Pathways for the bradykinin B1 receptor-mediated diabetic hyperalgesia in mice.

OBJECTIVE

Experimental evidence has shown that the bradykinin B1 receptor (BKB1-R) is involved in the development of hyperalgesia associated with diabetes since specific BKB1-R antagonists significantly inhibited the hyperalgesic activity observed in streptozotocin (STZ)-mice in thermal nociceptive tests.

MATERIALS AND METHODS

The involvement of the nitric oxide (NO), the substance P (SP) and the calcitonin gene-related peptide (CGRP) pathways in mediating BKB1-R-induced hyperalgesia was evaluated. Diabetes was induced in male CD-1 mice by injecting STZ (200 mg/kg; i.p.). Nociception was assessed using the hot plate and tail immersion tests, one week following the injection of STZ.

RESULTS

The nitric oxide synthase (NOS) inhibitors (L-NNA, 20 mg/kg; L-NMMA, 30 mg/kg and AGUA, 50 mg/kg; i.p.), the SP antagonists (sendide and L-732,138, 100 microg/kg; i.v.) and the CGRP antagonist (hCGRP8-37, 100 microg/kg; i.v.) significantly attenuated the hyperalgesic activity and also reversed the potentiating effect of the BKB1- R agonist, DBK on diabetic hyperalgesia in STZ-mice.

CONCLUSIONS

These results support the involvement of BKB1-R in the development of diabetic hyperalgesia in STZ-mice through activation of the NO, SP and CGRP pathways.