Absence of diabetic hyperalgesia in bradykinin B 1 receptor-knockout mice

Abstract

Experimental evidence has shown that the inducible bradykinin (BK) B 1 receptor (BKB 1-R) subtype is involved in the development of hyperalgesia associated with type 1 diabetes. Selective BKB 1-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 BKB 1-R-knockout (KO) genotype compared to wild-type (WT) mice. The BKB 1-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 BKB 1-R-KO mice. Furthermore, the selective BKB 1-R agonist, desArg 9BK, significantly increased the hyperalgesic activity in diabetic WT mice but had no effect on nociceptive responses in diabetic BKB 1-R-KO mice. Taken together, the results confirm the crucial role of the BKB 1-R, upregulated alongside inflammatory diabetes, in the development of diabetes-induced hyperalgesia.