title: Somatic nociception activates NK1 receptors in the nucleus tractus solitarii to attenuate the baroreceptor cardiac reflex.
abstract: There is limited information regarding the integration of visceral and somatic afferents within the nucleus of the solitary tract (NTS). We studied the interaction of nociceptive and baroreceptive inputs in this nucleus in an in situ arterially perfused, un-anaesthetized decerebrate preparation of rat. At the systemic level, the gain of the cardiac component of the baroreceptor reflex was attenuated significantly by noxious mechanical stimulation of a forepaw. This baroreceptor reflex depression was mimicked by NTS microinjection of substance P and antagonized by microinjection of either bicuculline (a GABAA receptor antagonist) or a neurokinin type 1 (NK1) receptor antagonist (CP-99994). The substance P effect was also blocked by a bilateral microinjection of bicuculline, at a dose that was without effect on basal baroreceptor reflex gain. Baroreceptive NTS neurons were defined by their excitatory response following increases in pressure within the ipsilateral carotid sinus. In 27 of 34 neurons the number of evoked spikes from baroreceptor stimulation was reduced significantly by concomitant electrical stimulation of the brachial nerve (P < 0.01). Furthermore, the attenuation of baroreceptor inputs to NTS neurons by brachial nerve stimulation was prevented by pressure-ejection of bicuculline from a multi-barrelled microelectrode (n = 8). In a separate population of 17 of 45 cells tested, brachial nerve stimulation evoked an excitatory response that was antagonized by blockade of NK1 receptors. We conclude that nociceptive afferents activate NK1 receptors, which in turn excite GABAergic interneurons impinging on cells mediating the cardiac component of the baroreceptor reflex.
authors.affiliation: Department of Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK. P.Boscan@bristol.ac.uk
authors.forename: Pedro
authors.initials: P
authors.lastname: Boscan
authors.forename: Sergey
authors.initials: S
authors.lastname: Kasparov
authors.forename: Julian F R
authors.initials: JF
authors.lastname: Paton
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D008845:Microinjections; D009433:Neural Inhibition; D064729:Neurokinin-1 Receptor Antagonists; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain; D010147:Pain Measurement; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D017552:Solitary Nucleus / Q000378:metabolism / Q000503:physiopathology*; D013373:Substance P / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018756:GABA Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011963:Receptors, GABA-A; D018040:Receptors, Neurokinin-1; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline