期刊论文详细信息
Molecular Pain
Preclinical studies of low back pain
Jun-Ming Zhang1  Feguens J Bataille1  Wenrui Xie1  Judith A Strong1 
[1] Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0531, USA
关键词: Glucocorticoid receptor;    Mineralocorticoid receptor;    Eplerenone;    Cxcl1;    IL1-β;    MCP-1;    TNF-α;    Spontaneous activity;    Sensory ganglia;   
Others  :  862537
DOI  :  10.1186/1744-8069-9-17
 received in 2013-01-07, accepted in 2013-03-18,  发布年份 2013
PDF
【 摘 要 】

Chronic low back pain is a major cause of disability and health care costs. Current treatments are inadequate for many patients. A number of preclinical models have been developed that attempt to mimic aspects of clinical conditions that contribute to low back pain. These involve application of nucleus pulposus material near the lumbar dorsal root ganglia (DRG), chronic compression of the DRG, or localized inflammation of the DRG. These models, which are primarily implemented in rats, have many common features including behavioral hypersensitivity of the hindpaw, enhanced excitability and spontaneous activity of sensory neurons, and locally elevated levels of inflammatory mediators including cytokines. Clinically, epidural injection of steroids (glucocorticoids) is commonly used when more conservative treatments fail, but clinical trials evaluating these treatments have yielded mixed results. There are relatively few preclinical studies of steroid effects in low back pain models. One preclinical study suggests that the mineralocorticoid receptor, also present in the DRG, may have pro-inflammatory effects that oppose the activation of the glucocorticoid receptor. Although the glucocorticoid receptor is the target of anti-inflammatory steroids, many clinically used steroids activate both receptors. This could be one explanation for the limited effects of epidural steroids in some patients. Additional preclinical research is needed to address other possible reasons for limited efficacy of steroids, such as central sensitization or presence of an ongoing inflammatory stimulus in some forms of low back pain.

【 授权许可】

   
2013 Strong et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140725015056308.pdf 907KB PDF download
77KB Image download
90KB Image download
135KB Image download
61KB Image download
【 图 表 】

【 参考文献 】
  • [1]Johannes CB, Le TK, Zhou X, Johnston JA, Dworkin RH: The prevalence of chronic pain in United States adults: results of an Internet-based survey. J Pain 2010, 11:1230-1239.
  • [2]Toblin RL, Mack KA, Perveen G, Paulozzi LJ: A population-based survey of chronic pain and its treatment with prescription drugs. Pain 2011, 152:1249-1255.
  • [3]Institute of Medicine (US) Committee on Advancing Pain Research Care, and Education: Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington DC: National Academies Press; 2011.
  • [4]Finnerup NB, Sindrup SH, Jensen TS: The evidence for pharmacological treatment of neuropathic pain. Pain 2010, 150:573-581.
  • [5]Jabri RS, Hepler M, Benzon HT: Overview of Low Back Pain Disorders. In Essentials of Pain Medicine and Regional Anesthesia, edited by Benzon HT, Raja SN, Molloy RE, Liu SS, and Fishman SM. Philadelphia: Elsevier; 2005:311-330.
  • [6]Olmarker K, Rydevik B, Nordborg C: Autologous nucleus pulposus induces neurophysiologic and histologic changes in porcine cauda equina nerve roots. Spine (Phila Pa 1976) 1993, 18:1425-1432.
  • [7]Kawakami M, Tamaki T, Weinstein JN, Hashizume H, Nishi H, Meller ST: Pathomechanism of pain-related behavior produced by allografts of intervertebral disc in the rat. Spine 1996, 21:2101-2107.
  • [8]Hu SJ, Xing JL: An experimental model for chronic compression of dorsal root ganglion produced by intervertebral foramen stenosis in the rat. Pain 1998, 77:15-23.
  • [9]Song XJ, Hu SJ, Greenquist KW, Zhang J-M, LaMotte RH: Mechanical and thermal hyperalgesia and ectopic neuronal discharge after chronic compression of dorsal root ganglia. J Neurophysiol 1999, 82:3347-3358.
