Nerve growth factor and gastric hyperalgesia in the rat.

Abstract

We recently demonstrated an association between the development of hyperalgesia and an increase in nerve growth factor (NGF) during gastric inflammation. We hypothesized that block of NGF signalling will blunt injury-induced hyperalgesia. Male Sprague-Dawley rats (300-400 g) were anaesthetized, the stomach was exposed and placed in a circular clamp. Acetic acid (60%) or saline (control) was injected into this area and aspirated 45 s later, resulting in kissing ulcers. A balloon was surgically placed into the stomach and electromyographic responses to gastric distension (GD) were recorded from the acromiotrapezius muscle. Animals received a daily injection of neutralizing NGF antibody or control serum for 5 days. NGF in the stomach wall was measured with an ELISA. The severity of gastric injury was assessed macroscopically and by determination of myeloperoxidase (MPO) activity. Gastric injury enhanced the visceromotor response to GD and increased NGF content. Anti-NGF significantly blunted the development of hyperalgesia and led to a decrease in gastric wall thickness and MPO activity. Increases in NGF contribute to the development of hyperalgesia after gastric injury. This may be partly mediated by direct effects on afferent nerves and indirectly by modulatory effects on the inflammatory response.