Figure 9

Hypothesis for the development of tactile allodynia following nerve injury. TLR 2 and 4 are expressed on the surface membrane (solid outline), signal through the adapters TIRAP and MyD88 resulting NF-κB activation and proinflammatory cytokine expression such as TNF. Alternatively, TLR4 can signal through adaptors TRAM and TRIF. TLR3 is expressed in the endosome (dotted outline) and signals through TRIF. TRIF can activate IRF3 and initiate IFNβ transcription. We hypothesize that there is an initial endogenous TLR activation signal following nerve injury that results in: i) concurrent activation of multiple TLRs; ii) the TLR2 and TLR4 TIRAP-MyD88 pathway and production of TNF produces an ipsilateral and contralateral tactile allodynia; and iii) the TLR3-TRIF pathway suppresses contralateral allodynia development associated with interferon release (dotted square) and downstream interferon receptor signaling.