Purpose To test the hypotheses that greater initial body weight is associated with a relative improvement in survival with diminished fibrosis in a diethylnitrosamine (DEN)-induced rat model of HCC and that TAE (TAE) via femoral artery access decreases procedure times compared to carotid artery access. Materials and Methods 138 male Wistar rats were administered 0.01% DEN in water ad libitum for 12 weeks. Rats received weekly T2-MRI to detect HCC. Upon development of ≥5mm tumors, rats underwent selective TAE via carotid or femoral artery catheterization under fluoroscopic guidance. Rats were retrospectively categorized into 3 groups (<300g, 300-400g, >400g) based on initial weight for analyses of survival, tumor latency, and fibrosis. Site of access was compared relative to procedural outcomes of success, mortality, and time. Results No significant differences in tumor latency were related to weight group (p=0.310). Rats weighing <300g had shorter survival time than both larger groups (mean=88d vs. 108d, p<0.0001) and more severe fibrosis (<300g median=4.0, 300-400g median=1.5, >400g median=1.0; p=0.015). No significant difference was found in peri-procedural mortality based on access site; however, procedure times were shorter via a femoral approach (mean=71+/-23min vs. 127+/-24min; p<0.0001). Conclusion Greater initial body weight resulted in improved survival without prolonging tumor latency for rats with DEN-induced HCCs and was associated with less severe fibrosis. A femoral approach for TAE in this model resulted in decreased procedure time. These modifications provide a translational animal model of HCC and TAE that may be suited for short-term survival studies.

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Hunger is a primal biological drive that can initiate behavioral changes. Intuitively, hunger can inhibit behaviors such as sleep while simultaneously promoting foraging. Because pain can prevent an animal from seeking food we questioned if hunger could suppress pain. We found that food deprived mice reduce their response to inflammatory nociceptive stimuli. This reduction in nocifensive behavior during hunger is specific to inflammatory pain as the response to acute thermal and mechanical nociceptive stimuli remains intact. During hunger, agouti-related protein expressing (AgRP) neurons in the hypothalamus become active. AgRP neuron activation is both necessary and sufficient for feeding behavior and is thus a way to model hunger without the peripheral complications. Importantly, activating AgRP neurons recapitulates the analgesic effects of hunger. Because food deprivation reduces inflammatory pain responses, we next explored the influence of hunger and AgRP neuron activity on peripheral inflammation. To address this question, we measured paws after an injection of Complete Freund’s Adjuvant (CFA) in food deprived mice. We found that food deprivation was able to reduce CFA-induced paw inflammation compared to ad libitum fed controls. To assess the role of the AgRP circuit on inflammation, we measured CFA injected paws during optogenetic stimulation of AgRP neurons. Optogenetic activation of AgRP neurons rapidly reduces paw inflammation. This rapid and robust reduction in peripheral inflammation following activity in a CNS circuit suggests that AgRP neuron activity interacts with the immune system. Current experiments are aimed to determine the CNS à immune pathway that quickly reduces peripheral inflammation.

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