  • [10]Gu X, Wang S, Yang L, Sung B, Lim G, Mao J, Zeng Q, Yang CC, Mao J: A Rat model of radicular pain induced by chronic compression of lumbar dorsal root ganglion with Surgiflo. Anesthesiology 2007, 108:113-121.
  • [11]Chen RG, Kong WW, Ge DL, Luo C, Hu SJ: Bilateral mechanical and thermal hyperalgesia and tactile allodynia after chronic compression of dorsal root ganglion in mice. Neurosci Bull 2011, 27:233-240.
  • [12]Xie WR, Deng H, Li H, Bowen TL, Strong JA, Zhang J-M: Robust increase of cutaneous sensitivity, cytokine production and sympathetic sprouting in rats with localized inflammatory irritation of the spinal ganglia. Neuroscience 2006, 142:809-822.
  • [13]Xu Q, Yaksh TL: A brief comparison of the pathophysiology of inflammatory versus neuropathic pain. Curr Opin Anaesthesiol 2011, 24:400-407.
  • [14]Amaya F, Samad TA, Barrett L, Broom DC, Woolf CJ: Periganglionic inflammation elicits a distally radiating pain hypersensitivity by promoting COX-2 induction in the dorsal root ganglion. Pain 2009, 142:59-67.
  • [15]Song XJ, Gan Q, Cao JL, Wang ZB, Rupert RL: Spinal manipulation reduces pain and hyperalgesia after lumbar intervertebral foramen inflammation in the rat. J Manipulative Physiol Ther 2006, 29:5-13.
  • [16]Xie W, Strong JA, Kim D, Shahrestani S, Zhang JM: Bursting activity in myelinated sensory neurons plays a key role in pain behavior induced by localized inflammation of the rat sensory ganglion. Neuroscience 2012, 206:212-223.
  • [17]Mogil JS: Animal models of pain: progress and challenges. Nat Rev Neurosci 2009, 10:283-294.
  • [18]Devor M, Tal M: What causes low back pain? Pain 2009, 142:11-12.
  • [19]Shamji MF, Allen KD, So S, Jing L, Adams SB Jr, Schuh R, Huebner J, Kraus VB, Friedman AH, Setton LA, Richardson WJ: Gait abnormalities and inflammatory cytokines in an autologous nucleus pulposus model of radiculopathy. Spine (Phila Pa 1976) 2009, 34:648-654.
  • [20]Olmarker K, Iwabuchi M, Larsson K, Rydevik B: Walking analysis of rats subjected to experimental disc herniation. Eur Spine J 1998, 7:394-399.
  • [21]Millecamps M, Tajerian M, Naso L, Sage EH, Stone LS: Lumbar intervertebral disc degeneration associated with axial and radiating low back pain in ageing SPARC-null mice. Pain 2012, 153:1167-1179.
  • [22]Zhang J-M, Song XJ, LaMotte RH: Enhanced excitability of sensory neurons in rats with cutaneous hyperalgesia produced by chronic compression of the dorsal root ganglion. J Neurophysiol 1999, 82:3359-3366.
  • [23]Ma C, LaMotte RH: Enhanced excitability of dissociated primary sensory neurons after chronic compression of the dorsal root ganglion in the rat. Pain 2005, 113:106-112.
  • [24]Wang JG, Strong JA, Xie W, Zhang J-M: Local inflammation in rat dorsal root ganglion alters excitability and ion currents in small-diameter sensory neurons. Anesthesiology 2007, 107:322-332.
  • [25]Xie RG, Zheng DW, Xing JL, Zhang XJ, Song Y, Xie YB, Kuang F, Dong H, You SW, Xu H, Hu SJ: Blockade of persistent sodium currents contributes to the riluzole-induced inhibition of spontaneous activity and oscillations in injured DRG neurons. PLoS One 2011, 6:e18681.
