CCL2 is a key mediator of microglia activation in neuropathic pain states

Authors

  • Michael A. Thacker,

    1. Neurorestoration group, Wolfson Centre for Age Related Diseases, Kings College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London, SE1 1UL, London, UK
    2. Academic Department of Physiotherapy, Kings College London, London, UK
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  • Anna K. Clark,

    1. Neurorestoration group, Wolfson Centre for Age Related Diseases, Kings College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London, SE1 1UL, London, UK
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  • Thomas Bishop,

    1. Neurorestoration group, Wolfson Centre for Age Related Diseases, Kings College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London, SE1 1UL, London, UK
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  • John Grist,

    1. Neurorestoration group, Wolfson Centre for Age Related Diseases, Kings College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London, SE1 1UL, London, UK
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  • Ping K. Yip,

    1. Neurorestoration group, Wolfson Centre for Age Related Diseases, Kings College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London, SE1 1UL, London, UK
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  • Lawrence D.F. Moon,

    1. Neurorestoration group, Wolfson Centre for Age Related Diseases, Kings College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London, SE1 1UL, London, UK
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  • Stephen W.N. Thompson,

    1. Neurorestoration group, Wolfson Centre for Age Related Diseases, Kings College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London, SE1 1UL, London, UK
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    • Present Address: School of Biological Sciences, University of Plymouth, Plymouth, UK.

  • Fabien Marchand,

    1. Neurorestoration group, Wolfson Centre for Age Related Diseases, Kings College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London, SE1 1UL, London, UK
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  • Stephen B. McMahon

    Corresponding author
    1. Neurorestoration group, Wolfson Centre for Age Related Diseases, Kings College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London, SE1 1UL, London, UK
    2. The London Pain Consortium, UK
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Neurorestoration group, Wolfson Centre for Age Related Diseases, King's College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London, SE1 1UL, London, UK. Tel.: +44 2078486270; fax: +44 2078486165. Stephen.mcmahon@kcl.ac.uk

ABSTRACT

While neuroimmune interactions are increasingly recognized as important in nociceptive processing, the nature and functional significance of these interactions is not well defined. There are multiple reports that the activation of spinal microglia is a critical event in the generation of neuropathic pain behaviors but the mediators of this activation remain disputed. Here we show that the chemokine CCL2, produced by both damaged and undamaged primary sensory neurons in neuropathic pain states in rats, is released in an activity dependent manner from the central terminals of these fibres. We also demonstrate that intraspinal CCL2 in naïve rats leads to activation of spinal microglia and neuropathic pain-like behavior. An essential role for spinal CCL2 is demonstrated by the inhibition of neuropathic pain behavior and microglial activation by a specific neutralising antibody to CCL2 administered intrathecally. Thus, the neuronal expression of CCL2 provides a mechanism for immune activation, which in turn regulates the sensitivity of pain signaling systems in neuropathic pain states.

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