Gabapentin and pregabalin, but not morphine and amitriptyline, block both static and dynamic components of mechanical allodynia induced by streptozocin in the rat

A single injection of streptozocin (50 mg/kg, i.p.) led to the development of static and dynamic allodynia in the rat. The two responses were detected , respectively, by application of pressure using von Frey hairs or lightly stroking the hind paw with a cotton bud. Static allodynia was present in th e majority of the animals within 10 days following streptozocin. In contras t, dynamic allodynia took almost twice as long to develop and was only pres ent in approximately 60% of rats. Morphine (1-3 mg/kg, s.c.) and amitriptyl ine (0.25-2.0 mg/kg, p.o.) dose-dependently blocked static allodynia. Howev er, neither of the compounds was effective against dynamic allodynia. In co ntrast, gabapentin (10-100 mg/kg, p.o.) and the related compound pregabalin (3-30 mg/kg, p.o.) dose-dependently blocked both types of allodynia. Howev er, the corresponding R-enantiomer (10-100 mg/kg, p.o.) of pregabalin, was found to be inactive. The intrathecal administration of gabapentin dose-dep endently (1-100 mu g/animal) blocked both static and dynamic allodynia. In contrast, administration of similar doses of gabapentin into the hind paw f ailed to block these responses. It is suggested that in this model of neuro pathic pain dynamic allodynia is mediated by A beta-fibres and the static t ype involves small diameter nociceptive fibres. These data suggest that gab apentin and pregabalin possess a superior antiallodynic profile than morphi ne and amitriptyline, and may represent a novel class of therapeutic agents for the treatment of neuropathic pain. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V.