Grant: Operating Grant

Neuropathic pain is a prevalent condition for which no effective treatment is available. For decades, pain has been viewed as being mediated solely by nerve cells. However this view has been challenged by highlighting the active participation of other type of cells, called "Glia" in the initiation and/or maintenance of this hypersensitivity in different pathological conditions. Microglia and astrocytes are two major types of glial cells in the central nervous system. While ample evidence support the role of microglia in the regulation of chronic pain, much less is known about the importance of astrocytes. In this proposal I will focus on the involvement of this specific type of glial cells in the pathogenesis of neuropathic pain. Our previous studies revealed that nerve injury activated both microglia and astrocytes within the spinal cord and this glial cell activation is characterized by an early, transient response of microglia, followed by a late, persistent astrocyte activation. I will use pharmacological and molecular tools to disrupt locally astrocyte activation within the spinal cord to verify whether the astrocyte activation is necessary and to what extent it is important for the maintenance and the progression of the disease. Then I will investigate the mechanisms by which astrocytes modulate pain signal processing by targeting a specific protein located on astrocytes-Cx43 gap junction hemichannels. I will also examine the relationship of microglia and astrocyte activation to see whether early microglial activation is necessary for the subsequent astrocyte activation and what is (are) the signalling molecules involved in the crosstalk between two types of glial cells. Elucidating how spinal cord glia interact with nociceptive processing will advance our understanding on the etiology of chronic pain. Identification of new strategies and targets involved in neuropathic pain is likely to open new avenues to effective treatment of chronic pain.