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Pain vulnerability: a neurobiological perspective

Abstract

There are many known risk factors for chronic pain conditions, yet the biological underpinnings that link these factors to abnormal processing of painful signals are only just beginning to be explored. This Review will discuss the potential mechanisms that have been proposed to underlie vulnerability and resilience toward developing chronic pain. Particular focus will be given to genetic and epigenetic processes, priming effects on a cellular level, and alterations in brain networks concerned with reward, motivation/learning and descending modulatory control. Although research in this area is still in its infancy, a better understanding of how pain vulnerability emerges has the potential to help identify individuals at risk and may open up new therapeutic avenues.

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Figure 1: Various risk factors have been identified for chronic pain, such as genetic, environmental and personality factors.
Figure 2: Polymorphisms in the DNA sequence and epigenetic mechanisms such as DNA methylation and histone modifications determine some risk from birth that can lead to transcriptome and connectivity differences.
Figure 3: Adverse events, such as stress, injury or disease, can challenge and modify the hardwired system at different levels, including epigenetic, cell biological, and systems and network levels.
Figure 4: Various brain networks may be involved in conferring vulnerability to painful conditions, particularly the reward-motivation network (purple regions) and the DPMS (green regions).

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References

  1. Kehlet, H., Jensen, T.S. & Woolf, C.J. Persistent postsurgical pain: risk factors and prevention. Lancet 367, 1618–1625 (2006).

    PubMed  Google Scholar 

  2. Dieppe, P.A. & Lohmander, L.S. Pathogenesis and management of pain in osteoarthritis. Lancet 365, 965–973 (2005).

    CAS  PubMed  Google Scholar 

  3. Balagué, F., Mannion, A.F., Pellise, F. & Cedraschi, C. Non-specific low back pain. Lancet 379, 482–491 (2012).

    PubMed  Google Scholar 

  4. Abbott, C.A., Malik, R.A., van Ross, E.R., Kulkarni, J. & Boulton, A.J. Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K. Diabetes Care 34, 2220–2224 (2011).

    PubMed  PubMed Central  Google Scholar 

  5. Crow, M., Denk, F. & McMahon, S.B. Genes and epigenetic processes as prospective pain targets. Genome Med. 5, 12 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Mogil, J.S. Pain genetics: past, present and future. Trends Genet. 28, 258–266 (2012).

    CAS  PubMed  Google Scholar 

  7. Cox, J.J. & Wood, J.N. No pain, more gain. Nat. Genet. 45, 1271–1272 (2013).

    CAS  PubMed  Google Scholar 

  8. McMahon, S.B. NGF as a mediator of inflammatory pain. Phil. Trans. R. Soc. Lond. B 351, 431–440 (1996).

    CAS  Google Scholar 

  9. Eijkelkamp, N. et al. Neurological perspectives on voltage-gated sodium channels. Brain 135, 2585–2612 (2012).

    PubMed  PubMed Central  Google Scholar 

  10. Hocking, L.J., Morris, A.D., Dominiczak, A.F., Porteous, D.J. & Smith, B.H. Heritability of chronic pain in 2195 extended families. Eur. J. Pain 16, 1053–1063 (2012).

    CAS  PubMed  Google Scholar 

  11. Malfait, A.M. et al. A role for PACE4 in osteoarthritis pain: evidence from human genetic association and null mutant phenotype. Ann. Rheum. Dis. 71, 1042–1048 (2012).

    CAS  PubMed  Google Scholar 

  12. Tsantoulas, C. et al. Sensory neuron downregulation of the Kv9.1 potassium channel subunit mediates neuropathic pain following nerve injury. J. Neurosci. 32, 17502–17513 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. arcOgen Consortium. Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study. Lancet 380, 815–823 (2012).

  14. Williams, F.M. et al. Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects. Ann. Rheum. Dis. 72, 1141–1148 (2013).

    CAS  PubMed  Google Scholar 

  15. Nyholt, D.R. et al. Genome-wide association meta-analysis identifies new endometriosis risk loci. Nat. Genet. 44, 1355–1359 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Esserlind, A.L. et al. Replication and meta-analysis of common variants identifies a genome-wide significant locus in migraine. Eur. J. Neurol. 20, 765–772 (2013).

