Papers of the Week

Patients with urinary tract infections (UTIs) suffer from urinary frequency, urgency, dysuria, and suprapubic pain, but the mechanisms by which bladder afferents sense the presence of uropathogens and encode this information is not well understood. The calcitonin gene-related peptide (CGRP) is a 37-mer neuropeptide found in a subset of bladder afferents that terminate primarily in the lamina propria. Here we report that the CGRP receptor antagonist BIBN4096BS lessens lower urinary tract symptoms and prevents the development of pelvic allodynia in mice inoculated with uropathogenic (UPEC) without altering urine bacterial loads or the host immune response to the infection. These findings indicate that CGRP facilitates the processing of noxious/inflammatory stimuli during UPEC infection. Using fluorescent hybridization, we identify a population of suburothelial fibroblasts in the lamina propria, a region where afferent fibers containing CGRP terminate, that express the canonical CGRP receptor components and . We propose that these fibroblasts, in conjunction with CGRP afferents, form a circuit that senses substances released during the infection and transmit this noxious information to the central nervous system.