Antinociceptive effects of peripheral benzodiazepine receptors.
Pretreatment of mice with Ro5-4864 or PK11195 inhibited the first- and second-phase responses in the formalin test and this effect was significantly reversed by aminoglutethimide, an inhibitor of pregnenolone synthesis, suggesting that the antinociceptive effect of the peripheral-type benzodiazepine receptor ligands is dependent on steroid formation. Doses of Ro5-4864 that did not produce an antinociceptive effect when injected by the intraperitoneal route presented an analgesic effect, if infected by the intracerebroventricular, intrathecal or intraplantar routes. PK11195 pretreatments with intrathecal, intracerebroventricular or intraplantar doses had no effect in the formalin test. These results suggest that the antinociceptive effect of Ro5-4864 reflects the influence of this ligand on steroid production not only in many nonneuronal peripheral tissues but also in the nervous system, while the antinociceptive action of PK11195 may be due to the stimulation of steroid synthesis only in nonnervous tissues.
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Silvia
S
DalBó
Geisson M
GM
Nardi
Pascual
P
Ferrara
Rosa M
RM
Ribeiro-do-Valle
Roseli C
RC
Farges
D000616:Aminoglutethimide / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005528:Foot; D005557:Formaldehyde; D007267:Injections; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects*; D017933:Peripheral Nervous System / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D013256:Steroids / Q000502:physiology
D000700:Analgesics; D001570:Benzodiazepinones; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D011963:Receptors, GABA-A; D013256:Steroids; D000616:Aminoglutethimide; D005557:Formaldehyde; C028513:4'-chlorodiazepam; C037850:PK 11195