ATP Receptors of Microglia Involved in Pain

  1. Derek J. Chadwick Organizer and
  2. Jamie Goode
  1. Kazuhide Inoue

Published Online: 7 OCT 2008

DOI: 10.1002/9780470032244.ch21

Purinergic Signalling in Neuron-Glia Interactions: Novartis Foundation Symposium 276

Purinergic Signalling in Neuron-Glia Interactions: Novartis Foundation Symposium 276

How to Cite

Inoue, K. (2006) ATP Receptors of Microglia Involved in Pain, in Purinergic Signalling in Neuron-Glia Interactions: Novartis Foundation Symposium 276 (eds D. J. Chadwick and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470032244.ch21

Author Information

  1. Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 21 APR 2006

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470018606

Online ISBN: 9780470032244

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Keywords:

  • ATP and mitogen-activated protein kinase (MAPK);
  • ATP receptor expression in microglia;
  • microglia and pain;
  • cytokines and neuropathic pain;
  • P2X7 receptor and human genome polymorphisms

Summary

Microglia, activated when physiological homeostasis is threatened, play an important role as immune cells in the CNS. Activated microglia show a progressive series of changes in morphology, gene expression, function and number, and produce and release various chemical mediators, including proinflammatory cytokines that can produce immunological actions and modify neuronal function. Recently, accumulating evidence has indicated an important role for ATP receptors of activated microglia in neuropathic pain. Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, cancer, diabetes or infection. The expression of the P2X4 receptor, a subtype of ATP receptors, is enhanced in spinal microglia in a peripheral nerve injury model, and blocking pharmacologically and suppressing molecularly P2X4 receptors produces a reduction of the neuropathic pain. Several cytokines such as interleukin 6 (IL6) and tumour necrosis factor α (TNFα) in the dorsal horn are also increased after nerve lesion and have been implicated in contributing to nerve-injury pain. ATP can activate mitogen-activated protein kinase (MAPK) leading to the release of bioactive substances including cytokines from microglia. Thus, diffusible factors released from activated microglia by the stimulation of purinergic receptors may have an important role in the development of neuropathic pain.