An epigenetic hypothesis for the genomic memory of pain

Frontiers in Cellular Neuroscience

Volumn 9, Issue , 2015, Pages

  Alvarado, Sebastian ^a,b   Tajerian, Maral ^a,b,c   Suderman, Matthew ^b   Machnes, Ziv ^b   Pierfelice, Stephanie ^b   Millecamps, Magali ^b,c   Stone, Laura S ^b,c   Szyf, Moshe ^b  

^a STANFORD UNIVERSITY   (United States)

^b MCGILL UNIVERSITY   (Canada)

^c MCGILL UNIVERSITY   (Canada)

Author keywords

Chronic pain; DNA methylation; Epigenetics; Neuropathy; Neuroplasticity; Prefrontal cortex; Synaptotagmin

Indexed keywords

DNA METHYLTRANSFERASE; EARLY GROWTH RESPONSE FACTOR 1; SYNAPTOTAGMIN II; UNTRANSLATED RNA;

ARTICLE; CHRONIC PAIN; DNA METHYLATION; EPIGENETICS; GENE EXPRESSION; GENETIC POLYMORPHISM; HUMAN; LOW BACK PAIN; MEMORY; NERVE CELL PLASTICITY; NEUROPATHIC PAIN; PERIPHERAL NERVE INJURY; PREFRONTAL CORTEX;

EID: 84939628684     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2015.00088     Document Type: Article

References (110)

