Bradykinin receptor antagonists and cyclooxygenase inhibitors in vincristine- and streptozotocin-induced hyperalgesia.
Pain that accompanies neuropathy is difficult to treat. Analgesics administered as monotherapies possess low activities in relieving this kind of pain. The effect of the simultaneous administration of indomethacin (a preferential inhibitor of cyclooxygenase-1; COX-1) or celecoxib (a relatively selective inhibitor of cyclooxygenase-2; COX-2), with selective antagonists of bradykinin(2) (B(2)) bradykinin(1) (B(1)) receptors (HOE 140 or des-Arg(10)-HOE 140) on the alleviation of diabetic and toxic neuropathic pain was investigated. Pretreatment with indomethacin (0.1 mg/kg, sc) increased the antihyperalgesic activity of low daily doses of HOE 140 or des-Arg(10)HOE 140 (70 nmol/kg, ip) in a diabetic (streptozotocin(STZ)-induced) neuropathy/hyperalgesia experimental model. Premedication with celecoxib before HOE 140 or des-Arg(10)HOE 140 administration resulted in a gradual reduction of STZ hyperalgesia. Furthermore, on days 23-24, almost complete abolishment of STZ hyperalgesia was observed. After cessation of drug administration, hyperalgesia quickly returned to the baseline threshold. The results of this study suggest that inhibitors of cyclooxygenases can increase the antihyperalgesic activity of selective antagonists of B(2) and B(1) receptors in diabetic and toxic neuropathic pain models. These observations may be clinically relevant.
Bujalska
Magdalena
M
Department of Pharmacodynamics, Medical University of Warsaw, Krakowskie Przedmieście 26/28, PL 00-927 Warszawa, Poland. mbujalska@gmail.com
Makulska-Nowak
Helena
H
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004357:Drug Synergism; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000502:physiology; D013311:Streptozocin / Q000633:toxicity*; D014750:Vincristine / Q000633:toxicity*
D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D018002:Receptors, Bradykinin; D014750:Vincristine; D013311:Streptozocin; C065679:icatibant; D001920:Bradykinin