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.


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.
Gabra
B H
BH
Institute of Pharmacology of Sherbrooke, School of Medicine, University of Sherbrooke, Sherbrooke, J1H 5N4, PQ, Canada.
Sirois
P
P
D000818:Animals; D065169:Bradykinin B1 Receptor Antagonists; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006930:Hyperalgesia / Q000150:complications* / Q000378:metabolism*; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D015398:Signal Transduction; D013311:Streptozocin / Q000494:pharmacology; D013373:Substance P / Q000037:antagonists & inhibitors / Q000378:metabolism
D065169:Bradykinin B1 Receptor Antagonists; D004791:Enzyme Inhibitors; D043783:Receptor, Bradykinin B1; D013373:Substance P; D013311:Streptozocin; D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide