TY - JOUR
T1 - T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity
AU - Costigan, Michael
AU - Moss, Andrew
AU - Latremoliere, Alban
AU - Johnston, Caroline
AU - Verma-Gandhu, Monica
AU - Herbert, Teri A.
AU - Barrett, Lee
AU - Brenner, Gary J.
AU - Vardeh, Daniel
AU - Woolf, Clifford J.
AU - Fitzgerald, Maria
PY - 2009/11/18
Y1 - 2009/11/18
N2 - 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-γ (IFNγ), is upregulated in the dorsal horn after nerve injury in the adult but not neonate, and we show that IFNγ 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.
AB - 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-γ (IFNγ), is upregulated in the dorsal horn after nerve injury in the adult but not neonate, and we show that IFNγ 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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U2 - 10.1523/JNEUROSCI.4569-09.2009
DO - 10.1523/JNEUROSCI.4569-09.2009
M3 - Article
C2 - 19923276
AN - SCOPUS:70949108323
SN - 0270-6474
VL - 29
SP - 14415
EP - 14422
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 46
ER -