The kinin system mediates hyperalgesia through the inducible bradykinin B1 receptor subtype: evidence in various experimental animal models of type 1 and type 2 diabetic neuropathy.
Both insulin-dependent (type 1) and insulin-independent (type 2) diabetes are complex disorders characterized by symptomatic glucose intolerance due to either defective insulin secretion, insulin action or both. Unchecked hyperglycemia leads to a series of complications among which is painful diabetic neuropathy, for which the kinin system has been implicated. Here, we review and compare the profile of several experimental models of type 1 and 2 diabetes (chemically induced versus gene-prone) and the incidence of diabetic neuropathy upon aging. We discuss the efficacy of selective antagonists of the inducible bradykinin B1 receptor (BKB1-R) subtype against hyperalgesia assessed by various nociceptive tests. In either gene-prone models of type 1 and 2 diabetes, the incidence of hyperalgesia mostly precedes the development of hyperglycemia. The administration of insulin, achieving euglycemia, does not reverse hyperalgesia. Treatment with a selective BKB1-R antagonist does not affect basal nociception in most normal control rats, whereas it induces a significant time- and dose-dependent attenuation of hyperalgesia, or even restores nociceptive responses, in experimental diabetic neuropathy models. Diabetic hyperalgesia is absent in streptozotocin-induced type 1 diabetic BKB1-R knockout mice. Thus, selective antagonism of the inducible BKB1-R subtype may constitute a novel and potential therapeutic approach for the treatment of painful diabetic neuropathy.
IPS Pharma Inc., Sherbrooke J1H 5N4, QC, Canada.
Bichoy H
BH
Gabra
Nathalie
N
Berthiaume
Pierre
P
Sirois
François
F
Nantel
Bruno
B
Battistini
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D065169:Bradykinin B1 Receptor Antagonists; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000188:drug therapy; D004195:Disease Models, Animal; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism*; D016234:Kallikrein-Kinin System / Q000502:physiology*; D043783:Receptor, Bradykinin B1 / Q000172:deficiency / Q000378:metabolism*
D000927:Anticonvulsants; D065169:Bradykinin B1 Receptor Antagonists; D043783:Receptor, Bradykinin B1