Introduction. TGFβ is upregulated in chronic inflammation and it has been associated with nociceptive sensitization in several somatic pain models. It is also a key factor in the pathogenesis of fibrosis in chronic pancreatitis and pancreatic cancer. We therefore hypothesized that increased levels of TGFb within the pancreas may result in pain through sensitization of pancreatic nociceptors in dorsal root ganglia (DRG). Methods. TGFβ1 was infused in different concentrations into the duct of adult male rats 3 weeks after injection of DiI into the pancreas to retrogradely label sensory neurons in pancreas-specific DRG. After 48 hours of TGFb infusion, pain behavior was assessed using a previously established paradigm of electrical stimulation of the pancreas. Then, thoracic T9-T13 DRGs were harvested and dissociated in culture. DiI labeled DRG single cells were patched for electrophysiological measurements. Results. Animals infused with TGFβ1 at a dose of 1 mg, but not 100 ng, displayed hypersensitivity to graded pancreatic electrical stimulation, with significantly more pain behaviors (Figure, P<001 by two-way ANOVA). Further, pancreas-specific DRG neurons displayed evidence of increased neural excitability in rats receiving 400 ng (a dose that is also associated with increased pain behavior) of intra-pancreatic TGFb1 as compared with rats receiving vehicle alone, as follows: resting membrane potential: -49.9±1.6 versus 57.2±3.9 mV (P=0.03); rheobase: 0.24±0.04 versus 0.38±0.01 nA (P=0.01); number of action potentials at 1x rheobase: 1.7±0.22 versus 1.1±0.08 (P=0.04) and 3.1±0.22 from 1.3±0.07 (P=0.001) at 2 x rheobase. A significant decrease was seen in transient 'A-type' current (IA) potassium currents (55.01 + 9.63; P=0.03) but not in 'sustained delayed rectifier type' (IK) currents. IA currents have been previously shown to be reduced in the pancreatic nociceptors in chronic pancreatitis. Conclusions. The results of this study are consistent with a role for TGFb in mediating pain and nociceptive sensitization in the pancreas. Infusion of TGFb mimics the behavioral and neurobiological changes that are characteristic of chronic pancreatitis. These results provide a novel therapeutic target for pain in pancreatic disorders where TGFb expression is prominent such as chronic pancreatitis and pancreatic cancer.