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

• Published in: Neuropharmacology Vol. 53; no. 1; pp. 48 - 57
• Main Authors: Werner, M.F.P., Kassuya, C.A.L., Ferreira, J., Zampronio, A.R., Calixto, J.B., Rae, G.A.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-07-2007
• Subjects: Cold allodynia; Heat hyperalgesia; Kinin B 1 and B 2 receptors; Neuropathic pain; Spinal nerve ligation; Tactile allodynia; Spinal nerve ligation; Kinin B 1 and B 2 receptors; Heat hyperalgesia; Tactile allodynia; Cold allodynia; Neuropathic pain
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2007.04.013

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 0.01–1
nmol/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; 0.1–1
μmol/kg, i.p.) selectively blocked responses triggered by DABK and BK (1
nmol/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.