1. Alvarado, S., Tajerian, M., Millecamps, M., Suderman, M., Stone, L. S., and Szyf, M. (2013). Peripheral nerve injury is accompanied by chronic transcriptome-wide changes in the mouse prefrontal cortex. Mol. Pain 9:21. doi: 10.1186/1744-8069-9-21
2. Apkarian, A. V., Baliki, M. N., and Geha, P. Y. (2009). Towards a theory of chronic pain. Prog. Neurobiol. 87, 81-97. doi: 10.1016/j.pneurobio.2008.09.018
3. Apkarian, A. V., Bushnell, M. C., Treede, R. D., and Zubieta, J. K. (2005). Human brain mechanisms of pain perception and regulation in health and disease. Eur. J. Pain 9, 463-484. doi: 10.1016/j.ejpain.2004.11.001
4. Apkarian, A. V., Sosa, Y., Krauss, B. R., Thomas, P. S., Fredrickson, B. E., Levy, R. E., et al. (2004). Chronic pain patients are impaired on an emotional decision-making task. Pain 108, 129-136. doi: 10.1016/j.pain.2003.12.015
5. Baubec, T., Ivanek, R., Lienert, F., and Schubeler, D. (2013). Methylation-dependent and -independent genomic targeting principles of the MBD protein family. Cell 153, 480-492. doi: 10.1016/j.cell.2013.03.011
6. Berger, S. E., Baria, A. T., Baliki, M. N., Mansour, A., Herrmann, K. M., Torbey, S., et al. (2014). Risky monetary behavior in chronic back pain is associated with altered modular connectivity of the nucleus accumbens. BMC Res. Notes 7:739. doi: 10.1186/1756-0500-7-739
7. Bird, A. P. (1986). CpG-rich islands and the function of DNA methylation. Nature 321, 209-213. doi: 10.1038/321209a0
8. Brinkman, A. B., Gu, H., Bartels, S. J., Zhang, Y., Matarese, F., Simmer, F., et al. (2012). Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk. Genome Res. 22, 1128-1138. doi: 10.1101/gr.133728.111
9. Cardoso-Cruz, H., Lima, D., and Galhardo, V. (2013a). Impaired spatial memory performance in a rat model of neuropathic pain is associated with reduced hippocampus-prefrontal cortex connectivity. J. Neurosci. 33, 2465-2480. doi: 10.1523/JNEUROSCI.5197-12.2013
10. Cardoso-Cruz, H., Sousa, M., Vieira, J. B., Lima, D., and Galhardo, V. (2013b). Prefrontal cortex and mediodorsal thalamus reduced connectivity is associated with spatial working memory impairment in rats with inflammatory pain. Pain 154, 2397-2406. doi: 10.1016/j.pain.2013.07.020
11. Centeno, M. V., Mutso, A., Millecamps, M., and Apkarian, A. V. (2009). Prefrontal cortex and spinal cord mediated anti-neuropathy and analgesia induced by sarcosine, a glycine-T1 transporter inhibitor. Pain 145, 176-183. doi: 10.1016/j.pain.2009.06.014
12. Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T., Qin, J., et al. (2008). MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320, 1224-1229. doi: 10.1126/science.1153252
13. Colantuoni, C., Lipska, B. K., Ye, T., Hyde, T. M., Tao, R., Leek, J. T., et al. (2011). Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature 478, 519-523. doi: 10.1038/nature10524
14. Comb, M., and Goodman, H. M. (1990). CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2. Nucleic Acids Res. 18, 3975-3982. doi: 10.1093/nar/18.13.3975
15. Cremer, T., and Cremer, M. (2010). Chromosome territories. Cold Spring Harb. Perspect. Biol. 2:a003889. doi: 10.1101/cshperspect.a003889
16. D'Alessio, A. C., Weaver, I. C., and Szyf, M. (2007). Acetylation-induced transcription is required for active DNA demethylation in methylation-silenced genes. Mol. Cell. Biol. 27, 7462-7474. doi: 10.1128/mcb.01120-07
17. Davis, K. D., Pope, G., Chen, J., Kwan, C. L., Crawley, A. P., and Diamant, N. E. (2008). Cortical thinning in IBS: implications for homeostatic, attention and pain processing. Neurology 70, 153-154. doi: 10.1212/01.wnl.0000295509.30630.10
18. Day, J. J., Childs, D., Guzman-Karlsson, M. C., Kibe, M., Moulden, J., Song, E., et al. (2013). DNA methylation regulates associative reward learning. Nat. Neurosci. 16, 1445-1452. doi: 10.1038/nn.3504
