Upregulation of substance P in low-threshold myelinated afferents is not required for tactile allodynia in the chronic constriction injury and spinal nerve ligation models

Hughes, D.I. , Scott, D.T., Riddell, J.S. and Todd, A.J. (2007) Upregulation of substance P in low-threshold myelinated afferents is not required for tactile allodynia in the chronic constriction injury and spinal nerve ligation models. Journal of Neuroscience, 27(8), pp. 2035-2044. (doi: 10.1523/JNEUROSCI.5401-06.2007)

Abstract

It has been proposed that substance P and calcitonin gene-related peptide (CGRP) are upregulated in low-threshold myelinated primary afferents after certain types of nerve injury, and that release of substance P from these afferents contributes to the resulting tactile allodynia. To test this hypothesis, we looked for neuropeptides in Aβ primary afferent terminals in the ipsilateral gracile nucleus and spinal dorsal horn in three nerve injury models: sciatic nerve transection (SNT), spinal nerve ligation (SNL), and chronic constriction injury (CCI). We also looked for evidence of neurokinin 1 (NK1) receptor internalization in the dorsal horn after electrical stimulation of Aβ afferents. We found no evidence of either substance P or CGRP expression in injured Aβ terminals in the spinal cord in any of the models. Although substance P was not detected in terminals of injured afferents in the gracile nucleus, CGRP was expressed in between 32 and 68% of these terminals, with a significantly higher proportion in the SNL and CCI models, compared with SNT. In addition, we did not detect any Aβ-evoked NK1 receptor internalization in neurons from laminas I, III, or IV of the dorsal horn in the CCI or SNL models. These results do not support the proposal that substance P is present at significant levels in the terminals of injured Aβ primary afferents in neuropathic models. They also suggest that any release of substance P from injured Aβ afferents is unlikely to activate NK1 receptors in the dorsal horn or contribute to neuropathic pain.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hughes, Dr David I and Todd, Professor Andrew and Riddell, Professor John
• Authors: Hughes, D.I., Scott, D.T., Riddell, J.S., and Todd, A.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Journal of Neuroscience
• ISSN: 0270-6474
• ISSN (Online): 1529-2401
• Copyright Holders: Copyright © 2007 Society for Neuroscience
• First Published: First published in Journal of Neuroscience 27(8):2035-2044
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher