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 vagal muscarinic pathways. In rats, the increase in gastric mucosal blood flow evoked by a low ic dose of RX 77368 occurs via release of calcitonin gene-related peptide from capsaicin-sensitive afferent neurons, most probably of spinal origin. In this study, the effect of low ic doses of RX 77368 on afferent impulse activity in splanchnic single fibers was investigated. The cisterna magna of overnight-fasted, urethan-anesthetized Sprague-Dawley rats was acutely cannulated, and fine splanchnic nerve twigs containing at least one fiber responsive to mechanical probing of the stomach were isolated at a site immediately distal to the left suprarenal ganglion. Unit mechanoreceptive fields were encountered in all portions of the stomach, both superficially and in deeper layers. Splanchnic afferent unit impulse activity was recorded continuously during basal conditions and in response to consecutive ic injections of saline and RX 77368 (15-30 min later; 1.5 or 3 ng). Basal discharge rates ranged from 0 to 154 impulses/min (median = 10.2 impulses/min). A majority of splanchnic single units with ongoing activity increased their mean discharge rate by >/=20% after ic injection of RX 77368 at either 1.5 ng (6/10 units; median increase 63%) or 3 ng (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 was followed by a decline to stable activity levels </=20-40 min thereafter. In a few cases (4/24), ic RX 77368 (3 ng) inhibited the impulse activity of initially active units, with a time course comparable to that seen in units excited by the same treatment. The pattern of discharge in most units was not suggestive of mechanical modulation of activity by rhythmic gastric contractions. The data demonstrate that low ic doses of TRH analogue induce sustained increases in afferent discharge in a substantial proportion of splanchnic neurons innervating the rat stomach. These findings support the notion that splanchnic afferent excitation occurs concomitantly with vasodilatory peptide release from gastric splanchnic afferent nerve terminals after ic TRH-induced autonomic activation.