Involvement of capsaicin-sensitive nerves in regulating the hormone and glucose metabolic response to endotoxin

This study investigated the role that sensory nerves play in mediating the hormone and glucose metabolic response to endotoxin [lipopolysaccharide (LPS)]. Adult rats were pretreated subcutaneously with capsaicin to selectively destroy primary sensory afferent nerve fibers. Ten days later, [3-³H]glucose was infused intravenously to assess whole body glucose flux before and after the intravenous injection of Escherichia coli LPS (100 μg/100 g body wt). Control animals responded to LPS with characteristic increases in the plasma concentration of glucose (91%) and lecture (threefold) and elevations in the rates of glucose appearance and disappearance (77%). In capsaicin-treated rats, the maximal LPS-induced increase in these parameters was attenuated by 50-60%. In addition, these animals were hypoglycemic at the conclusion of the experiment. Control animals demonstrated early and sustained elevations in circulating levels of corticosterone, glucagon, and catecholamines. In contrast, the early LPS- induced elevation in epinephrine and norepinephrine, and to a lesser extent glucagon, was completely absent or greatly impaired by capsaicin pretreatment. In a separate study, the epinephrine-induced increase in glucose flux was blunted by 75% in capsaicin-treated rats. These data indicate that sensory afferent neurons play a critical role in the early secretory response of glucagon and catecholamines, the maintenance of tissue catecholamine responsiveness, and the stimulation of glucose production after LPS.