Differential c-Fos expression in the nucleus of the solitary tract and spinal cord following noxious gastric distention in the rat

doi:10.1016/0306-4522(96)00173-X

Neuroscience

Volume 74, Issue 3, 2 August 1996, Pages 873-884

https://doi.org/10.1016/0306-4522(96)00173-X Get rights and content

Abstract

c-Fos has been used as a marker for activity in the spinal cord following noxious somatic or visceral stimulation. Although the viscera receive dual afferent innervation, distention of hollow organs (i.e. esophagus, stomach, descending colon and rectum) induces significantly more c-Fos in second order neurons in the nucleus of the solitary tract and lumbosacral spinal cord, which receive parasympathetic afferent input (vagus, pelvic nerves), than the thoracolumbar spinal cord, which receives sympathetic afferent input (splanchnic nerves). The purpose of this study was to determine the contribution of sympathetic and parasympathetic afferent input to c-Fos expression in the nucleus of the solitary tract and spinal cord, and the influence of supraspinal pathways on Fos induction in the thoracolumbar spinal cord. Noxious gastric distention to 80 mmHg (gastric distension/80) was produced by repetitive inflation of a chronically implanted gastric balloon. Gastric distension/80 induced c-Fos throughout the nucleus of the solitary tract, with the densest labeling observed within 300 μm of the rostral pole of the area postrema. This area was analysed quantitatively following several manipulations. Gastric distension/80 induced a mean of 724 c-Fos-immunoreactive nuclei per section. Following subdiaphragmatic vagotomy plus distention (vagotomy/80), the induction of c-Fos-immunoreactive nuclei was reduced to 293 per section, while spinal transection at T2 plus distention (spinal transection/80) induced a mean of 581 nuclei per nucleus of the solitary tract section. Gastric distension/80 and vagotomy/80 induced minimal c-Fos in the T8–T10 spinal cord (50 nuclei/section), but spinal transection/80 induced 200 nuclei per section. Repetitive bolus injections of norepinephrine produced transient pressor responses mimicking the pressor response produced by gastric distension/80. This manipulation induced minimal c-Fos in the nucleus of the solitary tract and none in the spinal cord.

It is concluded that noxious visceral input via parasympathetic vagal afferents, and to a lesser extent sympathetic afferents and the spinosolitary tract, contribute to gastric distention-induced c-Fos in the nucleus of the solitary tract. The induction of c-Fos in the nucleus of the solitary tract is significantly greater than in the viscerotopic segments of the spinal cord, which is partially under tonic descending inhibition, but is not subject to modulation by vagal gastric afferents. Distention pressures produced by noxious gastric distention are much greater than those produced during feeding, suggesting that c-Fos induction in the nucleus of the solitary tract to noxious distention is not associated with physiological mechanisms of feeding and satiety.

The large vagal nerve-mediated induction of c-Fos in the nucleus of the solitary tract following gastric distension suggests that parasympathetic afferents contribute to the processing of noxious visceral stimuli, perhaps by contributing to the affective–emotional component of visceral pain.

Section snippets

Surgical procedures

All protocols were approved by the University of Iowa Animal Care and Use Committee. Three surgical procedures were used. Male Sprague–Dawley rats (350–450 g; Harlan, Indianapolis, IN, U.S.A.) were anesthetized with pentobarbital sodium (50 mg/kg, i.p.) and a 2–3-cm-long latex balloon attached to polyethylene tubing (PE-240) was surgically implanted in the stomach through the fundus. The tubing was exteriorized at the back of the neck. One group of rats (gastric distension) did not undergo any

Nucleus of the solitary tract

Noxious gastric distention/80 produced a marked induction of c-Fos in the NTS and the dorsal motor nucleus of the vagus (hereafter included in the NTS counts; Fig. 1, Fig. 4, Fig. 5a). Stained nuclei were observed along the rostrocaudal extent of the NTS from several hundred micrometers caudal to the obex to several hundred micrometers rostral to the area postrema. Staining was most dense immediately rostral to the area postrema (300–400 stained nuclei per side per section). There was a

Discussion

Primary afferents in the vagus and pelvic nerves that innervate the viscera have been termed parasympathetic afferents because they project in the same nerves as parasympathetic efferents. Likewise, spinal afferents of thoracolumbar origin that innervate the viscera and project in the same nerves as sympathetic efferents have been termed sympathetic afferents. Repetitive distention of the stomach to 80 mmHg pressure is a noxious stimulus.[50]In this context, the present results confirm previous

Conclusion

Noxious gastric distension induces considerable c-Fos in the NTS. Gastric vagal afferents comprise the majority of the afferent input, although sympathetic afferent–spinosolitary tract input is present. Noxious gastric distension induces much less c-Fos in the spinal cord, and the expression is subject to tonic descending modulation. The present results support the hypothesis that parasympathetic afferents convey nociceptive information which may contribute to the emotional–affective component

Acknowledgements

We thank Dr Ana Solodkin for comments on the manuscript. This work was supported by NS 30604 and NS 19912.

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