Co-induction of cyclooxyenase-2 and early growth response gene (<it>Egr-1</it>) in spinal cord in a clinical model of persistent inflammation and hyperalgesia

• Main Authors: Dolan Sharron (Author), Hastie Peter (Author), Crossan Claire (Author), Nolan Andrea M (Author)
• Format: Book
• Published: SAGE Publishing, 2011-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/1744-8069-7-91; 1744-8069
• Keywords: Inflammation; pain; hyperalgesia; Egr-1; cyclooxygenase-2; spinal cord; Pathology; RB1-214
• Source: Molecular Pain, Vol 7, Iss 1, p 91 (2011)

<p>Abstract</p> <p>Background</p> <p>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 (<it>Egr-1</it>), 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 <it>Egr-1 </it>mRNA and protein were analysed using real-time PCR and Western blotting.</p> <p>Results</p> <p>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 <it>Egr-1 </it>mRNA and protein were observed in spinal cord from lame animals. Three days after treatment, levels of <it>Egr-1 </it>mRNA returned to control levels, however, <it>Egr-1 </it>protein remained elevated.</p> <p>Conclusion</p> <p>Elevated levels of spinal COX-2 and <it>Egr-1 </it>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.</p>