Anti-nociceptive and anxiolytic effects of systemic flupirtine and its direct inhibitory actions on in vivo neuronal mechanical sensory responses in the adult rat anterior cingulate cortex.
Flupirtine is a non-opioid centrally acting analgesic that has been in clinical use, and is reported to act on neuronal ion channels and neurotransmitter receptors. However, its action on emotional aspects of pain is still unknown. In this study, we examined whether flupirtine has anxiolytic action and assayed its direct actions on the anterior cingulate cortex (ACC) at the single neuronal and synaptic levels. Anti-nociceptive and anxiolytic effects of flupirtine were evaluated by von Frey test and elevated plus-maze (EPM) in adult rats. The effects of flupirtine on firings and synaptic currents in the rat ACC were examined using in vivo extracellular and brain slice patch-clamp recording techniques, respectively. Systemic administration of flupirtine increased paw withdrawal threshold, and reduced anxiety-like behavior in the EPM. ACC neurons fired spontaneously. Mechanical stimulation of the contralateral hind paw with the von Frey filaments increased firing from the basal spontaneous activity. Intravenous administration of flupirtine reduced both spontaneous and stimulus-evoked firing frequency in the ACC. Flupirtine microinjected into the ACC also inhibited the spontaneous and evoked-responses. In brain slices, flupirtine did not induce any detectable outward currents, but it prolonged the decay time of GABAergic inhibitory synaptic responses. These results suggest that flupirtine directly augments GABAergic synaptic currents and suppresses evoked mechanical nociceptive responses in the ACC. This direct action in the ACC may reduce emotional aspect of pain and induce anxiolytic action.
['Matsumoto|Yu|Y|', 'Fujino|Yuji|Y|', 'Furue|Hidemasa|H|']
D061605:Administration, Intravenous D000631:Aminopyridines D000700:Analgesics D000818:Animals D014151:Anti-Anxiety Agents D001522:Behavior, Animal D000082564:Elevated Plus Maze Test D006179:Gyrus Cinguli D053444:Inhibitory Postsynaptic Potentials D008297:Male D008845:Microinjections D009474:Neurons D018408:Patch-Clamp Techniques D017207:Rats, Sprague-Dawley
Central acting analgesic Emotional aspect of pain Inhibitory synaptic response Anterior cortical firing In vivo neuronal activity recording