HYPERALGESIA IN RATS FOLLOWING INTRACEREBROVENTRICULAR ADMINISTRATIONOF ENDOTOXIN - EFFECT OF BRADYKININ B-1 AND B-2 RECEPTOR ANTAGONIST TREATMENT

The present study investigated the development of thermal and mechanic al hyperalgesia following intracerebroventricular (i.c.v.) injections of E. coli lipopolysaccharide (LPS). Hind paw withdrawal to von Frey f ilament stimulation and thermal withdrawal latencies were measured bef ore and up to 24 or 48 h following an i.c.v. injection of LPS (dose ra nge: 0.02-200 mu g). Thermal and mechanical hyperalgesia were evident by 6 h after LPS injection. LPS-induced hyperalgesia was reversed by t he B-2 receptor antagonist, HOE 140 (10-30 pmol), when administered i. c.v. but not systemically (0.01-1 mmol/kg, i.v.). Central co-administr ation of the B-1 receptor antagonists, des-Arg(9)-Leu(8) Bk (0.1-1 nmo l) or des-Arg(10) HOE 140 (0.1-1 nmol) had no effect on thermal or mec hanical hyperalgesia. LPS-induced hyperalgesia was also inhibited by i ndomethacin administered either i.c.v. (10 nmol) or i.v. (1 mu mol/kg) . These results indicate that administration of endotoxin to the CNS i nduces the development of hyperalgesia and that this response involves the activity of kinins, via the stimulation of centrally located B-2 receptors, and the formation of prostanoids.