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

作者：Carr Fiona B; Geranton Sandrine M; Hunt Stephen P^*

来源：Molecular Pain, 2014, 10: 39.

DOI：10.1186/1744-8069-10-39

• RVM
• Joint pain
• 5-HT
• Mu opioid receptor
• CXCL9
• CXCL10
• iNOS
• CXCR3

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.

• 出版日期2014-6-20