title: Anaesthetics differentially modulate the trigeminocardiac reflex excitatory synaptic pathway in the brainstem.
abstract: The trigeminocardiac reflex (TCR) occurs upon excitation of the trigeminal nerve with a resulting bradycardia and hypotension. While several anaesthetics and analgesics have been reported to alter the incidence and strength of the TCR the mechanisms for this modulation are unclear. This study examines the mechanisms of action of ketamine, isoflurane and fentanyl on the synaptic TCR responses in both neurones in the spinal trigeminal interpolaris (Sp5I) nucleus and cardiac vagal neurones (CVNs) in the Nucleus Ambiguus (NA). Stimulation of trigeminal afferent fibres evoked an excitatory postsynaptic current (EPSC) in trigeminal neurones with a latency of 1.8 ± 0.1 ms, jitter of 625 μs, and peak amplitude of 239 ± 45 pA. Synaptic responses further downstream in the reflex pathway in the CVNs occurred with a latency of 12.1 ± 1.1 ms, jitter of 0.8-2 ms and amplitude of 57.8 ± 7.5 pA. The average conduction velocity to the Sp5I neurones was 0.94 ± 0.18 mm ms(-1) indicating a mixture of A-δ and C fibres. Stimulation-evoked EPSCs in both Sp5I and CVNs were completely blocked by AMPA/kainate and NMDA glutamatergic receptor antagonists. Ketamine (10 μm) inhibited the peak amplitude and duration in Sp5I as well as more distal synapses in the CVNs. Isoflurane (300 μm) significantly inhibited, while fentanyl (1 μm) significantly enhanced, EPSC amplitude and area in CVNs but had no effect on the responses in Sp5l neurones. These findings indicate glutamatergic excitatory synaptic pathways are critical in the TCR, and ketamine, isoflurane and fentanyl differentially alter the synaptic pathways via modulation of both AMPA/kainate and NMDA receptors at different synapses in the TCR.
authors.affiliation: Department of Pharmacology and Physiology, and Department of Anesthesiology and Critical Care Medicine, The George Washington University, 2300 Eye Street, NW, Washington, DC 20037, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Christopher
authors.initials: C
authors.lastname: Gorini
authors.forename: Douglas
authors.initials: D
authors.lastname: Sharp
authors.forename: Ryan
authors.initials: R
authors.lastname: Bateman
authors.forename: David
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000187:drug effects* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005283:Fentanyl / Q000494:pharmacology; D006321:Heart / Q000294:innervation; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D059230:Reflex, Trigeminocardiac / Q000187:drug effects* / Q000502:physiology; D014276:Trigeminal Nerve / Q000187:drug effects* / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
chemical_list: D000777:Anesthetics; D007649:Ketamine; D007530:Isoflurane; D005283:Fentanyl; D015742:Propofol