Vagal afferent input from the acid-challenged rat stomach to the brainstem:: Enhancement by interleukin-1β

Exposure of the gastric mucosa to back-diffusing concentrations of HCI (0.25 M, pH 0.51) stimulates vagal afferent input to the brainstem. Here we have examined whether pretreatment of rats with the proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha causes sensitization of vagal afferent pathways to HCI. Rats were pretreated i.p. with interleukin-1beta, tumor necrosis factor-alpha (10 mug/kg) or their vehicle (sterile saline) 24, 48 and 96 h before intragastric administration of HCI (0.25 M, 1 m1/100 g). Activation of neurons in the nucleus tractus solitarii was visualized by c-Fos immunohistochemistry 2 h after the HCI challenge. I.p. administration of interleukin-1beta and tumor necrosis factor-alpha alone induced c-Fos in the brainstem, an effect that was gone after 24 h. At this time, however, the effect of HCI to cause expression of c-Fos in the nucleus tractus solitarii was significantly enhanced by pretreatment with interleukin-1beta and tumor necrosis factor-alpha. The sensitizing effect of i.p.-administered interleukin-1beta was sustained for more than 48 h and prevented by the interleukin-1 receptor antagonist anakinra. Intracisternal administration of interleukin-1beta and tumor necrosis factor-alpha (100 ng) failed to amplify the HCI-evoked expression of c-Fos in the brainstem. These results show that peripheral administration of the proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha induces prolonged sensitization of vagal afferent pathways to gastric HCI challenge. This effect seems to arise from a peripheral action on vagal afferents and may be of relevance to gastric chemonociception. 2004 Published by Elsevier Ltd on behalf of IBRO.