Abstract
Increasing evidence suggests that T cells and glia participate in the process of neuropathic pain. However, little is known about the involvement of T cells or the interaction between glia and T cells at the molecular level. Here we investigated the phenotype of T cell infiltration into the spinal cord in inflammatory pain and explored potential crosstalk between glia and T cells. The establishment of monoarthritis produced T cell infiltration and astrocyte activation, exhibiting similar kinetics in the spinal cord. T-cell-deficient (Rag1−/−) mice significantly attenuated MA-induced mechanical allodynia and GFAP upregulation. Double immunofluorescence staining showed that CD3 mainly colocalized with interferon-gamma (IFN-γ). Western blot and flow cytometry showed that multiple intrathecal administrations of astrocytic inhibitor fluorocitrate decreased IFN-γ-production without decreasing T cell number in the spinal cord. Spinal IFN-γ blockade reduced MA-induced mechanical allodynia and astroglial activation. In contrast, treatment with rIFN-γ directly elicited persistent mechanical allodynia and upregulation of GFAP and pJNK1/2 in naïve rats. Furthermore, rIFN-γ upregulated the phosphorylation of NF-κB p65 in cultured astrocytes vitro and spinal dorsal horn vivo. The results suggest that Th1 cells and astrocytes maintain inflammatory pain and imply that there may be a positive feedback loop between these cells via IFN-γ.
Highlights
In clinical pathological pain, arthritic pain is a major health care burden
Flow cytometric analysis showed a significant increase in the number of spinal cord-infiltrating T cells on day 7, and the increase became more pronounced on day 10 after the inflammatory insult (One-way analysis of variance (ANOVA), F2,22 = 55.27, p < 0.001)
We examined whether T cell-mediated adaptive immune response was involved in the development of inflammatory pain
Summary
Arthritic pain is a major health care burden. Arthritis affects 1% of the worldwide population and initiates with inflammation of the synovium in peripheral joints, which progresses to destruction of articular cartilage, leading to significant joint degeneration, pain and loss of function[1,2]. Increasing evidence suggests that spinal cord-infiltrating T lymphocytes contributes to the development and maintenance of neuropathic pain[5,6,7]. Comparison of the microarray gene profiles of the spinal cord from neonate and adult animals 7 days post-spared nerve injury identified 148 differentially expressed genes. Most of these genes were related to immune function, and they included numerous genes involved in T-cell signaling[5]. We investigated the subtypes and functional roles of T cells infiltrating the spinal cord of rats with complete Freund’s adjuvant (CFA)-induced monoarthritis (MA), a model of inflammatory pain. We examined the molecular crosstalk between glia and T cells in the CNS after inflammatory insult
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