NEUROCIRCUITRY OF ILLNESS-INDUCED HYPERALGESIA

We have previously demonstrated that illness-inducing agents such as l ithium chloride (LiCl) and the bacterial cell wall endotoxin lipopolys accharide (LPS) produce hyperalgesia on diverse pain measures. The pre sent series of studies attempted to identify the neurocircuitry mediat ing these effects. These studies have demonstrated that illness-induci ng agents produce hyperalgesia by activating: (a) peripheral nerves ra ther than by generating a blood-borne mediator (Expt. 1); (b) vagal af ferents, specifically afferents within the hepatic branch of the vagus (Expt. 2); (c) as yet unidentified brain site(s) rostral to the mid-m esencephalon (Expt. 6); (d) a centrifugal pathway that arises from the nucleus raphe magnus, and not from the adjacent nucleus reticularis p aragigantocellularis pars alpha (Expts. 4 and 5); (e) a centrifugal pa thway 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.