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The Journal of Neuroscience, November 18, 2009, 29(46):14415-14422; doi:10.1523/JNEUROSCI.4569-09.2009

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Neurobiology of Disease
T-Cell Infiltration and Signaling in the Adult Dorsal Spinal Cord Is a Major Contributor to Neuropathic Pain-Like Hypersensitivity

Michael Costigan,^3 * Andrew Moss,^1 * Alban Latremoliere,^3 * Caroline Johnston,² Monica Verma-Gandhu,³ Teri A. Herbert,³ Lee Barrett,³ Gary J. Brenner,³ Daniel Vardeh,³ Clifford J. Woolf,³ and Maria Fitzgerald¹

¹UCL Department of Neuroscience, Physiology & Pharmacology and ²UCL Department of Biochemistry, University College London, London WC1 EBT, United Kingdom, and ³Neural Plasticity Research Group, Massachusetts General Hospital, Charlestown, Massachusetts 02129

Correspondence should be addressed to either of the following: Michael Costigan, Neural Plasticity Research Group, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, Email: costigan{at}helix.mgh.harvard.edu; or Andrew Moss at his present address: Pain Biology, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK, Email: andrew.moss{at}pfizer.com

Partial peripheral nerve injury in adult rats results in neuropathic pain-like hypersensitivity, while that in neonatal rats does not, a phenomenon also observed in humans. We therefore compared gene expression profiles in the dorsal horn of adult and neonatal rats in response to the spared nerve injury (SNI) model of peripheral neuropathic pain. The 148 differentially regulated genes in adult, but not young, rat spinal cords indicate a greater microglial and T-cell response in adult than in young animals. T-cells show a large infiltration in the adult dorsal horn but not in the neonate after SNI. T-cell-deficient Rag1-null adult mice develop less neuropathic mechanical allodynia than controls, and central expression of cytokines involved in T-cell signaling exhibits large relative differences between young and adult animals after SNI. One such cytokine, interferon- (IFN), is upregulated in the dorsal horn after nerve injury in the adult but not neonate, and we show that IFN signaling is required for full expression of adult neuropathic hypersensitivity. These data reveal that T-cell infiltration and activation in the dorsal horn of the spinal cord following peripheral nerve injury contribute to the evolution of neuropathic pain-like hypersensitivity. The neuroimmune interaction following peripheral nerve injury has therefore a substantial adaptive immune component, which is absent or suppressed in the young CNS.

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Received Sept. 15, 2009; accepted Sept. 25, 2009.

Correspondence should be addressed to either of the following: Michael Costigan, Neural Plasticity Research Group, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, Email: costigan{at}helix.mgh.harvard.edu; or Andrew Moss at his present address: Pain Biology, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK, Email: andrew.moss{at}pfizer.com

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