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

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.

• Authors: Fiona B Carr, Sandrine M Géranton, Stephen P Hunt
• Journal: Molecular pain (Mol Pain) Vol. 10 Pg. 39 (Jun 20 2014) ISSN: 1744-8069 [Electronic] United States
• PMID: 24947159 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines, CXC
• Opioid Peptides
• Ribosome Inactivating Proteins, Type 1
• Serotonin Agents
• dermorphin-saporin
• 5,7-Dihydroxytryptamine
• Nitric Oxide Synthase Type II
• Saporins

Topics

• 5,7-Dihydroxytryptamine (therapeutic use)
• Animals
• Arthritis (chemically induced, complications)
• Chemokines, CXC (genetics, metabolism)
• Disease Models, Animal
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Hyperalgesia (drug therapy, etiology)
• Male
• Medulla Oblongata (drug effects, physiology)
• Neural Pathways (physiology)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Opioid Peptides (pharmacology)
• Pain (etiology, pathology)
• Pain Threshold (drug effects)
• Posterior Horn Cells (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Ribosome Inactivating Proteins, Type 1 (pharmacology)
• Saporins
• Serotonin Agents (therapeutic use)
• Spinal Cord (pathology)