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Plasticity of spinal inhibition in chronic pain

Research unit

UPR 3212 - Institut des Neurosciences Cellulaires et Intégratives (INCI)
5, rue Blaise Pascal, 67084 STRASBOURG

Group

Name: signalisation nociceptive dans la moelle epiniere

Group leader: SCHLICHTER Rémy - schlichter@inci-cnrs.unistra.fr

Group leader's phone: 03.88.45.66.65

Group organization:
- Chercheurs: 5
- ITA: 2
- Doctorants: 3
- Post-Docs: 0
- Autres: 1

Publications of the team linked to the topic (3 last years):
1) Inquimbert P, Moll M, Kohno T, Scholz J (2013) Stereotaxic injection of a viral vector for conditional gene manipulation in the mouse spinal cord. J Vis Exp 18 (73) e50313, doi:10.3791/50313.
2) Seibt F, Schlichter R (2015) Noradrenaline-mediated facilitation of inhibitory synaptic transmission in the dorsal horn of the rat spinal cord involves interlaminar communications. Eur J Neurosci 42:2654-2665.
3) Medrano MC, Dhanasobhon D, Yalcin I, Schlichter R, Cordero-Erausquin M (2016) Loss of inhibitory tone on spinal cord dorsal horn spontaneously and non-spontaneously active neurons in a mouse model of neuropathic pain. Pain (In press).

About PhD

PhD Director: SCHLICHTER Rémy - schlichter@inci-cnrs.unistra.fr

Phone: 03.88.45.66.65

Junior advisor: INQUIMBERT Perrine

Co-tutely: non

Co-Director: non

About PhD topic :

Title: Plasticity of spinal inhibition in chronic pain

Project: Pain is an unpleasant sensory and emotional experience, but is essential to detect and avoid stimulation possibly damageable for our body. However, in some circumstances, such as a nerve injury, pain may lose its protective function. This pathological pain, so called neuropathic pain are characterized by hyperalgesia (a painful stimulus becomes more painful) and allodynia (an innocuous stimulus becomes painful), and usually persists even after a complete recovery from the injury. Unfortunately, current available treatments provide only partial relief.

Nociceptive fibers originating from peripheral sensory neurons convey nociceptive information to the dorsal horn (DH) where networks of interneurones are modulating and filtering this sensory information prior to its transmission to supraspinal centers. It is only while reaching the cerebral cortex that this information is interpreted as pain. The spinal integration of nociceptive information involves a local neural network of excitatory and inhibitory interneurons.
Inhibitory synaptic transmission mediated by GABA and Glycine is central to the integration of nociceptive messages in the DH. Following, peripheral nerve injury, plastic changes occur in the DH network. Among these, an impaired inhibitory synaptic transmission in the DH may contribute to neuropathic pain. Indeed, a pharmacological blockade of inhibition in healthy animals DH mimics symptoms of neuropathic pain.
Furthermore, following a nerve injury, primary sensory neurons develop an abnormal spontaneous activity leading to the recruitment of NMDA receptor in DH. NMDA receptors are well known to be critically involved in neuropathic pain state and in plastic changes in neuronal networks (LTP, LTD,…). However, implication of these receptors in the plastic changes of inhibitory synaptic transmission in the DH is still unknown.
The aim of the proposed thesis project is to study the involvement of NMDA receptors in the plastic changes of the synaptic inhibition in the DH inhibition following a peripheral nerve injury. This study will involve electrophysiological recordings (patchclamp on spinal cord slices) associated with behavioral and immunohistochemistry approaches. The expected results will allow a better understanding of mechanisms involved in the plasticity of spinal inhibition underlying the development and maintenance of neuropathic pain.

Wished skills: Good basis in neurosciences (membrane permeability, ionic channels, synaptic transmission, neurones networks, sensorial neurophysiology).
Interest for the study of synaptic transmission and its modulation
High degree of motivation, interest for multidisciplinary experimental approaches.
Human qualities required for teamwork

Expertises which will be acquired during the training: Patch-clamp techniques on spinal cord slices
Immunocytochemistry
Behavioral testing of sensory threshold
Viral transfection and intraspinal injections
Analysis of electrophysiological
Analysis of a scientific problem from a molecular to an integrated level.