Role of neurogenic inflammation in local communication in the visceral mucosa

Abstract

Intense research has focused on the involvement of the nervous system in regard to cellular mechanisms underlying neurogenic inflammation in the pelvic viscera. Evidence supports the neural release of inflammatory factors, trophic factors, and neuropeptides in the initiation of inflammation. However, more recently, non-neuronal cells including epithelia, endothelial, mast cells, and paraneurons are likely important participants in nervous system functions. For example, the urinary bladder urothelial cells are emerging as key elements in the detection and transmission of both physiological and nociceptive stimuli in the lower urinary tract. There is mounting evidence that these cells are involved in sensory mechanisms and can release mediators. Further, localization of afferent nerves next to the urothelium suggests these cells may be targets for transmitters released from bladder nerves and that chemicals released by urothelial cells may alter afferent excitability. Modifications of this type of communication in a number of pathological conditions can result in altered release of epithelial-derived mediators, which can activate local sensory nerves. Taken together, these and other findings highlighted in this review suggest that neurogenic inflammation involves complex anatomical and physiological interactions among a number of cell types in the bladder wall. The specific factors and pathways that mediate inflammatory responses in both acute and chronic conditions are not well understood and need to be further examined. Elucidation of mechanisms impacting on these pathways may provide insights into the pathology of various types of disorders involving the pelvic viscera.

Ba‐Wei‐Die‐Huang‐Wan (Hachimi‐jio‐gan) can ameliorate ketamine‐induced cystitis by modulating neuroreceptors, inflammatory mediators, and fibrogenesis in a rat model

“…In observing the report from a KIC patient having a urachal cyst, the direct exposure of urinary ketamine and its metabolites play a crucial role in causing urothelial ulceration (eg, damaged uroplakin III membrane) of KIC. The hypothetic mechanisms of KIC from direct toxic effect suggest that the urothelium injured by chemicals would facilitate urinary toxic substances to penetrate through the bladder mucosa; thus, it may elicit an immune response and activate neurogenic inflammation by releasing inflammatory peptides (eg, substance P) from afferent neurons . Furthermore, during chronic persistent inflammation, TGF‐β1 may activate fibrogenesis and contribute to bladder interstitial fibrosis …”

“…Meanwhile, we observed the inhibition of central sensitization, as observed through fMRI in the PAG area as well as improved bladder overactivity in the ketamine/BWDHW group. The urothelium/mucosa functions not only as a barrier against urea and ion diffusion but also as a sensor that helps to control bladder function and dysfunction . Activation of TRPV1 receptors in terminal C‐fibers on the bladder mucosa produces a biphasic response.…”

“…KIC from direct toxic effect suggest that the urothelium injured by chemicals would facilitate urinary toxic substances to penetrate through the bladder mucosa; thus, it may elicit an immune response and activate neurogenic inflammation by releasing inflammatory peptides (eg, substance P) from afferent neurons. 23 Furthermore, during chronic persistent inflammation, TGF-β1 may activate fibrogenesis and contribute to bladder interstitial fibrosis. 24 BWDHW may modulate micturition behavior and aberrant bladder neurotransmission in ketamine-treated rats.…”

“…The urothelium/mucosa functions not only as a barrier against urea and ion diffusion but also as a sensor that helps to control bladder function and dysfunction. 23 Activation of TRPV1 receptors in terminal C-fibers on the bladder mucosa produces a biphasic response. The immediate effect is the generation of nociceptive impulses transmitted to the central nervous system and a peripheral release from the receptor terminals of substance P. The release of substance P and other neuropeptides would lead to detrusor contraction and neurogenic inflammation.…”

Complexity of systems and actions underlying neurogenic inflammation

“…skin and muscle. Such linkages are reviewed in the articles by Choi and DiNardo [19], Birder and Kullman [20] and Feuilloley [21]. An interesting variant on this theme is that afferent axon collaterals also project into the DRG.…”