Up-regulation 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) Up-regulation 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)

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Publisher's URL: http://dx.doi.org/10.1523/JNEUROSCI.5401-06.2007

Abstract

It has been proposed that substance P and calcitonin gene-related peptide (CGRP) are up-regulated in low-threshold myelinated primary afferents following 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 internalisation in the dorsal horn following 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 to SNT. In addition, we did not detect any Aβ-evoked NK1 receptor internalisation in neurons from laminae 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, Dr John
Authors: Hughes, D.I., Scott, D.T., Riddell, J.S., and Todd, A.J.
Subjects:R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Journal of Neuroscience
ISSN:0270-6474

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