Peripheral kinin B(1) and B(2) receptor-operated mechanisms are implicated in neuropathic nociception induced by spinal nerve ligation in rats.

The kinin system can contribute distinctly to the sensory changes associated with different models of nerve injury-induced neuropathic pain. This study examines the roles of kinin B(1) and B(2) receptor-operated mechanisms in alterations in nociceptive responses of rats submitted to unilateral L5/L6 spinal nerve ligation (SNL) injury. Behavioural responses to ipsilateral hind paw stimulation with acetone (evaporation-evoked cooling), radiant heat (Hargreaves method) or von Frey hairs revealed that SNL rats developed long-lasting cold allodynia (from Days 3 to 40 post-surgery, peak on Day 6), heat hyperalgesia (stable peak from Days 9 to 36) and tactile allodynia (stable peak from Days 3 to 51). SNL rats manifested nocifensive responses to intraplantar injections on Day 12 of the selective B(1) receptor agonist des-Arg(9)-bradykinin (DABK) and augmented responses to the selective B(2) receptor agonist bradykinin (BK; each at 0.01-1nmol/paw). Systemic treatment of SNL rats with des-Arg(9)-Leu(8)-BK or HOE 140 (peptidic B(1) and B(2) receptor antagonists, respectively; 0.1-1mumol/kg, i.p.) selectively blocked responses triggered by DABK and BK (1nmol/paw) and alleviated partially and transiently established cold allodynia, heat hyperalgesia and (to a lesser extent) tactile allodynia. Western blot analysis revealed enhanced expression of kinin B(1) and B(2) receptor protein in ipsilateral L4-L6 spinal nerve and hind paw skin samples collected on Day 12 after SNL surgery. These results indicate that peripheral pronociceptive kinin B(1) and B(2) receptor-operated mechanisms contribute significantly to the maintenance of hind paw cold and mechanical allodynia and heat hyperalgesia induced by L5/L6 SNL in rats.

Importance of the vagus nerve for fever and neutrophil migration induced by intraperitoneal LPS injection.

OBJECTIVE: We investigated the importance of the vagus nerve in fever, neutrophil migration and neutrophilia simultaneously induced by intraperitoneal injection of endotoxin (lipopolysaccharide, LPS) and in terms of the production of pre-formed pyrogenic factor (PFPF) and of the fever induced by this factor. METHODS: Naïve, sham-operated or subdiaphragmatically vagotomized male Wistar rats received either LPS (i.p. or i.pl.) or PFPF (i.v., i.c.v., i.p.). The number of neutrophils was evaluated in peritoneal or pleural fluid and in blood. Fever was monitored using a rectal probe. RESULTS: In naïve animals, LPS (0.02-200 microg kg(-1), i.p.) induced dose-related neutrophilia and fever while on neutrophil migration it resulted in a bell-shaped curve. Vagotomy reduced the peritoneal resident cell population (56%), fever (71%) and neutrophil migration (43%) but not the neutrophilia or neutrophil migration to the pleural cavity. Vagotomy did not affect the PFPF production or PFPF-induced fever. CONCLUSIONS: Vagus nerve integrity is important not only for fever but also for the neutrophil influx to the peritoneal cavity by controlling the number of resident cells in this cavity.