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Role of neurosteroids in a novel mechanism modulating the nociceptive system through ATP and GABA receptors


Nociceptive stimuli are essential in maintaining the integrity of an organism. Certain diseases however generate chronic, pathological pain, which is detrimental to this integrity. P2X ATP receptors are involved in the initiation and transmission of nociceptive signals in peripheral tissues. The host laboratory showed that P2X receptors, as well as GABAA receptors, are involved in a new mechanism modulating nociceptive signals in the spinal cord and that their function can be affected by neurosteroids, a class of steroids produced in the nervous system.

This project aims to
(1) Determine the exact nature of the endogenous neurosteroids involved in nociception and their site of production
(2) Define both the acute and chronic action of these neurosteroids on nociceptive neurotransmission
(3) Determine the nociceptive neuronal subpopulations affected by these neurosteroids
(4) Evaluate the role of neurosteroids in the generation of pathological pain in disease states

We will use a multidisciplinary approach including morphological, electrophysiological and molecular methods applied to in vitro and in vivo models of inflammatory or Neutrogena pain. The results of this project will improve our comprehension of the generation of pathological pain and define the role of neurosteroids in the initiation and maintenance of pain. The neurosteroid modulation mechanism of nociceptive signalling will provide targets for new and innovative therapeutic strategies of chronic pathological pain management that avoid side effects such as addiction and tolerance. This project relies on the synergy of the competences of both the fellow and the host laboratory. It will result in a two-way knowledge transfer that will enhance both the career prospects of the fellow and the scientific excellence of the host institution and more generally of the European scientific community. The new concepts developed will provide new opportunities for European pharmaceutical industries.

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