Hyperalgesia in rats following intracerebroventricular administration of endotoxin: Effect of bradykinin B-1 and B-2 receptor antagonist treatment

The present study investigated the development of thermal and mechanical hyperalgesia following intracerebroventricular (i.c.v.) injections of E. coli lipopolysaccharide (LPS). Hind paw withdrawal to von Frey filament stimulation and thermal withdrawal latencies were measured before and up to 24 or 48 h following an i.c.v. injection of LPS (dose range: 0.02-200 mu g). Thermal and mechanical hyperalgesia were evident by 6 h after LPS injection. LPS-induced hyperalgesia was reversed by the 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-administration of the B-1 receptor antagonists, des-Arg(9)-Leu(8) Bk (0.1-1 nmol) or des-Arg(10) HOE 140 (0.1-1 nmol) had no effect on thermal or mechanical hyperalgesia. LPS-induced hyperalgesia was also inhibited by indomethacin administered either i.c.v. (10 nmol) or i.v. (1 mu mol/kg). These results indicate that administration of endotoxin to the CNS induces 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.