Antinociceptive activities of lidocaine and the nav1.8 blocker a803467 in diabetic rats

PubMedID: 23312086The streptozocin-induced diabetic rat is a model of chronic pain that shows signs of hyperalgesia and allodynia and may replicate signs in diabetic humans. Here we investigated the antinociceptive effects of A803467, a highly selective blocker of Nav1.8 channels, in diabetic rats with painful neuropathy. We systemically (intraperitoneal) or locally (intraplantar) administered A803467 (or lidocaine, a nonselective sodium channel blocker, as a control) to diabetic rats with hyperalgesia and allodynia and then measured thermal latencies and mechanical thresholds. With intraperitoneal administration, A803467 led to 6-fold greater reduction of hyperalgesia and 2-fold greater reduction of allodynia than did lidocaine. Whereas the antihyperalgesic effects of lidocaine and A803467 were similar after intraplantar administration, A803467 (1 mg) was at least 2 times more effective as an antiallodynic than was lidocaine (0.5 mg). These results suggest that compared with lidocaine, systemic or local blockade of Nav1.8 channels by A803467 may more effectively relieve hyperalgesia and allodynia in diabetic neuropathy. Copyright © 2012 by the American Association for Laboratory Animal Science