19. Day, J. J., and Sweatt, J. D. (2010). DNA methylation and memory formation. Nat. Neurosci. 13, 1319-1323. doi: 10.1038/nn.2666
20. De Jager, P. L., Srivastava, G., Lunnon, K., Burgess, J., Schalkwyk, L. C., Yu, L., et al. (2014). Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nat. Neurosci. 17, 1156-1163. doi: 10.1038/nn.3786
21. Dias, B. G., and Ressler, K. J. (2014). Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat. Neurosci. 17, 89-96. doi: 10.1038/nn.3594
22. Di Ruscio, A., Ebralidze, A. K., Benoukraf, T., Amabile, G., Goff, L. A., Terragni, J., et al. (2013). DNMT1-interacting RNAs block gene specific DNA methylation. Nature 503, 371-376. doi: 10.1038/nature12598
23. Eden, A., Gaudet, F., Waghmare, A., and Jaenisch, R. (2003). Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300:455. doi: 10.1126/science.1083557
24. ENCODE Project Consortium (2011). A user's guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol. 9:e1001046. doi: 10.1371/journal.pbio.1001046
25. Feng, J., Zhou, Y., Campbell, S. L., Le, T., Li, E., Sweatt, J. D., et al. (2010). Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat. Neurosci. 13, 423-430. doi: 10.1038/nn.2514
26. Flanagan, J. M., and Wild, L. (2007). An epigenetic role for noncoding RNAs and intragenic DNA methylation. Genome Biol. 8:307. doi: 10.1186/gb-2007-8-6-307
27. Foret, S., Kucharski, R., Pellegrini, M., Feng, S., Jacobsen, S. E., Robinson, G. E., et al. (2012). DNA methylation dynamics, metabolic fluxes, gene splicing and alternative phenotypes in honey bees. Proc. Natl. Acad. Sci. U S A 109, 4968-4973. doi: 10.1073/pnas.1202392109
28. Freeman, S. H., Kandel, R., Cruz, L., Rozkalne, A., Newell, K., Frosch, M. P., et al. (2008). Preservation of neuronal number despite age-related cortical brain atrophy in elderly subjects without Alzheimer disease. J. Neuropathol. Exp. Neurol. 67, 1205-1212. doi: 10.1097/NEN.0b013e31818fc72f
29. Fuso, A., Nicolia, V., Cavallaro, R. A., and Scarpa, S. (2011). DNA methylase and demethylase activities are modulated by one-carbon metabolism in Alzheimer's disease models. J. Nutr. Biochem. 22, 242-251. doi: 10.1016/j.jnutbio.2010.01.010
30. Giesecke, T., Gracely, R. H., Grant, M. A., Nachemson, A., Petzke, F., Williams, D. A., et al. (2004). Evidence of augmented central pain processing in idiopathic chronic low back pain. Arthritis Rheum. 50, 613-623. doi: 10.1002/art.20063
31. Guo, J. U., Su, Y., Shin, J. H., Shin, J., Li, H., Xie, B., et al. (2013). Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat. Neurosci. 17, 215-222. doi: 10.1038/nn.3607
32. Hahnen, E., Eyüpoglu, I. Y., Brichta, L., Haastert, K., Tränkle, C., Siebzehnrübl, F. A., et al. (2006). In vitro and ex vivo evaluation of second-generation histone deacetylase inhibitors for the treatment of spinal muscular atrophy. J. Neurochem. 98, 193-202. doi: 10.1111/j.1471-4159.2006.03868.x
33. Han, L., Su, B., Li, W.-H., and Zhao, Z. (2008). CpG island density and its correlations with genomic features in mammalian genomes. Genome Biol. 9:R79. doi: 10.1186/gb-2008-9-5-r79
34. Hon, G. C., Rajagopal, N., Shen, Y., McCleary, D. F., Yue, F., Dang, M. D., et al. (2013). Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues. Nat. Genet. 45, 1198-1206. doi: 10.1038/ng.2746
35. Hötting, K., and Röder, B. (2013). Beneficial effects of physical exercise on neuroplasticity and cognition. Neurosci. Biobehav. Rev. 37, 2243-2257. doi: 10.1016/j.neubiorev.2013.04.005
36. Hsu, P. D., Lander, E. S., and Zhang, F. (2014). Development and applications of CRISPR-Cas9 for genome engineering. Cell 157, 1262-1278. doi: 10.1016/j.cell.2014.05.010
