Pentobarbitone, but not propofol, produces pre-emptive analgesia in the rat formalin model

Injection of formalin into the hindpaw of a rat induces a biphasic response in pain-related behaviours, such that C-fibre activation during phase 1 triggers a state of central sensitization characterized by a longer lasting phase 2. As the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) may participate in processing of nociceptive inputs, we hypothesized that pentobarbitone and propofol, i.v. anaesthetics with known GABAA agonist properties, would interfere with development of central sensitization and thereby modify the phase 2 hyperalgesic response. Pentobarbitone administered i.v. before injection of formalin produced dose-dependent suppression of phase 2, even though animals had recovered from anaesthesia, whereas it had substantially less effect when given after phase 1 had resolved. Picrotoxin, a GABAA antagonist, reversed the effect of pentobarbitone on phase 2 pain behaviour but was itself a mild analgesic. In contrast, propofol had no effect on phase 2 formalin-induced pain behaviour. Thus we conclude that pentobarbitone, but not propofol, produced pre-emptive analgesia in this model, presumably by suppressing noxious stimulation-induced central sensitization via activation of GABAA receptors.