期刊论文详细信息
Molecular Pain
Co-induction of cyclooxyenase-2 and early growth response gene (Egr-1) in spinal cord in a clinical model of persistent inflammation and hyperalgesia
Andrea M Nolan1  Claire Crossan2  Peter Hastie1  Sharron Dolan2 
[1] College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ, UK;Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow, G4 0BA, UK
关键词: spinal cord;    cyclooxygenase-2;    Egr-1;    hyperalgesia;    pain;    Inflammation;   
Others  :  865630
DOI  :  10.1186/1744-8069-7-91
 received in 2011-08-11, accepted in 2011-11-23,  发布年份 2011
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【 摘 要 】

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.

【 授权许可】

   
2011 Dolan et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Ley SJ, Livingston A, Waterman AE: The effect of chronic clinical pain on thermal and mechanical thresholds in sheep. Pain 1989, 39:353-357.
  • [2]Dolan S, Kelly JG, Monteiro AM, Nolan AM: Up-regulation of metabotropic glutamate receptor subtypes 3 and 5 in spinal cord in a clinical model of persistent inflammation and hyperalgesia. Pain 2003, 106:501-12.
  • [3]Beveridge WIB: Foot rot in sheep: a transmissible disease due to infection with Fusiformis nodosus (n. sp.): studies on its cause, epidemiology and control. Commonwealth Scientific and Industrial Research Organisation (CSIRO). Australian Bulletin 1941, 140:1-56.
  • [4]Marshall DJ, Walker RI, Cullis BR, Luff MF: The effect of footrot on body weight and wool growth of sheep. Aust Vet J 1991, 68:45-9.
  • [5]Ley SJ, Waterman AE, Livingston A: A field study of the effect of lameness on mechanical nociceptive thresholdsin sheep. Vet Rec 1995, 137:85-7.
  • [6]Malmberg AB, Yaksh TL: Hyperalgesia mediated by spinal glutamate or substance-P receptor blocked by spinal cyclooxygenase inhibition. Science 1992, 257:1276-9.
  • [7]Hay CH, Trevethick MA, Wheeldon A, Bowers JS, DeBelleroche JS: The potential role of spinal cord cyclooxygenase-2 in the development of Freund's complete adjuvant-induced changes in hyperalgesia and allodynia. Neuroscience 1997, 78:843-50.
  • [8]Handy RLC, Moore PK: Effects of selective inhibitors of neuronal nitric oxide synthase on carrageenan-induced mechanical and thermal hyperalgesia. Neuropharmacology 1998, 37:37-43.
  • [9]Dolan S, Nolan AM: N-methyl D-aspartate induced mechanical allodynia is blocked by nitric oxide synthase and cyclooxygenase-2 inhibitors. NeuroReport 1999, 10:449-52.
  • [10]Dolan S, Kelly JG, Huan M, Nolan AM: Transient up-regulation of spinal cyclooxygenase-2 and neuronal nitric oxide synthase following surgical inflammation. Anesthesiol 2003, 98:170-180.
  • [11]Beiche F, Scheuerer S, Brune K, Geisslinger G, Goppelt-Struebe M: Upregulation of cyclooxygenase-2 mRNA in the rat spinal cord following peripheral inflammation. Febs Lett 1996, 390:165-9.
  • [12]Beiche F, Brune K, Geisslinger G, Goppelt-Struebe M: Expression of cyclooxygenase isoforms in the rat spinal cord and their regulation during adjuvant induced arthritis. Inflammation Res 1998, 47:482-7.
  • [13]Ebersberger A, Grubb BD, Willingale HL, Gardiner NJ, Nebe J, Schaible HG: The intraspinal release of prostaglandin E2 in a model of acute arthritis is accompanied by an up-regulation of cyclo-oxygenase-2 in the spinal cord. Neuroscience 1999, 93:775-81.
  • [14]Donaldson LF, Humphrey PS, Oldfield S, Giblett S, Grubb BD: Expression and regulation of prostaglandin E receptor subtype mRNAs in rat sensory ganglia and spinal cord in response to peripheral inflammation. Prostaglandins & Other Lipid Mediators 2001, 63:109-22.
  • [15]Samad TA, Moore KA, Sapirstein A, Billet S, Allchorne A, Poole S, Bonventre JV, Woolf CJ: Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 2001, 410:471-5.
