Differential expression of c-fos messenger RNA in the rat spinal cord after mucosal and serosal irritation of the stomach.

Expression of the immediate early gene c-fos is considered to be a marker for neuronal activation in the spinal cord in response to afferent input. Since the stomach is continually exposed to injurious chemicals, the present study examined whether application of acid (0.15 M HCl) and formalin (5%) to the gastric mucosa or serosal surface of the stomach stimulates c-fos transcription in the caudal thoracic spinal cord of anaesthetized rats. The spinal cord was removed 15, 45 or 120 min after exposure of the stomach to the noxious chemicals and processed for quantitative in situ hybridization autoradiography of c-fos messenger RNA. Exposure of the gastric mucosa to acid or formalin failed to increase the expression of c-fos messenger RNA in the thoracic spinal cord. Application of acid to the serosal surface of the stomach was also unable to stimulate c-fos transcription, whereas serosal application of formalin led to substantial expression of c-fos messenger RNA in the superficial but also deeper laminae of the spinal dorsal horn when examined 45 min, but not 15 or 120 min, post-stimulation. The highest expression of c-fos messenger RNA was seen when formalin was injected subcutaneously into one hindpaw and c-fos transcription was examined in the lumbar spinal cord. These data indicate that acute exposure of the gastric mucosa to chemical injury does not provide the afferent input which is necessary to cause appreciable c-fos transcription in second order neurons within the spinal cord. Stimulation of the gastric mucosa by acid and formalin was followed, however, by gastric hyperaemia in which spinal afferents releasing vasodilator peptides have been implicated. It is concluded, therefore, that acute stimulation of nociceptive afferents in the stomach causes local homoeostatic reactions but does not necessarily provide afferent input sufficient to recruit spinal nociceptive circuits.