Neurokinin-1 (NK-1) receptor is required in antigen-induced cystitis

Interstitial cystitis (IC) is a debilitating disease that has been adversel y affecting the quality of women's lives for many years. The trigger in IC is not entirely known, and a role for the sensory nerves in its pathogenesi s has been suggested. In addition to inflammation, increased mast cell numb ers in the detrusor muscle have been reported in a subset of IC patients. E xperimentally, several lines of evidence support a central role for substan ce P and neurokinin-1 (NK-1) receptors in cystitis. The availability of mic e genetically deficient in neurokinin-1 receptor (NK-1R(-/-)) allows us to directly evaluate the importance of substance P in cystitis, An unexpected finding of this investigation is that NK-1R(-/-) mice present increased num bers of mast cells in the bladder when compared with wild-type control mice . Despite the increase in mast cell numbers, no concomitant inflammation wa s observed, In addition, bladder instillation of mild-type mice with a sens itizing antigen induces activation of mast cells and an acute inflammatory response characterized by plasma extravasation, edema, and migration of neu trophils. Antigen-sensitized NK-1R(-/-) mice also exhibit bladder mast cell degranulation in response to antigen challenge. However, NK-1R(-/-) mice a re protected from inflammation, failing to present bladder inflammatory cel l infiltrate or edema in response to antigen challenge. This work presents the first evidence of participation of NK-1 receptors in cystitis and a man datory participation of these receptors on the chain of events linking mast cell degranulation and inflammation.