Co-Induction of Cyclooxyenase-2 and Early Growth Response Gene (Egr-1) in Spinal Cord in a Clinical Model of Persistent Inflammation and Hyperalgesia. Issue 1 (23rd November 2011)

• Record Type: Journal Article
• Authors: Dolan, Sharron; Hastie, Peter; Crossan, Claire; Nolan, Andrea M
• Is Part Of: Molecular pain. Volume 7:Issue 1(2011)
• Publication Date: 2011-11-23
• Subjects: Inflammation -- pain -- hyperalgesia -- Egr-1 -- cyclooxygenase-2 -- spinal cord; Pain -- Molecular aspects -- Periodicals; Pain -- Pathophysiology -- Periodicals; Pain -- Physiological aspects -- Periodicals; 616.0472
• DOI: 10.1186/1744-8069-7-91
• Languages: English
• ISSNs: 1744-8069

Abstract

Background: This study characterised the effects of persistent peripheral inflammation of the foot on pain and spinal cord expression of cyclooxygenase-1 and −2 (COX-1 and COX-2) and early growth response gene 1 (Egr-1), known markers of neuronal plasticity, in a clinical model of naturally-occurring inflammatory disease and hyperalgesia in sheep ('footrot'), before and after routine treatment (parenteral treatment with antibiotics and antiseptic footbathing). The temporal pattern of expression of COX-1, COX-2 and Egr-1 mRNA and protein were analysed using real-time PCR and Western blotting. Results: Animals affected with persistent peripheral inflammation displayed significant hyperalgesia and lameness (a proxy indicator of spontaneous pain) restricted to the inflamed limb. Hyperalgesia and lameness were significantly attenuated 1 day after treatment, and resolved further by day 7 and day 3, respectively. COX-2 but not COX-1, protein expression was up-regulated in spinal cord from lame animals on day 0, before treatment. Following treatment and attenuation of pain behaviours, levels of COX-2 returned to control levels. Significant induction of Egr-1 mRNA and protein were observed in spinal cord from lame animals. Three days after treatment, levels of Egr-1 mRNA returned to control levels, however, Egr-1 protein remained elevated. Conclusion: Elevated levels of spinal COX-2 and Egr-1 protein correlate with the presence of pain and hyperalgesia, and may underlie persistent pain, although a direct causal link has still to be established. Understanding the temporal pattern of expression of key mediators in clinical pain states may lead to better strategies to manage pain.