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 sufficient to excite C-fibres results in prolonged (> 20 min) increases in the reflex responses of gastrocnemius motoneurones evoked by stimulation of myelinated axons in the sural nerve. We have tested the susceptibility of this effect to blockade of tachykinin NK2 and NK1 receptors. In the control state, iterative stimulation of sural nerve C fibres increased gastrocnemius reflexes to a peak of between 200 and 400% of pre-stimulus levels, an effect that 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 duration of enhancement of reflexes, to 18 min after SR 48968 and to 5 min after SR 142801. The inactive enantiomers of these compounds (SR 48965 and SR 142806, both 1 mg/kg i.v.) did not reduce facilitation of reflexes after sural nerve stimulation. We conclude that activation of tachykinin NK3 receptors is a major factor in maintaining central sensitization of the sural-gastrocnemius reflex after electrical stimulation of sural nerve C-fibres. The effects of SR 48968 were surprisingly weak and may have resulted from an effect of this compound at NK3 receptors.
Houghton
A K
AK
Division of Animal Physiology, School of Biological Sciences, University of Nottingham, Sutton Bonington Campus, Loughhorough, UK.
Ogilvie
J
J
Clarke
R W
RW
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D004558:Electric Stimulation; D005260:Female; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation*; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013497:Sural Nerve / Q000502:physiology
D001549:Benzamides; D010880:Piperidines; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C073839:SR 48968; C091554:SR 142801