A natural peptide with NMDA inhibitory activity reduces tonic pain in the formalin model

The aim of this study was to assess whether a natural peptide, histogranin, isolated from chromaffin cells and possessing NMDA receptor inhibitory activity, could reduce tonic pain. Rats received intrathecal injections of the stable analog [Ser1]histogranin (SHG), prior to induction of the formalin response. SHG markedly suppressed the second tonic phase of the formalin response compared with saline vehicle. A U-shaped dose-response curve was obtained. SHG had no effect on phase 1 acute pain responses. These findings indicate that SHG acts in a similar fashion as other, non-peptide, NMDA antagonists in suppressing tonic, but not acute pain. The presence of the natural peptide in chromaffin cells may contribute to the analgesic effects of adrenal medullary implants.