37. Humphries, C., and Kohli, M. A. (2014). Rare variants and transcriptomics in Alzheimer disease. Curr. Genet. Med. Rep. 2, 75-84. doi: 10.1007/s40142-014-0035-9
38. Imai, S., Saeki, M., Yanase, M., Horiuchi, H., Abe, M., Narita, M., et al. (2011). Change in microRNAs associated with neuronal adaptive responses in the nucleus accumbens under neuropathic pain. J. Neurosci. 31, 15294-15299. doi: 10.1523/JNEUROSCI.0921-11.2011
39. Iskandar, B. J., Rizk, E., Meier, B., Hariharan, N., Bottiglieri, T., Finnell, R. H., et al. (2010). Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation. J. Clin. Invest. 120, 1603-1616. doi: 10.1172/JCI40000
40. Ito, S., D'Alessio, A. C., Taranova, O. V., Hong, K., Sowers, L. C., and Zhang, Y. (2010). Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466, 1129-1133. doi: 10.1038/nature09303
41. Iwamoto, K., Bundo, M., Ueda, J., Oldham, M. C., Ukai, W., Hashimoto, E., et al. (2011). Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons. Genome Res. 21, 688-696. doi: 10.1101/gr.112755.110
42. Jimenez-Useche, I., Ke, J., Tian, Y., Shim, D., Howell, S. C., Qiu, X., et al. (2013). DNA methylation regulated nucleosome dynamics. Sci. Rep. 3:2121. doi: 10.1038/srep02121
43. Khan, S. A., Keaser, M. L., Meiller, T. F., and Seminowicz, D. A. (2014). Altered structure and function in the hippocampus and medial prefrontal cortex in patients with burning mouth syndrome. Pain 155, 1472-1480. doi: 10.1016/j.pain.2014.04.022
44. Kochubey, O., and Schneggenburger, R. (2011). Synaptotagmin increases the dynamic range of synapses by driving Ca2+-evoked release and by clamping a near-linear remaining Ca2+ sensor. Neuron 69, 736-748. doi: 10.1016/j.neuron.2011.01.013
45. Kraft, P., and Hunter, D. J. (2009). Genetic risk prediction-are we there yet? N. Engl. J. Med. 360, 1701-1703. doi: 10.1056/NEJMp0810107
46. Krause, T., Asseyer, S., Taskin, B., Flöel, A., Witte, A. V., Mueller, K., et al. (2014). The cortical signature of central poststroke pain: gray matter decreases in somatosensory, insular and prefrontal cortices. Cereb. Cortex doi: 10.1093/cercor/bhu177. [Epub ahead of print].
47. Kriaucionis, S., and Heintz, N. (2009). The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324, 929-930. doi: 10.1126/science.1169786
48. Kuchinad, A., Schweinhardt, P., Seminowicz, D. A., Wood, P. B., Chizh, B. A., and Bushnell, M. C. (2007). Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain? J. Neurosci. 27, 4004-4007. doi: 10.1523/jneurosci.0098-07.2007
49. Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., et al. (2001). Initial sequencing and analysis of the human genome. Nature 409, 860-921. doi: 10.1038/35057062
50. Lenhard, B., Sandelin, A., and Carninci, P. (2012). Metazoan promoters: emerging characteristics and insights into transcriptional regulation. Nat. Rev. Genet. 13, 233-245. doi: 10.1038/nrg3163
51. Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., et al. (2013). Global epigenomic reconfiguration during mammalian brain development. Science 341:1237905. doi: 10.1126/science.1237905
52. Lister, R., Pelizzola, M., Dowen, R. H., Hawkins, R. D., Hon, G., Tonti-Filippini, J., et al. (2009). Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462, 315-322. doi: 10.1038/nature08514
53. Low, L. A. (2013). The impact of pain upon cognition: what have rodent studies told us? Pain 154, 2603-2605. doi: 10.1016/j.pain.2013.06.012
54. Lubin, F. D., Roth, T. L., and Sweatt, J. D. (2008). Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J. Neurosci. 28, 10576-10586. doi: 10.1523/JNEUROSCI.1786-08.2008
55. Machnes, Z. M., Huang, T. C., Chang, P. K., Gill, R., Reist, N., Dezsi, G., et al. (2013). DNA methylation mediates persistent epileptiform activity in vitro and in vivo. PLoS One 8:e76299. doi: 10.1371/journal.pone.0076299
