchestral directors for large networks, our working hypothesis is that a unique positioning within the spinal network makes cholinergic neurons a keystone of sensory processing.
Our specific aims are to identify (i) the stimuli that trigger the release of ACh, (ii) the neurons that are pre- and postsynaptic to cholinergic interneurons, and (iii) the consequences of the stimulation of these neurons on the spinal sensory network.
The cholinergic modulation of nociceptive stimuli being deficient in a mouse model of chronic neuropathic pain, we will test the hypothesis that it is due to a functional uncoupling of cholinergic neurons from sensory fibers.
Pawlowski SA., Gaillard S., Ghorayeb I., Ribeiro-da-Silva A., Schlichter R., Cordero-Erausquin M. (2013), A novel population of cholinergic neurons in the macaque spinal dorsal horn of potential clinical relevance for pain therapy. J. Neurosci., 33 (9) : 727-37.
Mesnage B., Gaillard S., Godin A., Rodeau JL., Hammer M., von Engelhardt J., Wiseman P., De Koninck Y., Schlichter R., Cordero-Erausquin M. (2011) Morphological and functional characterization of cholinergic interneurons of the dorsal horn of the mouse spinal cord. J. Comp. Neurol., 519 (16) : 3139-58.
Yalcin I., Charlet A., Cordero-Erausquin M., Tessier L.H., Picciotto M., Schlichter R., Poisbeau P., Freund-Mercier MJ., Barrot M. (2011) Spinal β2-subunit-containing nicotinic acetylcholine receptors are critical for the control of nociceptive thresholds in mice. Pain, 152 (9) : 2131-7.
Cordero-Erausquin M., Allard S., Dolique T., Bachand K., Ribeiro-da-Silva A., De Koninck, Y. (2009) Dorsal horn neurons presynaptic to lamina I spino-parabrachial neurons revealed by transynaptic labelling. J. Comp. Neurol., 517 (5): 601-15.
2013-15 Strasbourg University, Institute of Advanced Studies Fellow
2006-8 Canadian Institutes of Health Research (CIHR) Post-doctoral Fellowship
2005 French Ministry of Post-graduate Studies & Research, Return of Post-docs
2004 CIHR, IALA/IMHA Best Poster Award, Montreal
2003-06 Fonds de la Recherche en Santé du Québec, Post-doctoral Fellowship
1998-02 French Ministry of Post-graduate Studies & Research, PhD fellowship
1995-8 French Ministry of Post-graduate Studies & Research B.Sc.& M.Sc. Scholarship (ENS)