Neurocircuitry of illness-induced hyperalgesia

Brain Res. 1994 Mar 14;639(2):283-99. doi: 10.1016/0006-8993(94)91742-6.


We have previously demonstrated that illness-inducing agents such as lithium chloride (LiCl) and the bacterial cell wall endotoxin lipopolysaccharide (LPS) produce hyperalgesia on diverse pain measures. The present series of studies attempted to identify the neurocircuitry mediating these effects. These studies have demonstrated that illness-inducing agents produce hyperalgesia by activating: (a) peripheral nerves rather than by generating a blood-borne mediator (Expt. 1); (b) vagal afferents, specifically afferents within the hepatic branch of the vagus (Expt. 2); (c) as yet unidentified brain site(s) rostral to the mid-mesencephalon (Expt. 6); (d) a centrifugal pathway that arises from the nucleus raphe magnus, and not from the adjacent nucleus reticularis paragigantocellularis pars alpha (Expts. 4 and 5); (e) a centrifugal pathway in the dorsolateral funiculus of the spinal cord (Expt. 3); and (f) the same centrifugal pathways for diverse illness inducing agents (Expts. 3, 7 and 8). These data call for the re-evaluation of a number of assumptions inherent in previous studies of hyperalgesia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Basal Ganglia / physiology
  • Behavior, Animal / drug effects
  • Decerebrate State / physiopathology
  • Formaldehyde
  • Ganglia, Sympathetic / physiology
  • Ganglionectomy
  • Hyperalgesia / chemically induced
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology*
  • Injections, Intraperitoneal
  • Lipopolysaccharides
  • Lithium Chloride
  • Male
  • Nervous System / physiopathology*
  • Neural Pathways / physiopathology
  • Pain Measurement
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Raphe Nuclei / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reflex / physiology
  • Vagotomy


  • Lipopolysaccharides
  • Proto-Oncogene Proteins c-fos
  • Formaldehyde
  • Lithium Chloride