title: Capsaicin-sensitive nerves regulate the metabolic response to abdominal sepsis.
abstract: BACKGROUND
  Both the systemic release of inflammatory mediators and activation of the neuroendocrine axis by sensory afferent nerves (SANs) have been implicated as initiators of the metabolic response to infection. In this study, we investigate the role of SANs as mediators of protein catabolism and the insulin-like growth factor (IGF) axis during abdominal sepsis using capsaicin (Cap) to selectively destroy nociceptive sensory axons.
  
  
  METHODS
  Four groups of male Sprague-Dawley rats were studied: Control, Control+Cap, Sepsis, and Sepsis+Cap. Rats were injected with Cap (75 mg/kg) on day 1 and (50 mg/kg) on day 2 to destroy SANs. Time-matched control and septic rats were pair-fed and injected with vehicle on the same schedule. Controls underwent sham laparotomy, while septic rats had a fecal-agar pellet inoculated with Escherichia coli and Bacteroides fragilis implanted in the peritoneal cavity. Blood and tissues were harvested 5 days after the induction of sepsis. Plasma IGF-I, IGFBP-1, and -3 were measured by radioimmunoassay and Western blot analysis. IGF-I, acid-labile subunit (ALS), IGFBP-1 and -3 mRNA levels were determined by Northern blot analysis.
  
  
  RESULTS
  Mortality was 40% in septic rats vs 0% in the sepsis+Cap group. Capsaicin had no effect on muscle mass, protein content, or the IGF system in control rats. However, sepsis-induced reductions in gastrocnemius mass (25%) and protein content (35%) were ameliorated by capsaicin. The sepsis-induced decrease in hepatic IGF-I mRNA and circulating IGF-I (26%), as well as the 4-fold increase in plasma IGFBP-1 and hepatic IGFBP-1 mRNA were prevented by capsaicin.
  
  
  CONCLUSIONS
  Capsaicin-sensitive nerves mediate mortality, the catabolism of skeletal muscle, and selected elements of the IGF system during abdominal sepsis. The results suggest an important role for nociceptive SANs and the neuroendocrine system in mediating the host response to abdominal infection.
authors.affiliation: Department of Surgery, The Penn State College of Medicine, Hershey, Pennsylvania 17033, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bryant
authors.forename: Margaret
authors.initials: M
authors.lastname: Shumate
authors.forename: Gladys
authors.initials: G
authors.lastname: Yumet
authors.forename: Charles H
authors.initials: CH
authors.lastname: Lang
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Vary
authors.forename: Robert N
authors.initials: RN
authors.lastname: Cooney
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D004435:Eating; D007328:Insulin / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism*; D010538:Peritonitis / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D020738:Leptin; D011506:Proteins; D007334:Insulin-Like Growth Factor I; D002211:Capsaicin