Abstract
Pain on the body surface can accompany disorders in the deep tissue or internal organs. However, the anatomical and physiological mechanisms are obscure. Here, we provided direct evidence of axon bifurcation in primary C-nociceptive neurons that innervate both the skin and a visceral organ. Double-labeled dorsal root ganglion (DRG) neurons and Evans blue extravasation were observed in 3 types of chemically-induced visceral inflammation (colitis, urocystitis, and acute gastritis) rat models. In the colitis model, mechanical hypersensitivity and spontaneous activity were recorded in vivo from double-labeled C-nociceptive neurons in S1 or L6 DRGs. These neurons showed significantly enhanced responses to both somatic stimulation and colorectal distension. Our findings suggest that the branching of C-nociceptor axons contribute to cutaneous hypersensitivity in visceral inflammation. Cutaneous hypersensitivity on certain locations of the body surface might serve as an indicator of pathological conditions in the corresponding visceral organ.
Highlights
Visceral pain, involving thoracic, abdominal, and pelvic organs, is the most common type of chronic pain nowadays [1,2,3]
We provide direct evidence that the double-labeled dorsal root ganglion (DRG) neurons innervate both the visceral organs and skin, and used in vivo electrophysiology and Evans blue extravasation to confirm that cutaneous hypersensitivity can be used as an indicator of visceral inflammation via C-nociceptive sensory axon bifurcation
DRG neurons were double-labeled by injecting the fluorescent dye DiI into visceral organs and CTB-488 into the corresponding skin
Summary
Visceral pain, involving thoracic, abdominal, and pelvic organs, is the most common type of chronic pain nowadays [1,2,3]. It is well recognized that visceral innervation is complex. Organs in the thoracic and abdominal cavities may be innervated by both the vagal and spinal nerves with central terminals in the brainstem and spinal cord, respectively. Some pelvic organs are innervated by the pelvic nerves, which terminate in the lumbosacral spinal cord [4, 5]. Unlike cutaneous pain that is well localized, visceral pain is diffuse and often referred to a distal superficial location [4, 6]. It is necessary to find an indicator to help detect and locate visceral pain in order to treat visceral diseases better
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