Fig. 9: Schematic representation of the pathway that signal prolonged cutaneous allodynia elicited by CGRP released and associated with neurogenic inflammation. | Nature Communications

Fig. 9: Schematic representation of the pathway that signal prolonged cutaneous allodynia elicited by CGRP released and associated with neurogenic inflammation.

From: Schwann cell endosome CGRP signals elicit periorbital mechanical allodynia in mice

Fig. 9: Schematic representation of the pathway that signal prolonged cutaneous allodynia elicited by CGRP released and associated with neurogenic inflammation.The alternative text for this image may have been generated using AI.

The pro-migraine neuropeptide, CGRP, released from trigeminal cutaneous afferents, activates CLR/RAMP1 on Schwann cells. CLR/RAMP1 traffics to endosomes, where sustained G protein signaling increases cAMP and stimulates PKA that results in nitric oxide synthase activation. The ensuing release of nitric oxide targets the oxidant-sensitive channel, TRPA1, in Schwann cells, which elicits persistent ROS generation. ROS triggers TRPA1 on adjacent C- (1) or Aδ-fiber (2) afferents resulting in periorbital allodynia, a hallmark of migraine pain. The inset shows several unmyelinated axons invaginated into a Schwann cell forming a Remak bundle.

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