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Descending controls modulate inflammatory joint pain and regulate CXC chemokine and iNOS expression in the dorsal horn

Fiona B Carr, Sandrine M Géranton and Stephen P Hunt*

Author Affiliations

Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK

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Molecular Pain 2014, 10:39  doi:10.1186/1744-8069-10-39

Published: 20 June 2014

Abstract

Background

Descending control of nociceptive processing, by pathways originating in the rostral ventromedial medulla (RVM) and terminating in the dorsal horn, contributes to behavioural hypersensitivity in a number of pain models. Two facilitatory pathways have been identified and are characterized by serotonin (5-HT) content or expression of the mu opiate receptor. Here we investigated the contribution of these pathways to inflammatory joint pain behaviour and gene expression changes in the dorsal horn.

Results

Selective lesion of the descending serotonergic (5-HT) pathway by prior intrathecal administration of 5,7-dihydroxytryptamine attenuated hypersensitivity at early time points following ankle injection of CFA. In a separate study ablation of the mu opioid receptor expressing (MOR+) cells of the RVM, by microinjection of the toxin dermorphin-saporin, resulted in a more prolonged attenuation of hypersensitivity post CFA. Microarray analysis was carried out to identify changes in dorsal horn gene expression associated with descending facilitation by the MOR+ pathway at 7d post joint inflammation. This analysis led to the identification of a number of genes including the chemokines Cxcl9 and Cxcl10, their common receptor Cxcr3, and the proinflammatory gene Nos2 (inducible nitric oxide synthase, iNOS).

Conclusions

These findings demonstrate that joint pain behaviour is dependent in part on descending facilitation via the RVM, and identify a novel pathway driving CXC chemokine and iNOS expression in the dorsal horn.

Keywords:
RVM; Joint pain; 5-HT; Mu opioid receptor; CXCL9; CXCL10; iNOS; CXCR3