BACKGROUND: Spinal anticholinesterase has been shown to have an antinociceptive action to acute noxious stimuli. The purpose of this study was to determine the effect of intrathecal anticholinesterase on the facilitated state developed after tissue injury evoked by formalin injection. METHODS: Rats were implanted with lumbar intrathecal catheters. For nociceptive test, 50 microliter of 5% formalin solution was injected into the hindpaw. The effect of pretreatment with intrathecal neostigmine, physostigmine and edrophonium, administered 10 min before formalin injection, was observed for 60 min. For the evaluation of the effect of posttreatment with intrathecal anticholinesterase, administered 9 min after formalin injection, the response was observed for 50 min. RESULTS: Formalin injection into the paw resulted in a biphasic incidence of flinching of the injected paw. Intrathecal pretreatment with neostigmine, physostigmine and edrophonium produced a dose- dependent suppression of the flinching during phase 1 and phase 2 on the formalin test. Posttreatment with three intrathecal anticholinesterases reduced the phase 2 flinching response. CONCLUSIONS: Both pretreatment and posttreatment with intrathecal anticholinesterase produced an antinociception on the formalin test. These results point out the usefulness of anticholinesterase to acute nociception and facilitated state.