Figure 1.

Blood–spinal cord barrier disruption and immune cell infiltration into the spinal cord as an underlying mechanism of neuropathic pain. (A) One downstream effect of treatment with chemotherapy agents such as vincristine (VCR) is the activation of endothelial cells of the BSCB and disruption of tight junctions. (B) CCR₂⁺ monocytes infiltrate into the spinal cord in response to the release of CCL₂ from endothelial cells. (B) Monocytes/macrophages release CatS, which cleaves neuronally expressed fractalkine (FKN) producing soluble fractalkine (sFKN). (D) sFKN activates CX₃CR₁ receptors on microglia, which in turn release pronociceptive mediators. (E) After chronic constriction injury (CCI) there is evidence for BSCB disruption. (F) One outcome of such disruption is that CXCR₃-expressing T-cells infiltrate into the spinal cord.