Carr F, Géranton SM, Hunt SP (2012) Descending facilitation contributes to changes in dorsal horn gene expression in a rat model of inflammatory joint pain. Neuroscience 2012 Abstracts 785.07. Society for Neuroscience, New Orleans, LA.
Summary: Chronic pain is associated with increased excitability and changes in gene expression within the dorsal horn. Descending facilitation from the rostral ventromedial medulla (RVM) is known to contribute to this excitability and behavioural hypersensitivity in a number of pain states. This would suggest that some of the gene changes associated with chronic pain could be driven by descending pathways terminating in the dorsal horn. We have previously demonstrated that ablation of a subset of RVM neurons expressing the mu opioid receptor (MOR) attenuates behavioural hypersensitivity following joint inflammation. The aim of the present study was to combine lesion of the RVM with microarray analysis of the dorsal horn to identify genes regulated by descending facilitation in this pain model. Selective lesion of MOR expressing cells of the RVM was carried out in rats by microinjection of the selective toxin dermorphin-saporin. Non-lesioned controls received vehicle microinjection. 4 weeks after the lesion procedure when depletion of the MOR+ cells was complete, both groups received an injection of 10μl Complete Freund’s Adjuvant to the left ankle joint. 7 days later the animals were sacrificed and the ipsilateral quadrant of the dorsal horn of the spinal cord lumbar region (L4-L6) removed. RNA was extracted and microarray analysis carried out using Affymetrix GeneChip Rat Gene 1.0 ST Arrays. Raw data was analysed in R using Bioconductor open source software. Limma testing was applied and a list of genes differentially regulated in animals with prior RVM lesion compared to non-lesioned controls was generated. The majority of differentially regulated genes (73%) were downregulated in the lesioned group. We used the DAVID bioinformatics resource to cluster the genes into groups with similar functional annotations (Huang et al., 2009). This analysis identified 16 gene clusters with significantly enriched functional annotations. Among these enriched functions were ribosomal function and biogenesis, inflammatory response (including the chemokine CXCL10), GPCR signalling (including the serotonin receptor 5HTR1D) and transcriptional regulation (including the transcriptional repressor RCOR2). Following on from identification of functional categories, validation of genes of interest was carried out using RT-qPCR. Our findings suggest that descending facilitation contributes to gene expression changes within the dorsal horn and that this may correlate with behavioural hypersensitivity observed in chronic pain.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)