Working model of BDNF-trkB up-regulation in DRG during TNF-α-mediated inflammation and hyperalgesia. Upon inflammation, TNF-α may be released near nociceptors where it binds TNFR1 and undergoes retrograde transport to DRG via TNFR1. In the DRG, TNF-α enhances expression of BDNF, trkB, CGRP and TRPV1, through either transcriptional or translational regulation. The enhanced BDNF is released locally to act as an autocrine or paracrine signal on pre-synaptic trkB receptors in the DRG. Consequently, activated trkB receptor increases pain mediators, CGRP and/or substance P release and facilitates pain transmission, possibly via phospho-ERK1/2.