Chrysin induces hyperalgesia via the GABAA receptor in mice.

Chrysin (5,7-dihydroxyflavone) is a natural flavone commonly found in many plants including PASSIFLORA COERULEA L. Researchers have performed extensive and detailed investigations on the behavioral and pharmacological effects of chrysin IN VIVO, but there was little information available on the effect of chrysin on nociception. Therefore, the present study was undertaken to investigate the effect of chrysin on the nociceptive threshold using the tail-immersion test. Intraperitoneal ( I. P.) injection of chrysin (10, 25, 50, 75, 100 mg/kg) dose- and time-dependently induced a pronounced decrease of the tail withdrawal latencies (TWL), thus characterizing a hyperalgesic effect (ED50 = 65.59 mg/kg). The following results showed that GABAA receptors were involved in the hyperalgesic effects of chrysin. 1) The hyperalgesia induced by chrysin was significantly and dose-dependently blocked by pretreatment with flumazenil (0.75, 1 mg/kg, I. P.), a specific antagonist for benzodiazepine sites associated with GABAA receptors. 2) Bicuculline (2, 4 mg/kg, I. P.), a GABAA receptor antagonist, markedly antagonized the hyperalgesic effect of chrysin in a dose-dependent manner. 3) Picrotoxin (2 mg/kg, I. P.), a chloride channel blocker, could also notably antagonize the hyperalgesia of chrysin. Oral administration of chrysin (75 mg/kg) also produced a hyperalgesic effect in the tail-immersion test. In addition, diazepam (1 mg/kg, I. P.) showed a marked antinociceptive effect, which was completely blocked by flumazenil (1 mg/kg, I. P.). In conclusion, it can be summarized that both I. P. and oral administration of chrysin produced a significant hyperalgesic effect in the tail-immersion test and that the hyperalgesic effect of chrysin may be associated with GABAA receptors.