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Integration and modulation of primary afferent sensory information begins at the first terminating sites within the CNS, where central inhibitory circuits play an integral role. Viscerosensory information is conveyed to the nucleus of the solitary tract (NTS) where it initiates neuroendocrine, behavioral, and autonomic reflex responses that ensure optimal internal organ function. This excitatory input is modulated by diverse, local inhibitory interneurons, whose functions are not clearly understood. Here we show that, in male rats, 65% of somatostatin-expressing (SST) NTS neurons also express GAD67, supporting their likely role as inhibitory interneurons. Using wholecell recordings of NTS neurons, from horizontal brainstem slices of male and female SST-yellow fluorescent protein (YFP) and SSTchannelrhodopsin 2 (ChR2)-YFP mice, we quantified the impact of SST-NTS neurons on viscerosensory processing. Light-evoked excitatory photocurrents were reliably obtained from SST-ChR2-YFP neurons (n ϭ 16) and the stimulation-response characteristics determined. Most SST neurons (57%) received direct input from solitary tract (ST) afferents, indicating that they form part of a feedforward circuit. All recorded SST-negative NTS neurons (n ϭ 72) received SST-ChR2 input. ChR2-evoked PSCs were largely inhibitory and, in contrast to previous reports, were mediated by both GABA and glycine. When timed to coincide, the ChR2-activated SST input suppressed ST-evoked action potentials at second-order NTS neurons, demonstrating strong modulation of primary viscerosensory input. These data indicate that the SST inhibitory network innervates broadly within the NTS, with the potential to gate viscerosensory input to powerfully alter autonomic reflex function and other behaviors.

The effect of exogenous secretin on pancreatic carcinogenesis in WO strain hamsters has been examined in the nitrosamine-ductular adenocarcinoma model. Secretin, 20 clinical U/kg, stimulated a maximal secretory response of pancreatic juice and bicarbonate when given iv. The same dose given sc for 6 weeks had no significant effect on pancreatic wet weight and DNA or RNA contents. However, when given to animals receiving N-nitrosobis(2-oxopropyl)amine [(BOP) CAS: 60599-38-4] (5 mg/kg), it reduced the latency and increased the induction rate of tumor development when compared with the carcinogen given alone to animals (secretin + BOP, 15 of 17 animals with tumors; BOP alone, 4 of 13 with tumors at 15 wk; P less than .002). These effects are consistent with secretin acting as a cocarcinogen in this model of pancreatic carcinogenesis.

Despite recent advances in the delivery of nutritional support, cachexia continues to contribute to the morbidity and mortality of cancer patients. This impasse has called for a review of the many factors that are believed to be associated with weight loss in the cancer host. This article reviews the topic with a view to past problems and areas for investigation in the future.