GASTRIC ACID-EVOKED C-FOS MESSENGER-RNA EXPRESSION IN RAT BRAIN-STEM IS SIGNALED BY CAPSAICIN-RESISTANT VAGAL AFFERENTS

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 ex citation in the rat brainstem and spinal cord after intragastric admin istration of HCl (0.35-0.7 mol/L) was examined by in situ hybridizatio n 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 post rema to express c-fos messenger RNA (mRNA). The HCl concentration-depe ndent excitation of medullary neurons was in part associated with beha vioral manifestations of pain but not directly related to the acid-ind uced 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 chal lenge is signaled to the brainstem, but not the spinal cord, through v agal afferents that are sensitive to acid but resistant to capsaicin. It is hypothesized that the gastric acid-induced c-fos transcription i n the brainstem is related to gastric chemonociception.