Acute phenobarbital administration induces hyperalgesia: pharmacological evidence for the involvement of supraspinal GABA-A receptors

The aim of the present study was to determine if phenobarbital affects the nociception threshold. Systemic (1-20 mg/kg) phenobarbital administration d ose dependently induced hyperalgesia in the tail-flick, hot-plate and forma lin tests in rats and in the abdominal constriction test in mice. Formalin and abdominal constriction tests were the most sensitive procedures for the detection of hyperalgesia in response to phenobarbital compared with the t ail-flick and hot-plate tests. The hyperalgesia induced by systemic phenoba rbital was blocked by previous administration of 1 mg/kg ip picrotoxin or e ither 1-2 mg/kg sc or 10 ng icv bicuculline. Intracerebroventricular phenob arbital administration (5 mug) induced hyperalgesia in the tail-flick test. In contrast, intrathecal phenobarbital administration (5 mug) induced anti nociception and blocked systemic-induced hyperalgesia in this test. We sugg est that phenobarbital may mediate hyperalgesia through GABA-A receptors at supraspinal levels and antinociception through the same kind of receptors at spinal levels.