title: Peripheral kinin B(1) and B(2) receptor-operated mechanisms are implicated in neuropathic nociception induced by spinal nerve ligation in rats.
abstract: 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.
authors.affiliation: Department of Pharmacology, Biological Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, 88048-900 SC, Brazil.
authors.forename: M F P
authors.initials: MF
authors.lastname: Werner
authors.forename: C A L
authors.initials: CA
authors.lastname: Kassuya
authors.forename: J
authors.initials: J
authors.lastname: Ferreira
authors.forename: A R
authors.initials: AR
authors.lastname: Zampronio
authors.forename: J B
authors.initials: JB
authors.lastname: Calixto
authors.forename: G A
authors.initials: GA
authors.lastname: Rae
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D007839:Functional Laterality; D006930:Hyperalgesia / Q000503:physiopathology; D008026:Ligation; D008297:Male; D009437:Neuralgia / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000819:agonists / Q000502:physiology*; D043782:Receptor, Bradykinin B2 / Q000819:agonists / Q000502:physiology*; D013127:Spinal Nerves / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D013997:Time Factors
chemical_list: D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; C024626:bradykinin, des-Arg(9)-; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D001920:Bradykinin