Figure 8.

Potential BDNF-dependent and BDNF-independent mechanisms of pain in uninjured and injured spinal cord. (a) In the absence of SCI, BDNF-mediated effects contribute to pain. Constitutive increases in BDNF and TrkB expression activate MAPK/ERK and PLC-PKC kinase pathways, which in turn leads to transcription of pain genes and posttranslational modifications (e.g., phosphorylation of glutamate receptors). (b) In the acute stage of SCI, both BDNF and TrkB levels are decreased in the spinal cord dorsal horn [93]. However, during this stage, MAPK/ERK pathways could be activated by BDNF-independent mechanisms, presumably an alternate pathway such as the TNFα pathway (both TNFα and TNR1 expressions are upregulated by SCI [94]). A decrease in KCC2 by SCI which alters GABA-mediated chloride function is likely to also contribute to pain after SCI. (c) During the chronic stage of injury, pERK levels are increased [94, 95], which may result from increases in both BDNF-TrkB signaling and TNFα-TNFR signaling. Activation of these pathways could consequently increase kinase activity and the transition of pain genes. Overall, we propose that although BDNF may not necessarily initiate pain-producing pathway after SCI, it is likely to contribute to pain hypersensitivity during the chronic stages of injury.