    PubMed  Google Scholar 

  17. Kim, H., Ramsay, E., Lee, H., Wahl, S. & Dionne, R.A. Genome-wide association study of acute post-surgical pain in humans. Pharmacogenomics 10, 171–179 (2009).

    CAS  PubMed  Google Scholar 

  18. Nishizawa, D. et al. Genome-wide association study identifies a potent locus associated with human opioid sensitivity. Mol. Psychiatry published online, doi:10.1038/mp.2012.164 (27 November 2012).

    PubMed  PubMed Central  Google Scholar 

  19. Peters, M.J. et al. Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region. Ann. Rheum. Dis. 72, 427–436 (2013).

    CAS  PubMed  Google Scholar 

  20. Williams, F.M. et al. Genes contributing to pain sensitivity in the normal population: an exome sequencing study. PLoS Genet. 8, e1003095 (2012).

    PubMed  PubMed Central  Google Scholar 

  21. Chesler, E.J., Wilson, S.G., Lariviere, W.R., Rodriguez-Zas, S.L. & Mogil, J.S. Influences of laboratory environment on behavior. Nat. Neurosci. 5, 1101–1102 (2002).

    CAS  PubMed  Google Scholar 

  22. Fillingim, R.B. et al. The A118G single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans. J. Pain 6, 159–167 (2005).

    CAS  PubMed  Google Scholar 

  23. Sorge, R.E. et al. Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity. Nat. Med. 18, 595–599 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Lee, M. & Tracey, I. Neuro-genetics of persistent pain. Curr. Opin. Neurobiol. 23, 127–132 (2013).

    CAS  PubMed  Google Scholar 

  25. Bishop, S. & Forster, S. Trait anxiety, neuroticism and the brain basis of vulnerability to affective disorder. in The Cambridge Handbook of Human Affective Neuroscience (eds. Armony, J. & Vuilleumier, P.) ch. 24 (Cambridge University Press, Cambridge, 2013).

  26. Dulac, C. Brain function and chromatin plasticity. Nature 465, 728–735 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Tajerian, M. et al. DNA methylation of SPARC and chronic low back pain. Mol. Pain 7, 65 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Wu, H. & Zhang, Y. Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation. Genes Dev. 25, 2436–2452 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Telese, F., Gamliel, A., Skowronska-Krawczyk, D., Garcia-Bassets, I. & Rosenfeld, M.G. “Seq-ing” insights into the epigenetics of neuronal gene regulation. Neuron 77, 606–623 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Buchen, L. Neuroscience: In their nurture. Nature 467, 146–148 (2010).

    CAS  PubMed  Google Scholar 

  31. Bell, J.T. et al. Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet. 8, e1002629 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Denk, F. & McMahon, S.B. Chronic pain: emerging evidence for the involvement of epigenetics. Neuron 73, 435–444 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Denk, F. et al. HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain. Pain 154, 1668–1679 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Henikoff, S. & Shilatifard, A. Histone modification: cause or cog? Trends Genet. 27, 389–396 (2011).

    CAS  PubMed  Google Scholar 

  35. Wang, Y. et al. Intrathecal 5-azacytidine inhibits global DNA methylation and methyl-CpG–binding protein 2 expression and alleviates neuropathic pain in rats following chronic constriction injury. Brain Res. 1418, 64–69 (2011).

    CAS  PubMed  Google Scholar 

  36. Stresemann, C., Brueckner, B., Musch, T., Stopper, H. & Lyko, F. Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines. Cancer Res. 66, 2794–2800 (2006).

    CAS  PubMed  Google Scholar 

  37. Tajerian, M. et al. Peripheral nerve injury is associated with chronic, reversible changes in global DNA methylation in the mouse prefrontal cortex. PLoS ONE 8, e55259 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Doehring, A., Oertel, B.G., Sittl, R. & Lotsch, J. Chronic opioid use is associated with increased DNA methylation correlating with increased clinical pain. Pain 154, 15–23 (2013).

