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

Injection of formalin into the hindpaw of a rat induces a biphasicresponse in pain-related behaviours, such that C-fibre activationduring phase 1 triggers a state of central sensitization characterizedby a longer lasting phase 2. As the inhibitory neurotransmittergamma-aminobutyric acid (GABA) may participate in processingof nociceptive inputs, we hypothesized that pentobarbitone andpropofol, i.v. anaesthetics with known GABA_A agonist properties,would inten'ere with development of central sensitization andthereby modify the phase 2 hyperalgesic response. Pentobarbitoneadministered i. v. before injection of formalin produced dose-dependentsuppression of phase 2, even though animals had recovered fromanaesthesia, whereas it had substantially less effect when givenafter phase 1 had resolved. Picrotoxin, a GABA_A antagonist,reversed the effect of pentobarbitone on phase 2 pain behaviourbut was itself a mild analgesic. In contrast, propofol had noeffect on phase 2 formalin-induced pain behaviour. Thus we concludethat pentobarbitone, but not propofol, produced pre-emptiveanalgesia in this model, presumably by suppressing noxious stimulation-inducedcentral sensitization via activation of GABA_A receptors. ^*Present address: Department of Anesthesia, Teikyo University,Ichihara Hospital, 3426-3 Anesaki, Ichihara, Chiba 299-01, Japan