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

Dolan, S., Hastie, P. , Crossan, C. and Nolan, A.M. (2011) Co-induction of cyclooxyenase-2 and early growth response gene (Egr-1) in spinal cord in a clinical model of persistent inflammation and hyperalgesia. Molecular Pain, 7, p. 91. (doi: 10.1186/1744-8069-7-91) (PMID:22112635) (PMCID:PMC3256114)

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Abstract

<p><b>BACKGROUND:</b> 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.</p> <p><b>RESULTS:</b> 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.</p> <p><b>CONCLUSION:</b> 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.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hastie, Professor Peter and Crossan, Miss Claire and Nolan, Professor Andrea
Authors: Dolan, S., Hastie, P., Crossan, C., and Nolan, A.M.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Molecular Pain
Publisher:BioMed Central
ISSN:1744-8069
ISSN (Online):1744-8069
Published Online:23 November 2011

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
352541Characterisation of the role of metabotropic glutamate receptors in persistent inflammatory pain and hyperalgesiaAndrea NolanBiotechnology and Biological Sciences Research Council (BBSRC)S19801Senior Vice Principal