Modulation of TRPV1, nociceptor sensitization , and induction of thermal hyperalgesia by C-type natriuretic peptide

摘要: Rheumatoid arthritis (RA) is caused by aberrant attack of the joints native inflammatory system. This can lead to joint destruction and pain that be debilitating. Increased angiogenesis innervation nociceptive afferent fibers are characteristic features RA joints, which in addition elevated levels a wide variety mediators, thought play an important role pathogenesis chronic associated with RA. Interestingly, recent report indicates C-type natriuretic peptide (CNP) increased blood serum patients. Natriuretic peptides (NPs) control natriuresis normalize changes pressure. Many biological effects NPs mediated guanylate cyclase (GC)-coupled NP receptors, NPR-A NPR-B, whereas third receptor, NPR-C, lacks GC kinase domain acts as clearance receptor. In addition, NPR-C couple specific Gαi-βγ-mediated intracellular signaling cascades numerous cell types. Recent studies suggest also involved regulation sensitivity, although underlying mechanisms remain largely unknown. Aim 1, I show CNP acutely sensitized excitation mouse dorsal root ganglia (DRG) sensory neurons dependent on transient receptor potential vanilloid-1 (TRPV1). potentiated capsaicinand proton-activated TRPV1 currents cultured DRG neuronal firing frequency, effect was absent from mice. Further, injection into hind paw led development thermal hyperalgesia, 2, dissected mechanism sensitization CNP. My results all 3 functional NPRs expressed neurons;