BACKGROUND: The role of immune activation in Functional Dyspepsia (FD) patients without previous infection is unclear. We compare the gastric and circulating brain-derived neurotropic factor (BDNF), receptor potential vanilloid type (TRPV) families and various cytokines in FD patients. METHODS: Consecutive adult FD patients (Rome III) with no recent history of gastroenteritis and asymptomatic healthy controls were recruited for upper endoscopy. Subjects with GERD and IBS as predominant symptoms, diabetes mellitus, current or previous Helicobacter pylori infection, psychiatric illness and recent use of NSAID or PPI were excluded. Corpus biopsies and serum samples were collected. KEY RESULTS: Forty three [M:F=8:35, mean age: 35.0 (9.3)] FD patients were compared with 23 healthy controls [M:F=8:15, mean age: 36.6 (10.2)]. FD patients had postprandial distress syndrome (PDS) as predominant sub-type (PDS: 36, EPS: 2). There was no significant difference in the median inflammation score (FD:0 (0-1) vs Control:0 (0-1), P=.79). However, FD patients had significantly higher mRNA expression of TRPV1 (FD:0.014±0.007, Control:0.003±0.001, 4.6 fold, P=.02) and TRPV2 (FD:0.012±0.006, Control:0.003±0.001, 4 fold, P=.02) compared to controls. The serum (FD:258.0±12.3 ng ml , Control:319.7±18.1 ng ml , P<.01) and gastric BDNF mRNA (FD:0.06±0.008, Control:0.092±0.01, 0.65 fold, P=.02)levels significantly lower in FD patients. Secretion of cytokines (IL-4, IL-5, IL-6, IL-8, IL-10, G-CSF, TGF-β2, MCP-1)was also highly correlated with dyspeptic symptoms in patients with FD. CONCLUSIONS & INFERENCES: Despite lacking gastric mucosal inflammation, up-regulation of TRPV1 and TRPV2, down-regulation of BDNF were observed in FD patients. These suggest that immune alteration may contribute to the pathogenesis of FD without any previous infection.