Cutaneous hypersensitivity as an indicator of visceral inflammation via C-nociceptor's axon bifurcation

Pain on the body surface might accompany disorders in the deep tissue or internal organ.However,the anatomical and physiological mechanism is obscure.Here,we provided direct evidences of axon bifurcation in primary C-nociceptive neurons that innervate both the skin and a visceral organ.Double-labeled dorsal root ganglion(RG)neurons and Evans blue extravasation were observed in 3 types of chemo-induced visceral inflammation(colitis,urocystitis and acute gastritis)rat models.In the rat model of colitis,mechanical hypersensitivity and spontaneous activities were recorded in vivo from double-labeled C nociceptive neurons in S1 or L6 DRG.These neurons showed significantly enhanced responses to both somatic stimulation and colorectal distension.Our findings suggest that axon branching of C-noceptors may contribute to cutaneous hypersensitivity in visceral inflammation.Cutaneous hypersensitivity on certain locations of body surface might serve as an indicator of pathological conditions in the corresponding visceral organ.