  • [26]Yang RH, Wang WT, Chen JY, Xie RG, Hu SJ: Gabapentin selectively reduces persistent sodium current in injured type-A dorsal root ganglion neurons. Pain 2009, 143:48-55.
  • [27]Xie W, Strong JA, Ye L, Mao J-X, Zhang J-M: Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia. Pain 2013. http://dx.doi.org/10.1016/j.pain.2013.02.027 webcite in press
  • [28]Djouhri L, Lawson SN: Abeta-fiber nociceptive primary afferent neurons: a review of incidence and properties in relation to other afferent A-fiber neurons in mammals. Brain Res Brain Res Rev 2004, 46:131-145.
  • [29]Woodbury CJ, Kullmann FA, McIlwrath SL, Koerber HR: Identity of myelinated cutaneous sensory neurons projecting to nocireceptive laminae following nerve injury in adult mice. J Comp Neurol 2008, 508:500-509.
  • [30]Devor M: Ectopic discharge in Abeta afferents as a source of neuropathic pain. Exp Brain Res 2009, 196:115-128.
  • [31]Otoshi K, Kikuchi S, Konno S, Sekiguchi M: The reactions of glial cells and endoneurial macrophages in the dorsal root ganglion and their contribution to pain-related behavior after application of nucleus pulposus onto the nerve root in rats. Spine (Phila Pa 1976) 2010, 35:264-271.
  • [32]de Souza Grava AL, Ferrari LF, Defino HL: Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus. Eur Spine J 2012, 21:537-545.
  • [33]Huang ZJ, Hsu E, Li HC, Rosner AL, Rupert RL, Song XJ: Topical application of compound Ibuprofen suppresses pain by inhibiting sensory neuron hyperexcitability and neuroinflammation in a rat model of intervertebral foramen inflammation. J Pain 2011, 12:141-152.
  • [34]Watanabe K, Yabuki S, Sekiguchi M, Kikuchi S, Konno S: Etanercept attenuates pain-related behavior following compression of the dorsal root ganglion in the rat. Eur Spine J 2011, 20:1877-1884.
  • [35]Sasaki N, Kikuchi S, Konno S, Sekiguchi M, Watanabe K: Anti-TNF-alpha antibody reduces pain-behavioral changes induced by epidural application of nucleus pulposus in a rat model depending on the timing of administration. Spine (Phila Pa 1976) 2007, 32:413-416.
  • [36]Murata Y, Onda A, Rydevik B, Takahashi I, Takahashi K, Olmarker K: Changes in pain behavior and histologic changes caused by application of tumor necrosis factor-alpha to the dorsal root ganglion in rats. Spine (Phila Pa 1976) 2006, 31:530-535.
  • [37]Cohen SP, White RL, Kurihara C, Larkin TM, Chang A, Griffith SR, Gilligan C, Larkin R, Morlando B, Pasquina PF, Yaksh TL, Nguyen C: Epidural steroids, etanercept, or saline in subacute sciatica: a multicenter, randomized trial. Ann Intern Med 2012, 156:551-559.
  • [38]Andrade P, Visser-Vandewalle V, Hoffmann C, Steinbusch HW, Daemen MA, Hoogland G: Role of TNF-alpha during central sensitization in preclinical studies. Neurol Sci 2011, 32:757-771.
  • [39]Goupille P, Mulleman D, Paintaud G, Watier H, Valat JP: Can sciatica induced by disc herniation be treated with tumor necrosis factor alpha blockade? Arthritis Rheum 2007, 56:3887-3895.
  • [40]White FA, Sun J, Waters SM, Ma C, Ren D, Ripsch M, Steflik J, Cortright DN, Lamotte RH, Miller RJ: Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion. Proc Natl Acad Sci USA 2005, 102:14092-14097.
  • [41]Sun JH, Yang B, Donnelly DF, Ma C, LaMotte RH: MCP-1 enhances excitability of nociceptive neurons in chronically compressed dorsal root ganglia. J Neurophysiol 2006, 96:2189-2199.
