Figure 4.

Posttranslational changes in transduction mechanisms/ion channels at nociceptor peripheral terminals induced by inflammatory mediators increases sensitivity and reduces threshold (peripheral sensitization), which occurs as a result of changes in the transducer proteins themselves (e.g., VR1) and as a result of a PKC- and PKA-mediated phosphorylation of TTXr sodium channels. Both activity and retrograde transport of signal molecules can also induce transcriptional changes in the DRG, which increase transducer molecules (VR1), ion channels (SNS/SNS2), and synaptic neuromodulators (BDNF/substance P) both altering phenotype and potentiating the system.