title: Signaling the brain in the early sickness syndrome: are sensory nerves involved?
abstract: Nonspecific manifestations (sickness symptoms) of inflammation and infection occur as two sequential syndromes, the early and late. This review deals with the early sickness syndrome, which occurs at the onset of the inflammatory process and manifests itself with a high deep body temperature, hyperalgesia/allodynia, arousal, motor agitation, and arterial hypertension. Two rat models of intravenous lipopolysaccharide (LPS)-induced fever are used to study the early syndrome: 1) a monophasic response to low, just suprathreshold doses of LPS and 2) the first rise in body temperature (Phase I) of the polyphasic response to higher doses. Experiments in the first model reveal a blockade of monophasic fever by total subdiaphragmatic or selective hepatic vagotomy, thus suggesting mediation of this response by the hepatic vagal fibers, presumably afferent. Experiments in the second model show that Phase I of polyphasic fever is insensitive to surgical vagotomy but does not occur in animals desensitized with low intraperitoneal doses of capsaicin (an agonist of the vanilloid receptor VR1). These findings suggest that Phase I is mediated by intra-abdominal, VR1-receptor-bearing afferents, either splanchnic or possibly splanchnic and vagal. The involvement of the splanchnic nerve and VR1 receptor in Phase I of LPS fever is currently under investigation in our laboratory. Based on studies completed so far, neural signaling mechanisms are involved in both monophasic fever and Phase I of polyphasic fever. We speculate that these mechanisms are triggered by peripherally originated, blood-borne prostaglandin E2.
authors.affiliation: Systemic Inflammation Laboratory, Trauma Research, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA. aromano@chw.edu
authors.forename: Andrej A
authors.initials: AA
authors.lastname: Romanovsky
mesh_terms: D000818:Animals; D005334:Fever / Q000503:physiopathology*; D006801:Humans; D009475:Neurons, Afferent; D013577:Syndrome; D014628:Vagotomy / Q000009:adverse effects