56. Maeder, M. L., Angstman, J. F., Richardson, M. E., Linder, S. J., Cascio, V. M., Tsai, S. Q., et al. (2013). Targeted DNA Demethylation and endogenous gene activation using programmable TALE-TET1 fusions. Nat. Biotechnol. 31, 1137-1142. doi: 10.1038/nbt.2726
57. Maret, S., Dorsaz, S., Gurcel, L., Pradervand, S., Petit, B., Pfister, C., et al. (2007). Homer1a is a core brain molecular correlate of sleep loss. Proc. Natl. Acad. Sci. U S A 104, 20090-20095. doi: 10.1073/pnas.0710131104
58. Masliah, E., and Terry, R. (1993). The role of synaptic proteins in the pathogenesis of disorders of the central nervous system. Brain Pathol. 3, 77-85. doi: 10.1111/j.1750-3639.1993.tb00728.x
59. Massart, R., Freyburger, M., Suderman, M., Paquet, J., El Helou, J., Belanger-Nelson, E., et al. (2014a). The genome-wide landscape of DNA methylation and hydroxymethylation in response to sleep deprivation impacts on synaptic plasticity genes. Transl. Psychiatry 4:e347. doi: 10.1038/tp.2013.120
60. Massart, R., Suderman, M., Provencal, N., Yi, C., Bennett, A. J., Suomi, S., et al. (2014b). Hydroxymethylation and DNA methylation profiles in the prefrontal cortex of the non-human primate rhesus macaque and the impact of maternal deprivation on hydroxymethylation. Neuroscience 268, 139-148. doi: 10.1016/j.neuroscience.2014.03.021
61. McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., et al. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat. Neurosci. 12, 342-348. doi: 10.1038/nn.2270
62. Mercer, T. R., Dinger, M. E., and Mattick, J. S. (2009). Long non-coding RNAs: insights into functions. Nat. Rev. Genet. 10, 155-159. doi: 10.1038/nrg2521
63. Mercer, T. R., Dinger, M. E., Sunkin, S. M., Mehler, M. F., and Mattick, J. S. (2008). Specific expression of long noncoding RNAs in the mouse brain. Proc. Natl. Acad. Sci. U S A 105, 716-721. doi: 10.1073/pnas.0706729105
64. Metz, A. E., Yau, H. J., Centeno, M. V., Apkarian, A. V., and Martina, M. (2009). Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain. Proc. Natl. Acad. Sci. U S A 106, 2423-2428. doi: 10.1073/pnas.0809897106
65. Miller, C. A., Campbell, S. L., and Sweatt, J. D. (2008). DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity. Neurobiol. Learn. Mem. 89, 599-603. doi: 10.1016/j.nlm.2007.07.016
66. Miller, C. A., Gavin, C. F., White, J. A., Parrish, R. R., Honasoge, A., Yancey, C. R., et al. (2010). Cortical DNA methylation maintains remote memory. Nat. Neurosci. 13, 664-666. doi: 10.1038/nn.2560
67. Miller, C. A., and Sweatt, J. D. (2007). Covalent modification of DNA regulates memory formation. Neuron 53, 857-869. doi: 10.1016/j.neuron.2007.02.022
68. Mutso, A. A., Radzicki, D., Baliki, M. N., Huang, L., Banisadr, G., Centeno, M. V., et al. (2012). Abnormalities in hippocampal functioning with persistent pain. J. Neurosci. 32, 5747-5756. doi: 10.1523/JNEUROSCI.0587-12.2012
69. Nan, X., Ng, H. H., Johnson, C. A., Laherty, C. D., Turner, B. M., Eisenman, R. N., et al. (1998). Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393, 386-389. doi: 10.1038/30764
70. Neugebauer, V., Galhardo, V., Maione, S., and Mackey, S. C. (2009). Forebrain pain mechanisms. Brain Res. Rev. 60, 226-242. doi: 10.1016/j.brainresrev.2008
71. Nicholson, B., and Verma, S. (2004). Comorbidities in chronic neuropathic pain. Pain Med. 5(Suppl. 1), S9-S27. doi: 10.1111/j.1526-4637.2004.04019.x
72. Niculescu, M. D., Craciunescu, C. N., and Zeisel, S. H. (2006). Dietary choline deficiency alters global and gene-specific DNA methylation in the developing hippocampus of mouse fetal brains. FASEB J. 20, 43-49. doi: 10.1096/fj.05-4707com
