The involvement of tachykinin NK2 and NK3 receptors in central sensitization of a spinal withdrawal reflex in the decerebrated, spinalized rabbit

Repetitive electrical stimulation of the sural nerve at a strength sufficie nt to excite C-fibres results in prolonged (> 20 min) increases in the refl ex responses of gastrocnemius motoneurones evoked by stimulation of myelina ted axons in the sural nerve. We have tested the susceptibility of this eff ect to blockade of tachykinin NK2 and NK3 receptors. Ln the control state, iterative stimulation of sural nerve C fibres increased gastrocnemius refle xes to a peak of between 200 and 400% of pre-stimulus levels, an effect tha t recovered to baseline values over 23-30 min. Pre-treatment with selective antagonists for NK2 (SR 48968, 1 mg/kg i.v.) or NK3 (SR 142801, 0.1 and 1 mg/kg i.v.) receptors failed to alter the peak facilitation resulting from sural nerve stimulation. However, both drugs significantly reduced the dura tion of enhancement of reflexes, to 18 min after SR 48968 and to 5 min afte r SR 142801. The inactive enantiomers of these compounds (SR 48965 and SR 1 42806, both 1 mg/kg i.v.) did not reduce facilitation of reflexes after sur al nerve stimulation. We conclude that activation of tachykinin NK3 recepto rs is a major factor in maintaining central sensitization of the sural-gast rocnemius reflex after electrical stimulation of sural nerve C-fibres. The effects of SR 48968 were surprisingly weak and may have resulted from an ef fect of this compound at NK, receptors. (C) 1999 Elsevier Science Ltd. All rights reserved.