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Accueil > UMR 7242 Biotechnologie et signalisation cellulaire (Jean-Luc Galzi) > Récepteurs, protéines membranaires et innovation thérapeutique (Animation scientifique : Isabelle Schalk) > RCPG, douleur et inflammation (Frédéric Simonin) > Nos thématiques > Glia & chemokine in OIH & CPIH

Glia & chemokine in OIH & CPIH

Role of Glia and chemokines in hyperalgesia induced by opiates (OIH) and persistent pain (CPIH)

Although our understanding of pain sensitization and hyperalgesia has primarily revolved around neuronal mechanisms, it has been recognized that surrounding astrocytes and microglia are powerful modulators of pain. They are therefore emerging as new targets for drug development (Milligan and Watkins 2009). Under normal conditions, microglia cells function as resident macrophages of the CNS and as sentinels of injury and infection. Within hours following peripheral nerve injury, bone marrow-derived microglial cells accumulate into the spinal cord. This phenomenon is considered critical for the development of neuropathic pain. Activated microglial cells release a panoply of signaling molecules including cytokines and chemokines (Milligan and Watkins 2009), which enhance neuronal central sensitization and nerve injury-induced persistent pain (Watkins et al. 2007).

Thus, it appears that microglia activation is critical to trigger persistent pain conditions (Tsuda et al. 2003). Moreover, opioid agonists have been shown to activate glia presumably via direct stimulation toll-like receptor 4, a phenomenon which has been proposed to be responsible for adverse effects of opiates including OIH (Hutchinson et al. 2007). While inflammatory and neuropathic pain syndromes are considered distinct types of pain, emerging evidence suggests that the production of proinflammatory agents associated to the innate immune response participate to the development and maintenance of both inflammatory and neuropathic pain. Moreover, the role of the inflammatory response in the generation of pain is not limited to effects produced by the influx of leukocytes per se. Particularly, the release of chemokines by different cells in the central nervous system (neurons, astrocytes, microglial cells) has recently come to light as playing a central role in the induction of maintenance of chronic pain.
In this project, we focus on chemokines that have been proposed to play a role in the development of hyperalgesia including CCL2, CCL3, CCL5, CXCL10, CXCL12 and CX3CL1. We will either use or identify pharmacological tools as well as genetic tools to modulate their actions and determine their contribution in the two types of hyperalgesia that we study.

 

References :

Dauboeuf et al , 2011, Inflammation research 60, 112-113

Hutchinson et al, 2007, Scientific World Journal 7, 98-111

Milligan and Watkins, 2009, Nat Rev Neurosci 10, 23-36

Tsuda et al, 2003, Nature 424, 778-783

Watkins et al, 2007, Brain Res Rev 56, 148-169

 

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