ATP receptors gate microglia signaling in neuropathic pain

  • Trang T
  • Beggs S
  • Salter M
  • 95

    Readers

    Mendeley users who have this article in their library.
  • 60

    Citations

    Citations of this article.

Abstract

Microglia were described by Pio del Rio-Hortega (1932) as being the 'third element' distinct from neurons and astrocytes. Decades after this observation, the function and even the very existence of microglia as a distinct cell type were topics of intense debate and conjecture. However, considerable advances have been made towards understanding the neurobiology of microglia resulting in a radical shift in our view of them as being passive bystanders that have solely immune and supportive roles, to being active principal players that contribute to central nervous system pathologies caused by disease or following injury. Converging lines of evidence implicate microglia as being essential in the pathogenesis of neuropathic pain, a debilitating chronic pain condition that can occur after peripheral nerve damage caused by disease, infection, or physical injury. A key molecule that modulates microglial activity is ATP, an endogenous ligand of the P2-purinoceptor family consisting of P2X ionotropic and P2Y metabotropic receptors. Microglia express several P2 receptor subtypes, and of these the P2X4, P2X7, and P2Y12 receptor subtypes have been implicated in neuropathic pain. The P2X4 receptor has emerged as the core microglia-neuron signaling pathway: activation of this receptor causes release of brain-derived neurotrophic factor (BDNF) which causes disinhibition of pain-transmission neurons in spinal lamina I. The present review highlights recent advances in understanding the signaling and regulation of P2 receptors expressed in microglia and the implications for microglia-neuron interactions for the management of neuropathic pain. © 2011 Elsevier Inc.

Author-supplied keywords

  • ATP
  • BDNF
  • Microglia
  • Nerve injury
  • Neuropathic pain
  • P2 purinoceptors
  • Spinal cord

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text

Authors

  • Tuan Trang

  • Simon Beggs

  • Michael W. Salter

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free