Figure 7.

Schematic model indicated that TLR4 expressed on Na_v1.8⁺ nociceptors in the lumbar DRGs (L3–5) plays an important role in regulating the localization of HMGB1 in response to neuropathic injury in females, but not males. This is both behaviorally and molecularly significant, as female mice lacking TLR4 expression on their Na_v1.8+ nociceptors exhibit reduced mechanical hypersensitivity following SNI. Moreover, re-expression of TLR4 only on these Na_v1.8 nociceptors recapitulates a behavioral phenotype similar to that of wild type mice. This effect is not present in male mice of either genotype.