  • [42]Wang JG, Strong JA, Xie W, Yang RH, Coyle DE, Wick DM, Dorsey ED, Zhang JM: The chemokine CXCL1/growth related oncogene increases sodium currents and neuronal excitability in small diameter sensory neurons. Mol Pain 2008, 4:38. BioMed Central Full Text
  • [43]Miller RJ, Jung H, Bhangoo SK, White FA: Cytokine and chemokine regulation of sensory neuron function. Handb Exp Pharmacol 2009, 194:417-449.
  • [44]Austin PJ, Moalem-Taylor G: The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immune-like glial cells and cytokines. J Neuroimmunol 2010, 229:26-50.
  • [45]Ma C, Greenquist KW, Lamotte RH: Inflammatory mediators enhance the excitability of chronically compressed dorsal root ganglion neurons. J Neurophysiol 2006, 95:2098-2107.
  • [46]Strong JA, Xie W, Coyle DE, Zhang JM: Microarray analysis of rat sensory ganglia after local inflammation implicates novel cytokines in pain. PLoS One 2012, 7:e40779.
  • [47]Chang M, Smith S, Thorpe A, Barratt MJ, Karim F: Evaluation of phenoxybenzamine in the CFA model of pain following gene expression studies and connectivity mapping. Mol Pain 2010, 6:56. BioMed Central Full Text
  • [48]Kawakami M, Matsumoto T, Hashizume H, Kuribayashi K, Tamaki T: Epidural injection of cyclooxygenase-2 inhibitor attenuates pain-related behavior following application of nucleus pulposus to the nerve root in the rat. J Orthop Res 2002, 20:376-381.
  • [49]Gu X, Wang S, Yang L, Sung B, Lim G, Mao J, Zeng Q, Chang Y, Mao J: Time-dependent effect of epidural steroid on pain behavior induced by chronic compression of dorsal root ganglion in rats. Brain Res 2007, 1174:39-46.
  • [50]Sedlak D, Paguio A, Bartunek P: Two panels of steroid receptor luciferase reporter cell lines for compound profiling. Comb Chem High Throughput Screen 2011, 14:248-266.
  • [51]Grossmann C, Scholz T, Rochel M, Bumke-Vogt C, Oelkers W, Pfeiffer AF, Diederich S, Bahr V: Transactivation via the human glucocorticoid and mineralocorticoid receptor by therapeutically used steroids in CV-1 cells: a comparison of their glucocorticoid and mineralocorticoid properties. Eur J Endocrinol 2004, 151:397-406.
  • [52]Rickard AJ, Young MJ: Corticosteroid receptors, macrophages and cardiovascular disease. J Mol Endocrinol 2009, 42:449-459.
  • [53]Dong F, Xie W, Strong JA, Zhang J-M: The mineralocorticoid receptor blocker eplerenone reduces pain behaviors in vivo and decreases excitability in small diameter sensory neurons from local inflamed dorsal root ganglia in vitro. Anesthesiology 2012, 117:1102-1112.
  • [54]Tachihara H, Sekiguchi M, Kikuchi S, Konno S: Do corticosteroids produce additional benefit in nerve root infiltration for lumbar disc herniation? Spine (Phila Pa 1976) 2008, 33:743-747.
  • [55]Gu X, Peng L, Yang D, Ma Q, Zheng Y, Liu C, Zhu B, Song L, Sun X, Ma Z: The respective and interaction effects of spinal GRs and MRs on radicular pain induced by chronic compression of the dorsal root ganglion in the rat. Brain Res 2011, 1396:88-95.
  • [56]Sun YE, Peng L, Sun X, Bo J, Yang D, Zheng Y, Liu C, Zhu B, Ma Z, Gu X: Intrathecal injection of spironolactone attenuates radicular pain by inhibition of spinal microglia activation in a rat model. PLoS One 2012, 7:e39897.
