Gastric acid-evoked c-fos messenger RNA expression in rat brainstem is signaled by capsaicin-resistant vagal afferents

Gastroenterology. 1998 Sep;115(3):649-60. doi: 10.1016/s0016-5085(98)70144-1.


Background & aims: Gastric acid is known to contribute to ulcer pain, but the mechanisms of gastric chemonociception are poorly understood. This study set out to investigate the pathways and mechanisms by which gastric acid challenge is signaled to the brain.

Methods: Neuronal excitation in the rat brainstem and spinal cord after intragastric administration of HCl (0.35-0.7 mol/L) was examined by in situ hybridization autoradiography for the immediate early gene c-fos.

Results: Gastric acid challenge did not induce c-fos transcription in the spinal cord but caused many neurons in the nucleus tractus solitarii and area postrema to express c-fos messenger RNA (mRNA). The HCl concentration-dependent excitation of medullary neurons was in part associated with behavioral manifestations of pain but not directly related to the acid-induced injury and contraction of the stomach. Subdiaphragmatic vagotomy suppressed the c-fos mRNA response to intragastric acid, and morphine inhibited it in a naloxone-reversible manner, whereas pretreatment of rats with capsaicin was without effect.

Conclusions: Gastric acid challenge is signaled to the brainstem, but not the spinal cord, through vagal afferents that are sensitive to acid but resistant to capsaicin. It is hypothesized that the gastric acid-induced c-fos transcription in the brainstem is related to gastric chemonociception.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / physiology
  • Animals
  • Brain Stem / drug effects
  • Brain Stem / physiology*
  • Capsaicin / toxicity*
  • Female
  • Gastric Acid / physiology*
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / pathology*
  • Gastric Mucosa / physiology
  • Genes, fos*
  • Hydrochloric Acid / administration & dosage
  • Hydrochloric Acid / toxicity*
  • Instillation, Drug
  • Morphine / pharmacology
  • Naloxone / pharmacology
  • Pain
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Skin
  • Spinal Cord / drug effects
  • Spinal Cord / physiology*
  • Transcription, Genetic* / drug effects
  • Vagus Nerve / drug effects
  • Vagus Nerve / physiology*


  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Naloxone
  • Morphine
  • Hydrochloric Acid
  • Capsaicin