Gastric acid-evoked c-fos messenger RNA expression in rat brainstem is signaled by capsaicin-resistant vagal afferents.
OBJECTIVE
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.
Department of Experimental and Clinical Pharmacology, University of Graz, Graz, Austria.
R
R
Schuligoi
M
M
Jocic
A
A
Heinemann
E
E
Schöninkle
M A
MA
Pabst
P
P
Holzer
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin / Q000633:toxicity*; D005260:Female; D005744:Gastric Acid / Q000502:physiology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D016762:Genes, fos; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000633:toxicity*; D007322:Instillation, Drug; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010146:Pain; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D009270:Naloxone; D009020:Morphine; D006851:Hydrochloric Acid; D002211:Capsaicin