    CAS  PubMed  Google Scholar 

  39. Tochiki, K.K., Cunningham, J., Hunt, S.P. & Geranton, S.M. The expression of spinal methyl-CpG–binding protein 2, DNA methyltransferases and histone deacetylases is modulated in persistent pain states. Mol. Pain 8, 14 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Downs, J. et al. Linking MECP2 and pain sensitivity: the example of Rett syndrome. Am. J. Med. Genet. A. 152A, 1197–1205 (2010).

    PubMed  Google Scholar 

  41. Skene, P.J. et al. Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state. Mol. Cell 37, 457–468 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Graur, D. et al. On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE. Genome Biol. Evol. 5, 578–590 (2013).

    PubMed  PubMed Central  Google Scholar 

  43. Low, L.A. & Fitzgerald, M. Acute pain and a motivational pathway in adult rats: influence of early life pain experience. PLoS ONE 7, e34316 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Coutinho, S.V. et al. Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. Am. J. Physiol. Gastrointest. Liver Physiol. 282, G307–G316 (2002).

    CAS  PubMed  Google Scholar 

  45. Moloney, R.D. et al. Early-life stress induces visceral hypersensitivity in mice. Neurosci. Lett. 512, 99–102 (2012).

    CAS  PubMed  Google Scholar 

  46. Beggs, S., Currie, G., Salter, M.W., Fitzgerald, M. & Walker, S.M. Priming of adult pain responses by neonatal pain experience: maintenance by central neuroimmune activity. Brain 135, 404–417 (2012).

    PubMed  Google Scholar 

  47. Doesburg, S.M. et al. Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age. Pain 154, 1946–1952 (2013).

    PubMed  PubMed Central  Google Scholar 

  48. Hohmeister, J. et al. Cerebral processing of pain in school-aged children with neonatal nociceptive input: an exploratory fMRI study. Pain 150, 257–267 (2010).

    PubMed  Google Scholar 

  49. Reichling, D.B. & Levine, J.D. Critical role of nociceptor plasticity in chronic pain. Trends Neurosci. 32, 611–618 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Loram, L.C. et al. Prior exposure to glucocorticoids potentiates lipopolysaccharide induced mechanical allodynia and spinal neuroinflammation. Brain Behav. Immun. 25, 1408–1415 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Bogen, O., Alessandri-Haber, N., Chu, C., Gear, R.W. & Levine, J.D. Generation of a pain memory in the primary afferent nociceptor triggered by PKCepsilon activation of CPEB. J. Neurosci. 32, 2018–2026 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Johansen-Berg, H. Behavioural relevance of variation in white matter microstructure. Curr. Opin. Neurol. 23, 351–358 (2010).

    PubMed  Google Scholar 

  53. Filippini, N. et al. Differential effects of the APOE genotype on brain function across the lifespan. Neuroimage 54, 602–610 (2011).

    CAS  PubMed  Google Scholar 

  54. Tracey, I. et al. Imaging attentional modulation of pain in the periaqueductal gray in humans. J. Neurosci. 22, 2748–2752 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Ploner, M., Lee, M.C., Wiech, K., Bingel, U. & Tracey, I. Prestimulus functional connectivity determines pain perception in humans. Proc. Natl. Acad. Sci. USA 107, 355–360 (2010).

    CAS  PubMed  Google Scholar 

  56. Coghill, R.C., McHaffie, J.G. & Yen, Y.F. Neural correlates of interindividual differences in the subjective experience of pain. Proc. Natl. Acad. Sci. USA 100, 8538–8542 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Erpelding, N., Moayedi, M. & Davis, K.D. Cortical thickness correlates of pain and temperature sensitivity. Pain 153, 1602–1609 (2012).

    PubMed  Google Scholar 

  58. Foerster, B.R. et al. Reduced insular gamma-aminobutyric acid in fibromyalgia. Arthritis Rheum. 64, 579–583 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Gwilym, S.E. et al. Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients. Arthritis Rheum. 61, 1226–1234 (2009).

