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Purinoceptors in microglia and neuropathic pain

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Abstract

Emerging evidence indicates that microglia play a critical role 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. Microglia are immunocompetent cells of the central nervous system and express various ionotropic P2X and metabotropic P2Y purinoceptors. After injury to a peripheral nerve, microglia in the spinal cord become activated and upregulate expression of the P2X4 receptor. Recent findings suggest that activation of P2X4 receptors evokes release of brain-derived neurotrophic factor from microglia and that this mediates microglia–neuron signaling leading to pain hypersensitivity. Thus, P2X4 receptors and the intracellular signaling mediators in microglia are promising therapeutic targets for the development of novel pharmacological agents in the management of neuropathic pain.

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Acknowledgements

The work of the authors is supported by grants from the Canadian Institutes of Health Research and from the Brain Repair Program of Neuroscience Canada. M. W. Salter holds a Canada Research Chair (Tier I) in Neuroplasticity and Pain.

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  1. University of Toronto Centre for the Study of Pain, Programmes in Brain and Behaviour and Cell Biology, Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada

    Tuan Trang, Simon Beggs & Michael W. Salter

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  1. Tuan Trang
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Correspondence to Michael W. Salter.

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Trang, T., Beggs, S. & Salter, M.W. Purinoceptors in microglia and neuropathic pain . Pflugers Arch - Eur J Physiol 452, 645–652 (2006). https://doi.org/10.1007/s00424-006-0074-5

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