title: Absence of diabetic hyperalgesia in bradykinin B1 receptor-knockout mice.
abstract: Experimental evidence has shown that the inducible bradykinin (BK) B1 receptor (BKB1-R) subtype is involved in the development of hyperalgesia associated with type 1 diabetes. Selective BKB1-R antagonists inhibited, whereas selective agonists increased the hyperalgesic activity in diabetic mice in thermal nociceptive tests. Here we evaluate the development of diabetic hyperalgesia in a BKB1-R-knockout (KO) genotype compared to wild-type (WT) mice. The BKB1-R-KO mice were backcrossed for 10 generations to C57BL/6 genetic background before use in the experiments. Diabetes was induced by streptozotocin (STZ) and thermal nociception was assessed by the hot plate and tail immersion tests. The hyperalgesia observed in wild type mice was totally absent in the BKB1-R-KO mice. Furthermore, the selective BKB1-R agonist, desArg9BK, significantly increased the hyperalgesic activity in diabetic WT mice but had no effect on nociceptive responses in diabetic BKB1-R-KO mice. Taken together, the results confirm the crucial role of the BKB1-R, upregulated alongside inflammatory diabetes, in the development of diabetes-induced hyperalgesia.
authors.affiliation: Institute of Pharmacology of Sherbrooke, School of Medicine, University of Sherbrooke, Sherbrooke, PQ, Canada J1H 5N4.
authors.forename: Bichoy H
authors.initials: BH
authors.lastname: Gabra
authors.forename: Vanessa F
authors.initials: VF
authors.lastname: Merino
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: João B
authors.initials: JB
authors.lastname: Pesquero
authors.forename: Pierre
authors.initials: P
authors.lastname: Sirois
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D003929:Diabetic Neuropathies / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006930:Hyperalgesia / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010147:Pain Measurement; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D043783:Receptor, Bradykinin B1; C024626:bradykinin, des-Arg(9)-; D001920:Bradykinin