    PubMed  Google Scholar 

  60. Wanigasekera, V. et al. Baseline reward circuitry activity and trait reward responsiveness predict expression of opioid analgesia in healthy subjects. Proc. Natl. Acad. Sci. USA 109, 17705–17710 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Baliki, M.N. et al. Corticostriatal functional connectivity predicts transition to chronic back pain. Nat. Neurosci. 15, 1117–1119 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Mansour, A.R. et al. Brain white matter structural properties predict transition to chronic pain. Pain 154, 2160–2168 (2013).

    PubMed  PubMed Central  Google Scholar 

  63. Baliki, M.N., Geha, P.Y., Fields, H.L. & Apkarian, A.V. Predicting value of pain and analgesia: nucleus accumbens response to noxious stimuli changes in the presence of chronic pain. Neuron 66, 149–160 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Becerra, L., Breiter, H.C., Wise, R., Gonzalez, R.G. & Borsook, D. Reward circuitry activation by noxious thermal stimuli. Neuron 32, 927–946 (2001).

    CAS  PubMed  Google Scholar 

  65. Wood, P.B. et al. Fibromyalgia patients show an abnormal dopamine response to pain. Eur. J. Neurosci. 25, 3576–3582 (2007).

    PubMed  Google Scholar 

  66. Schweinhardt, P., Seminowicz, D.A., Jaeger, E., Duncan, G.H. & Bushnell, M.C. The anatomy of the mesolimbic reward system: a link between personality and the placebo analgesic response. J. Neurosci. 29, 4882–4887 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Leknes, S. et al. The importance of context: when relative relief renders pain pleasant. Pain 154, 402–410 (2013).

    PubMed  PubMed Central  Google Scholar 

  68. Tracey, I. & Dickenson, A. SnapShot: pain perception. Cell 148, 1308–1308.e2 (2012).

    CAS  PubMed  Google Scholar 

  69. Heinricher, M.M., Tavares, I., Leith, J.L. & Lumb, B.M. Descending control of nociception: Specificity, recruitment and plasticity. Brain Res. Rev. 60, 214–225 (2009).

    CAS  PubMed  Google Scholar 

  70. Lee, M.C., Zambreanu, L., Menon, D.K. & Tracey, I. Identifying brain activity specifically related to the maintenance and perceptual consequence of central sensitization in humans. J. Neurosci. 28, 11642–11649 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Eippert, F., Finsterbusch, J., Bingel, U. & Buchel, C. Direct evidence for spinal cord involvement in placebo analgesia. Science 326, 404 (2009).

    CAS  PubMed  Google Scholar 

  72. Geuter, S. & Buchel, C. Facilitation of pain in the human spinal cord by nocebo treatment. J. Neurosci. 33, 13784–13790 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Weissman-Fogel, I. et al. Enhanced presurgical pain temporal summation response predicts post-thoracotomy pain intensity during the acute postoperative phase. J. Pain 10, 628–636 (2009).

    PubMed  Google Scholar 

  74. Yarnitsky, D. Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Curr. Opin. Anaesthesiol. 23, 611–615 (2010).

    PubMed  Google Scholar 

  75. Yarnitsky, D. et al. Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk. Pain 138, 22–28 (2008).

    PubMed  Google Scholar 

  76. Yarnitsky, D., Granot, M., Nahman-Averbuch, H., Khamaisi, M. & Granovsky, Y. Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy. Pain 153, 1193–1198 (2012).

    CAS  PubMed  Google Scholar 

  77. De Felice, M. et al. Engagement of descending inhibition from the rostral ventromedial medulla protects against chronic neuropathic pain. Pain 152, 2701–2709 (2011).

    PubMed  PubMed Central  Google Scholar 

  78. Wang, R. et al. Descending facilitation maintains long-term spontaneous neuropathic pain. J. Pain 14, 845–853 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Hathway, G.J., Koch, S., Low, L. & Fitzgerald, M. The changing balance of brainstem-spinal cord modulation of pain processing over the first weeks of rat postnatal life. J. Physiol. (Lond.) 587, 2927–2935 (2009).

