Central autonomic activation by intracisternal TRH analogue excites gastric splanchnic afferent neurons

Intracisternal (ic) injection of thyrotropin-releasing hormone (TRH) or its stable analogue RX 77368 influences gastric function via stimulation of va gal muscarinic pathways. In rats, the increase in gastric mucosal blood flo w evoked by a low ic dose of RX 77368 occurs via release of calcitonin gene -related peptide from capsaicin-sensitive afferent neurons, most probably o f spinal origin. In this study, the effect of low ic doses of RX 77368 on a fferent impulse activity in splanchnic single fibers was investigated. The cisterna magna of overnight-fasted, urethan-anesthetized Sprague-Dawley rat s was acutely cannulated, and fine splanchnic nerve twigs containing at lea st one fiber responsive to mechanical probing of the stomach were isolated at a site immediately distal to the left suprarenal ganglion. Unit mechanor eceptive fields were encountered in all portions of the stomach, both super ficially and in deeper layers. Splanchnic afferent unit impulse activity wa s recorded continuously during basal conditions and in response to consecut ive ic;injections of saline and RX 77368 (15-30 min later; 1.5 or 3 ng). Ba sal discharge rates ranged from 0 to 154 impulses/min (median = 10.2 impuls es/min). A majority of splanchnic single units with ongoing activity increa sed their mean discharge rate by greater than or equal to 20% after ic inje ction of RX 77368 at either 1.5 ng (6/10 units; median increase 63%) or 3 n g (19/24 units; median increase 175%). Five units lacking impulse activity in the 5-min before ic RX 77368 (3 ng) were also excited, with the onset of discharge occurring within 1.0-5.0 min postinjection. In units excited by ic RX 77368, peak discharge occurred 15.6 +/- 1.3 min after injection and w as followed by a decline to stable activity levels less than or equal to 20 -40 min thereafter. Tn a few cases (4/24), ic RX 77368(3 ng) inhibited the impulse activity of initially active units, with a time course comparable t o that seen in units excited by the same treatment. The pattern of discharg e in most units was not suggestive of mechanical modulation of activity by rhythmic gastric contractions. The data demonstrate that low ic doses of TR H analogue induce sustained increases in afferent discharge in a substantia l proportion of splanchnic neurons innervating the rat stomach. These findi ngs support the notion that splanchnic afferent excitation occurs concomita ntly with vasodilatory peptide release from gastric splanchnic afferent ner ve terminals after ic TRH-induced autonomic activation.