  • [57]Wang S, Lim G, Zeng Q, Sung B, Ai Y, Guo G, Yang L, Mao J: Expression of central glucocorticoid receptors after peripheral nerve injury contributes to neuropathic pain behaviors in rats. J Neurosci 2004, 24:8595-8605.
  • [58]Ma ZL, Zhang W, Gu XP, Yang WS, Zeng YM: Effects of intrathecal injection of prednisolone acetate on expression of NR2B subunit and nNOS in spinal cord of rats after chronic compression of dorsal root ganglia. Ann Clin Lab Sci 2007, 37:349-355.
  • [59]Benoist M, Boulu P, Hayem G: Epidural steroid injections in the management of low-back pain with radiculopathy: an update of their efficacy and safety. Eur Spine J 2012, 21:204-213.
  • [60]Manchikanti L, Buenaventura RM, Manchikanti KN, Ruan X, Gupta S, Smith HS, Christo PJ, Ward SP: Effectiveness of therapeutic lumbar transforaminal epidural steroid injections in managing lumbar spinal pain. Pain Physician 2012, 15:E199-245.
  • [61]Modi H, Chung KJ, Yoon HS, Yoo HS, Yoo JH: Local application of low-dose Depo-Medrol is effective in reducing immediate postoperative back pain. Int Orthop 2009, 33:737-743.
  • [62]Arden NK, Price C, Reading I, Stubbing J, Hazelgrove J, Dunne C, Michel M, Rogers P, Cooper C: A multicentre randomized controlled trial of epidural corticosteroid injections for sciatica: the WEST study. Rheumatology (Oxford) 2005, 44:1399-1406.
  • [63]Wilson-MacDonald J, Burt G, Griffin D, Glynn C: Epidural steroid injection for nerve root compression. A randomised, controlled trial. J Bone Joint Surg Br 2005, 87:352-355.
  • [64]Manchikanti L, Singh V, Cash KA, Pampati V, Datta S: Fluoroscopic caudal epidural injections in managing post lumbar surgery syndrome: two-year results of a randomized, double-blind, active-control trial. Int J Med Sci 2012, 9:582-591.
  • [65]Manchikanti L, Cash KA, McManus CD, Pampati V, Fellows B: Results of 2-year follow-up of a randomized, double-blind, controlled trial of fluoroscopic caudal epidural injections in central spinal stenosis. Pain Physician 2012, 15:371-384.
  • [66]Dirks NL, Li S, Huth B, Hochhaus G, Yates CR, Meibohm B: Transrepression and transactivation potencies of inhaled glucocorticoids. Pharmazie 2008, 63:893-898.
  • [67]Queisser N, Schupp N: Aldosterone, oxidative stress, and NF-kappaB activation in hypertension-related cardiovascular and renal diseases. Free Radic Biol Med 2012, 53:314-327.
  • [68]Woolf CJ: Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011, 152:S2-15.
  • [69]Latremoliere A, Woolf CJ: Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 2009, 10:895-926.
  • [70]McCarthy CJ, Roberts C, Gittins M, Oldham JA: A process of subgroup identification in non-specific low back pain using a standard clinical examination and cluster analysis. Physiother Res Int 2012, 17:92-100.
  • [71]Smart KM, Blake C, Staines A, Thacker M, Doody C: Mechanisms-based classifications of musculoskeletal pain: part 1 of 3: symptoms and signs of central sensitisation in patients with low back (+/− leg) pain. Man Ther 2012, 17:336-344.
  • [72]Staud R: Evidence for shared pain mechanisms in osteoarthritis, low back pain, and fibromyalgia. Curr Rheumatol Rep 2011, 13:513-520.
  • [73]O’Neill S, Manniche C, Graven-Nielsen T, Arendt-Nielsen L: Generalized deep-tissue hyperalgesia in patients with chronic low-back pain. Eur J Pain 2007, 11:415-420.
  文献评价指标  
  下载次数:21次 浏览次数:12次