    CAS  Google Scholar 

  80. Hathway, G.J., Vega-Avelaira, D. & Fitzgerald, M. A critical period in the supraspinal control of pain: opioid-dependent changes in brainstem rostroventral medulla function in preadolescence. Pain 153, 775–783 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Vega-Avelaira, D., McKelvey, R., Hathway, G. & Fitzgerald, M. The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury. Mol. Pain 8, 30 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Smith, Y.R. et al. Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. J. Neurosci. 26, 5777–5785 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Vincent, K. et al. Brain imaging reveals that engagement of descending inhibitory pain pathways in healthy women in a low endogenous estradiol state varies with testosterone. Pain 154, 515–524 (2013).

    CAS  PubMed  Google Scholar 

  84. Tu, C.H. et al. Menstrual pain is associated with rapid structural alterations in the brain. Pain 154, 1718–1724 (2013).

    PubMed  Google Scholar 

  85. Vincent, K. et al. Dysmenorrhoea is associated with central changes in otherwise healthy women. Pain 152, 1966–1975 (2011).

    PubMed  Google Scholar 

  86. Labus, J.S. et al. Sex differences in emotion-related cognitive processes in irritable bowel syndrome and healthy control subjects. Pain 154, 2088–2099 (2013).

    PubMed  PubMed Central  Google Scholar 

  87. Moayedi, M. et al. Contribution of chronic pain and neuroticism to abnormal forebrain gray matter in patients with temporomandibular disorder. Neuroimage 55, 277–286 (2011).

    PubMed  Google Scholar 

  88. Chen, J.Y., Blankstein, U., Diamant, N.E. & Davis, K.D. White matter abnormalities in irritable bowel syndrome and relation to individual factors. Brain Res. 1392, 121–131 (2011).

    CAS  PubMed  Google Scholar 

  89. Erpelding, N. & Davis, K.D. Neural underpinnings of behavioural strategies that prioritize either cognitive task performance or pain. Pain 154, 2060–2071 (2013).

    PubMed  Google Scholar 

  90. Kuchinad, A. et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain? J. Neurosci. 27, 4004–4007 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Villemure, C., Ceko, M., Cotton, V.A. & Bushnell, M.C. Insular cortex mediates increased pain tolerance in yoga practitioners. Cereb. Cortex published online, 10.1093/cercor/bht123 (21 May 2013).

  92. Coggon, D.I. & Martyn, C.N. Time and chance: the stochastic nature of disease causation. Lancet 365, 1434–1437 (2005).

    CAS  PubMed  Google Scholar 

  93. Hashmi, J.A. et al. Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits. Brain 136, 2751–2768 (2013).

    PubMed  PubMed Central  Google Scholar 

  94. Segerdahl, A.R. et al. Imaging the neural correlates of neuropathic pain and pleasurable relief associated with inherited erythromelalgia in a single subject with quantitative arterial spin labelling. Pain 153, 1122–1127 (2012).

    PubMed  PubMed Central  Google Scholar 

  95. Ploghaus, A. et al. Dissociating pain from its anticipation in the human brain. Science 284, 1979–1981 (1999).

    CAS  PubMed  Google Scholar 

  96. Bushnell, M.C., Ceko, M. & Low, L.A. Cognitive and emotional control of pain and its disruption in chronic pain. Nat. Rev. Neurosci. 14, 502–511 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Mouraux, A., Diukova, A., Lee, M.C., Wise, R.G. & Iannetti, G.D. A multisensory investigation of the functional significance of the “pain matrix”. Neuroimage 54, 2237–2249 (2011).

    PubMed  Google Scholar 

  98. Garcia-Larrea, L. & Peyron, R. Pain matrices and neuropathic pain matrices: a review. Pain (in the press).

  99. Wager, T.D. et al. An fMRI-based neurologic signature of physical pain. N. Engl. J. Med. 368, 1388–1397 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Covington, H.E. III et al. A role for repressive histone methylation in cocaine-induced vulnerability to stress. Neuron 71, 656–670 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

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The authors are supported by grants from the Wellcome Trust.

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Denk, F., McMahon, S. & Tracey, I. Pain vulnerability: a neurobiological perspective. Nat Neurosci 17, 192–200 (2014). https://doi.org/10.1038/nn.3628

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