Investigations into the role of substance P and the NK-1 receptor in an animal model of neuropathic pain

Abstract

This study investigates the role of substance P and NK-1 receptors in an animal model of neuropathic pain. Unlike naive animals, innocuous peripheral stimulation of neuropathic animals was determined to cause heterosegmental inhibition in the tail-flick test as well as increased plasma extravasation in the paw. These effects were prevented by administration of CP-96,345 before stimulation. Additionally, CP-96,345 or an antisense oligonucleotide against NK-1 receptors significantly alleviated mechanical allodynia in neuropathic animals. Finally, mass spectrum of lumbar spinal cord of neuropathic but not naIve animals showed a significant upregulation of substance P. We conclude that innocuous stimulation of a neuropathic area could trigger activation of NK-1 receptors, presumably due to binding of substance P. Furthermore, this activation of NK-1 receptors could be central to the perception of mechanical allodynia in neuropathic pain. These results justify the investigation of inhibiting the interaction between substance P and the NK-1 receptor for the treatment of drug resistant neuropathies