Bidirectional modulation between infiltrating CD3+ T-lymphocytes and astrocytes in the spinal cord drives the development of allodynia in monoarthritic rats

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.

Bone marrow-derived mesenchymal stem/stromal cells reverse the sensorial diabetic neuropathy via modulation of spinal neuroinflammatory cascades

“…The area of the ipsilateral superficial spinal dorsal horn was also calculated. The ratio of the above areas was used as the percentage area density of Iba1, GFAP, or gal-3 [ 38 ].…”

Epigenetic and miRNA Expression Changes in People with Pain: A Systematic Review

“…Lymphocytes from the bloodstream infiltrate into the central nervous system in models of peripheral inflammation and influence nociceptive and neuroimmune mechanisms. 88 Moreover, a number of miRNAs are involved in controlling the permeability of the bloodbrain barrier, 1 thus possibly making easier for molecules from peripheral tissues to enter and influence the central nervous system. In addition, when studies assessed clinical symptoms, many of them failed to detect significant correlations between dysregulated miRNAs and symptoms reported by patients.…”

Effects of diet on immune cells within the central nervous system

“…Recently, the role of T cell infiltration in a model of inflammatory pain was investigated. Flow cytometry revealed an increase in spinal cord-infiltrating T cells following an inflammatory injury (40). Together, these studies indicate a clear role for T cell infiltration in the development of various types of pain.…”