  • [16]Jain NK, Ishikawa TO, Spigelman I, Herschman HR: COX-2 expression and function in the hyperalgesic response to paw inflammation in mice. Prostaglandins Leukot Essent Fatty Acids 2008, 79:183-90.
  • [17]Bozon B, Davis S, Laroche S: A requirement for the immediate early gene zif268 in reconsolidation of recognition memory after retrieval. Neuron 2003, 40:695-701.
  • [18]Davis S, Bozon B, Laroche S: How necessary is the activation of the immediate early gene zif268 in synaptic plasticity and learning? Behav Brain Res 2003, 142:17-30.
  • [19]Cole AJ, Saffen DW, Araban JM, Worley PF: Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature 1989, 340:474-6.
  • [20]Wisden W, Errington ML, Williams S, Dunne SB, Waters C, Hitchcock D, Evans G, Bliss TVP, Hunt SP: Differential expression of immediate early genes in the hippocampus and spinal cord. Neuron 1990, 4:603-14.
  • [21]Rygh LJ, Suzuki R, Rahman W, Wong Y, Vonsy JL, Sandhu H, Webber M, Hunt S, Dickenson AH: Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons. Eur J Neurosci 2006, 24:761-72.
  • [22]Herdegen T, Kovary K, Leah J, Bravo R: Specific temporal and spatial distribution of JUN, FOS, and KROX-24 proteins in spinal neurons following noxious transsynaptic stimulation. J Comp Neurol 1991, 313:178-91.
  • [23]Lantéri-Minet M, de Pommery J, Herdegen T, Weil-Fugazza J, Bravo R, Menétrey D: Differential time course and spatial expression of Fos, Jun, and Krox-24 proteins in spinal cord of rats undergoing subacute or chronic somatic inflammation. J Comp Neurol 1993, 333:223-35.
  • [24]Pertovaara A, Bravo R, Herdegen T: Induction and suppression of immediate-early genes in the rat brain by a selective alpha-2-adrenoreceptor agonist and antagonist following noxious peripheral stimulation. Neuroscience 1993, 54:117-26.
  • [25]Buritova J, Honoré P, Besson JM: Indomethacin reduces both Krox-24 expression in the rat lumbar spinal cord and inflammatory signs following intraplantar carrageenan. Brain Res 1995, 674:211-20.
  • [26]Herdegen T, Riidiger S, Mayer B, Bravo R, Zimmermann M: Expression of nitric oxide synthase and colocalisation with Jun, Fos and Krox transcription factors in spinal cord neurons following noxious stimulation of the rat hindpaw. Mol Brain Res 1994, 22:245-58.
  • [27]Rahman OI, Terayama R, Ikeda T, Koganemaru M, Nakamura T, Shiba R, Nishimori T: Differential effects of NMDA and AMPA/KA receptor antagonists on c-Fos or Zif/268 expression in the rat spinal dorsal horn induced by noxious thermal or mechanical stimulation, or formalin injection. Neurosci Res 2002, 43:389-99.
  • [28]Beckmann AM, Davidson MS, Goodenough S, Wilce PA: Differential expression of Egr-1-like DNA-binding activities in the naive rat brain and after excitatory stimulation. J Neurochem 1997, 69:2227-37.
  • [29]Thiel G, Mayer SI, Müller I, Stefano L, Rössler OG: Egr-1-A Ca(2+)-regulated transcription factor. Cell Calcium 2010, 47:397-403.
  • [30]Latremoliere A, Woolf CJ: Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity. J Pain 2009, 10:895-926.
  • [31]Abbott KA, Lewis CJ: Current approaches to the management of ovine footrot. Vet J 2005, 169:28-41.
  • [32]Kaler J, Daniels SLS, Wright JL, Green LE: Randomised clinical trial of long acting oxytetracycline, foot trimming and flunixine meglumine on time to recovery in sheep with footrot. J Vet Intern Med 2010, 24:420-25.
  • [33]Yamamoto T, Nozaki-Taguchi N: Analysis of the effects of cyclooxygenase (COX)-1 and COX-2 in spinal nociceptive transmission using indomethacin, a non-selective COX inhibitor, and NS-398, a COX-2 selective inhibitor. Brain Res 1996, 739:104-10.
