title: NK1-tachykinin receptors and prolonged, stimulus-evoked alterations in the excitability of withdrawal reflexes in the decerebrated and spinalized rabbit.
abstract: Intense natural or electrical stimulation of afferents from the toes or the heel results in prolonged changes in the excitability of the heel withdrawal reflex pathway in the rabbit. This study has investigated the roles played by tachykinin NK1 receptors in mediating these effects. Reflexes were evoked by electrical stimulation of the sural nerve and recorded from the gastrocnemius medialis muscle nerve. High-intensity electrical stimulation of the common peroneal nerve, or application of a crush stimulus to the toes, resulted in suppression of gastrocnemius reflex responses to between 30 and 50% of controls, from which recovery was complete in 15-25 min. In contrast, intense electrical stimulation of the sural nerve, or application of mustard oil to the heel, facilitated the sural to gastrocnemius reflex to two to four times control values. Recovery was rarely complete within 30 min of these stimuli. Administration of the NK1 receptor antagonist CP-96,345, but not its enantiomer CP-96,344, reduced gastrocnemius reflex responses to sural nerve stimulation per se; significantly decreased the time to recovery after common peroneal nerve stimulation and toe crush (but did not affect maximum inhibition); and significantly reduced the facilitation of reflexes resulting from sural nerve stimulation or mustard oil applied to the heel in the first 3-5 min after the application of the stimuli. Both CP-96,345 and CP-96,344 reduced blood pressure and heart rate. These data show that: (i) blockade of NK1-receptors reduces excitatory drive from sural nerve afferents to GM motoneurones; (ii) NK1-receptors are involved in the generation of the early excitatory events which follow stimulation of nociceptive afferents from the heel; and (iii) have a role in the later stages of prolonged, opioid-mediated inhibition of reflexes resulting from activation of fine afferents from the toes. We believe that (ii) and (iii) reflect a role for tachykinins as transmitters from small diameter primary afferent fibres.
authors.affiliation: Department of Physiology and Environmental Science, University of Nottingham, Loughborough, Leicestershire, U.K.
authors.forename: A K
authors.initials: AK
authors.lastname: Houghton
authors.forename: R W
authors.initials: RW
authors.lastname: Clarke
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003655:Decerebrate State; D004558:Electric Stimulation; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation*; D064729:Neurokinin-1 Receptor Antagonists; D010543:Peroneal Nerve / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013497:Sural Nerve / Q000187:drug effects / Q000502:physiology*; D014034:Toes / Q000294:innervation
chemical_list: D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; C066892:CP 96345