Neurokinin 1 receptors (NK₁) play a fundamental role in neurogenic inflammation. We sought to determine the mechanisms downstream NK1 receptor activation using cDNA arrays and a novel statistical method to analyze gene-expression. We used female NK₁R^-/- and wild type (WT) mice that were sensitized actively by i.p. injections of DNP₄-human serum albumin. Cystitis was induced by intravesical instillation of antigen of DNP₄-ovalbumin and control mice were challenged with saline. One, four, and twenty-four hours after instillation, bladders were removed for: a) RNA extraction (n=3), b) replicate of RNA extraction (n=3), and c) and morphological analysis (n=6). For cDNA array experiments, three bladders from each group were homogenized and total RNA was obtained. DNase-treated RNA was reverse-transcribed to cDNA, labeled with [alpha-³²P]dATP and hybridized to AtlasTM Mouse 1.2 Arrays (Clontech). After calculating the mean and SD for background spots, each experimental value was assigned a normalized score S using the formula S[[rad]] = (S-Av)/SD, where S[[rad]] is the original pixel value, and Av and SD are the mean and standard deviation of background spots. Only genes expressed 3 SDs above background were used. Hyper-variable genes were sorted by cluster analysis. Matrices of correlation coefficients were calculated and represented in a connectivity mosaic. As results, we found that in wild-type (WT) mice the most prominent gene cluster had neprilysin in a central position and positively correlated to a group of activator protein-1 (AP-1) responsive genes, including: laminin alpha 3, tissue plasminogen activator 11, fos-B, and TNF-beta. In WT mice, antigen-induced bladder inflammation led to a down regulation in neprilysin expression. In contrast, NK₁R^-/- mice failed to mount an inflammatory reaction and presented NEP negatively correlated with the same genes described in WT. In conclusion, this work indicates an overriding participation of NK1R and neprilysin in bladder inflammation, provides a working model for the involvement of AP-1 transcription factor, and evokes testable hypotheses regarding the role of NK₁ receptors and neprilysin in inflammation.