PENTOBARBITAL, BUT NOT PROPOFOL, PRODUCES PREEMPTIVE ANALGESIA IN THERAT FORMALIN MODEL

Injection of formalin into the hindpaw of a rat induces a biphasic res ponse in pain-related behaviours, such that C-fibre activation during phase I triggers a state of central sensitization characterized by a l onger lasting phase 2. As the inhibitory neurotransmitter gamma-aminob utyric acid (GABA) may participate in processing of nociceptive inputs , we hypothesized that pentobarbitone and propofol, iv. anaesthetics w ith known GABA(A) agonist properties, would interfere with development of central sensitization and thereby modify the phase 2 hyperalgesic response. Pentobarbitone administered i. v. before injection of formal in produced dose-dependent suppression of phase 2, even though animals had recovered from anaesthesia, whereas it had substantially less eff ect when given after phase 1 had resolved. Picrotoxin, a GABA(A) antag onist, 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 pent obarbitone, but not propofol, produced pre-emptive analgesia in this m odel, presumably by suppressing noxious stimulation-induced central se nsitization via activation of GABA(A) receptors.