Title

Dimished Gastric Prokinetic Response to Ghrelin in a Rat Model of Spinal Cord Injury

Document Type

Article

Publication Date

12-5-2017

Department

Health Sciences

Abstract

Background

Patients with cervical or high-thoracic spinal cord injury (SCI) often present reduced gastric emptying and early satiety. Ghrelin provokes motility via gastric vagal neurocircuitry and ghrelin receptor agonists offer a therapeutic option for gastroparesis. We have previously shown that experimental high-thoracic injury (T3-SCI) diminishes sensitivity to another gastrointestinal peptide, cholecystokinin. This study tests the hypothesis that T3-SCI impairs the vagally mediated response to ghrelin.

Methods

We investigated ghrelin sensitivity in control and T3-SCI rats at 3-days or 3-weeks after injury utilizing: (i) acute (3-day post-injury) fasting and post-prandial serum levels of ghrelin; (ii) in vivo gastric reflex recording following intravenous or central brainstem ghrelin; and (iii) in vitro whole cell recording of neurons within the dorsal motor nucleus of the vagus (DMV).

Key Results

The 2-day food intake of T3-SCI rats was reduced while fasting serum ghrelin levels were higher than in controls. Intravenous and fourth ventricle ghrelin increased in vivo gastric motility in fasted 3-day control rats but not fasted T3-SCI rats. In vitro recording of DMV neurons from 3-day T3-SCI rats were insensitive to exogenous ghrelin. For each measure, vagal responses returned after 3-weeks.

Conclusions and Inferences

Hypophagia accompanying T3-SCI produces a significant and physiologically appropriate elevation in serum ghrelin levels. However, higher ghrelin levels did not translate into increased gastric motility in the acute stage of T3-SCI. We propose that this may reflect diminished sensitivity of peripheral vagal afferents to ghrelin or a reduction in the responsiveness of medullary gastric vagal neurocircuitry following T3-SCI.

Comments

Original version online at http://onlinelibrary.wiley.com/doi/10.1111/nmo.13258/full

DOI

10.1111/nmo.13258

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