Inhibition of type 1 diabetic hyperalgesia in streptozotocin-induced Wistar versus spontaneous gene-prone BB/Worchester rats: efficacy of a selective bradykinin B1 receptor antagonist.
Insulin-dependent type 1 diabetes (T1D) is linked to a series of complications, including painful diabetic neuropathy (PDN). Several neurovascular systems are activated in T1D, including the inducible bradykinin (BK) B1 receptor (BKB1-R) subtype. We assessed and compared the efficacy profile of a selective BKB1-R antagonist on hyperalgesia in 2 models of T1D: streptozotocin (STZ) chemically induced diabetic Wistar rats and spontaneous BioBreeding/Worchester diabetic-prone (BB/Wor-DP) rats. Nociception was measured using the hot plate test to determine thermal hyperalgesia. STZ diabetic rats developed maximal hyperalgesia (35% decrease in their hot plate reaction time) within a week and remained in such condition and degree for up to 4 weeks postinjection. BB/Wor-DP rats also developed hyperalgesia over time that preceded hyperglycemia, starting at the age of 6 weeks (9% decrease in the hot plate reaction time) and stabilizing over the age of 16 to 24 weeks to a maximum (60% decrease in the hot plate reaction time). Single, acute subcutaneous administration of the selective BKB1-R antagonist induced significant time- and dose-dependent attenuation of hyperalgesia in both STZ diabetic and BB/Wor-DP rats. Thus, selective antagonism of the inducible BKB1-R subtype may constitute a novel and potential therapeutic approach for the treatment of PDN.
Gabra
Bichoy H
BH
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Canada.
Benrezzak
Ouhida
O
Pheng
Leng-Hong
LH
Duta
Dana
D
Daull
Philippe
P
Sirois
Pierre
P
Nantel
François
F
Battistini
Bruno
B
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D065169:Bradykinin B1 Receptor Antagonists; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000235:genetics; D003929:Diabetic Neuropathies / Q000188:drug therapy; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar
C476306:Ac-Orn-(Oic2, alpha-MePhe5, D-betaNal7, Ile8)desArg9-bradykinin; D065169:Bradykinin B1 Receptor Antagonists; D001920:Bradykinin