  • [34]Dirig DM, Isakson PC, Yaksh TL: Effect of COX-1 and COX-2 inhibition on induction and maintenance of carrageenan-evoked thermal hyperalgesia in rats. J Pharmacol Exp Ther 1998, 285:1031-38.
  • [35]Yaksh TL, Dirig DM, Conway CM, Svensson C, Luo D, Isakson PC: The acute antihyperalgesic action of non-steroidal, anti-inflammatory drugs and release of spinal PGE2 is mediated by the inhibition of constitutive spinal cyclo-oxygenase-2 (COX-2) but not COX-1. J Neurosci 2001, 21:5847-53.
  • [36]Seybold VS, Jia YP, Abrahams LG: Cyclo-oxygenase-2 contributes to central sensitization in rats with peripheral inflammation. Pain 2003, 105:47-55.
  • [37]Rasley A, Marriott I, Halberstadt CR, Bost KL, Anguita J: Substance P augments Borrelia burgdorferi-induced prostaglandin E2 production by murine microglia. J Immunol 2004, 172:5707-13.
  • [38]Prochazkova M, Dolezal T, Sliva J, Krsiak M: Different patterns of spinal cyclooxygenase-1 and cyclooxygenase-2 mRNA expression in inflammatory and postoperative pain. Basic Clin Pharmacol Toxicol 2006, 99:173-7.
  • [39]Jia YP, Linden DR, Serieb JR, Seybold VS: Nociceptin/orphanin FQ binding increases in superficial laminae of the rat spinal cord during persistent peripheral inflammation. Neurosci Lett 1998, 250:21-24.
  • [40]Zhang YH, Chen Y, Zhao ZQ: Resiniferatoxin reversibly blocks adjuvant-induced thermal hyperalgesia in the rat. Eur J Pharm 2003, 481:301-4.
  • [41]Prochazkova M, Zanvit P, Dolezal T, Prokesova L, Krsiak M: Increased gene expression and production of spinal cyclooxygenase 1 and 2 during experimental osteoarthritis pain. Physiol Res 2009, 58:419-25.
  • [42]Delander GE, Schott E, Brodin E, Fredholm BB: Spinal expression of mRNA for immediate early genes in a model of chronic pain. Acta Physiol Scand 1997, 161:517-25.
  • [43]Ko SW, Vadakkan KI, Ao H, Gallitano-Mendel A, Wei F, Milbrandt J, Zhuo M: Selective contribution of Egr1 (zif/268) to persistent inflammatory pain. J Pain 2005, 6:12-20.
  • [44]Murakami M, Kudo I: Prostaglandin E Synthase: A Novel Drug Target for Inflammation and Cancer. Curr Pharmaceut Des 2006, 12:943-54.
  • [45]Díaz-Muñoz MD, Osma-García IC, Cacheiro-Llaguno C, Fresno M, Íñiguez MA: Coordinated up-regulation of cyclooxygenase-2 and microsomal prostaglandin E synthase 1 transcription by nuclear factor kappa B and early growth response-1 in macrophages. Cell Signal 2010, 22:1427-36.
  • [46]Ngiam N, Peltekova V, Engelberts D, Otulakowski G, Post M, Kavanagh BP: Early growth response-1 worsens ventilator-induced lung injury by up-regulating prostanoid synthesis. Am J Respir Crit Care Med 2010, 181:947-56.
  • [47]Szabó IL, Pai R, Soreghan B, Jones MK, Baatar D, Kawanaka H, Tarnawski AS: NSAIDs inhibit the activation of egr-1 gene in microvascular endothelial cells. A key to inhibition of angiogenesis? J Physiol Paris 2001, 95:379-83.
  • [48]Pham L, Bezouglaia O, Camargo PM, Nervina JM, Tetradis S: Prostanoids induce egr1 gene expression in cementoblastic OCCM cells. J Periodontal Res 2007, 42:486-93.
  • [49]Welsh EM, Gettinby G, Nolan AM: Comparison of a visual analogue scale and a numerical rating scale for assessment of lameness, using sheep as a model. Am J Vet Res 1993, 54:976-83.
  • [50]Nolan A, Livingston A, Morris R, Waterman A: Techniques for comparison of thermal and mechanical nociceptive stimuli in the sheep. J Pharmacol Meth 1987, 17:39-49.
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