Fig. 9.

Cellular and molecular events contributing to TRPA1-mediated mechanical allodynia and neuroinflammation in a neuropathic pain model. Partial sciatic nerve ligation (pSNL) by releasing CCL2 (a) promotes the extravasation of hematogenous monocytes (b) that, via their rapid NOX2-dependent oxidative burst (red dots) target the TRPA1 channel localized in Schwann cells (c). TRPA1 activation in Schwann cells evokes a Ca²⁺-dependent, NOX1-mediated (d) prolonged H₂O₂ (green dots) generation (e) with a dual function. The outward H₂O₂ release (f) produces a space-scaled gradient that determines the final macrophage influx to the injured nerve trunk, whereas the inward H₂O₂ release (g) targets nociceptor TRPA1 to produce mechanical allodynia (h). ROS reactive oxygen species