73. Numata, S., Ye, T., Herman, M., and Lipska, B. K. (2014). DNA methylation changes in the postmortem dorsolateral prefrontal cortex of patients with schizophrenia. Front. Genet. 5:280. doi: 10.3389/fgene.2014.00280
74. Ou, J. N., Torrisani, J., Unterberger, A., Provençal, N., Shikimi, K., Karimi, M., et al. (2007). Histone deacetylase inhibitor Trichostatin A induces global and gene-specific DNA demethylation in human cancer cell lines. Biochem. Pharmacol. 73, 1297-1307. doi: 10.1016/j.bcp.2006.12.032
75. Pang, Z. P., Melicoff, E., Padgett, D., Liu, Y., Teich, A. F., Dickey, B. F., et al. (2006). Synaptotagmin-2 is essential for survival and contributes to Ca2+ triggering of neurotransmitter release in central and neuromuscular synapses. J. Neurosci. 26, 13493-13504. doi: 10.1523/jneurosci.3519-06.2006
76. Pleger, B., Draganski, B., Schwenkreis, P., Lenz, M., Nicolas, V., Maier, C., et al. (2014). Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex. PLoS One 9:e85372. doi: 10.1371/journal.pone.0085372
77. Poh, K. W., Yeo, J. F., Stohler, C. S., and Ong, W. Y. (2012). Comprehensive gene expression profiling in the prefrontal cortex links immune activation and neutrophil infiltration to antinociception. J. Neurosci. 32, 35-45. doi: 10.1523/JNEUROSCI.2389-11.2012
78. Ramsahoye, B. H., Biniszkiewicz, D., Lyko, F., Clark, V., Bird, A. P., and Jaenisch, R. (2000). Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc. Natl. Acad. Sci. U S A 97, 5237-5242. doi: 10.1073/pnas.97.10.5237
79. Razin, A., and Riggs, A. D. (1980). DNA methylation and gene function. Science 210, 604-610. doi: 10.1126/science.6254144
80. Ruscheweyh, R., Willemer, C., Krüger, K., Duning, T., Warnecke, T., Sommer, J., et al. (2011). Physical activity and memory functions: an interventional study. Neurobiol. Aging 32, 1304-1319. doi: 10.1016/j.neurobiolaging.2009.08.001
81. Schmidt-Wilcke, T., Leinisch, E., Gänssbauer, S., Draganski, B., Bogdahn, U., Altmeppen, J., et al. (2006). Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain 125, 89-97. doi: 10.1016/j.pain.2006.05.004
82. Schmidt-Wilcke, T., Leinisch, E., Straube, A., Kämpfe, N., Draganski, B., Diener, H. C., et al. (2005). Gray matter decrease in patients with chronic tension type headache. Neurology 65, 1483-1486. doi: 10.1212/01.wnl.0000183067.94400.80
83. Schmidt-Wilcke, T., Luerding, R., Weigand, T., Jürgens, T., Schuierer, G., Leinisch, E., et al. (2007). Striatal grey matter increase in patients suffering from fibromyalgia-a voxel-based morphometry study. Pain 132(Suppl. 1), S109-S116. doi: 10.1016/j.pain.2007.05.010
84. Schwartz, N., Temkin, P., Jurado, S., Lim, B. K., Heifets, B. D., Polepalli, J. S., et al. (2014). Chronic pain. Decreased motivation during chronic pain requires long-term depression in the nucleus accumbens. Science 345, 535-542. doi: 10.1126/science.1253994
85. Seminowicz, D. A., Laferriere, A. L., Millecamps, M., Yu, J. S., Coderre, T. J., and Bushnell, M. C. (2009). MRI structural brain changes associated with sensory and emotional function in a rat model of long-term neuropathic pain. Neuroimage 47, 1007-1014. doi: 10.1016/j.neuroimage.2009.05.068
86. Seminowicz, D. A., Wideman, T. H., Naso, L., Hatami-Khoroushahi, Z., Fallatah, S., Ware, M. A., et al. (2011). Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function. J. Neurosci. 31, 7540-7550. doi: 10.1523/JNEUROSCI.5280-10.2011
87. Sharp, J., and Keefe, B. (2005). Psychiatry in chronic pain: a review and update. Curr. Psychiatry Rep. 7, 213-219. doi: 10.1007/s11920-005-0056-x
88. Shukla, S., Kavak, E., Gregory, M., Imashimizu, M., Shutinoski, B., Kashlev, M., et al. (2011). CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Nature 479, 74-79. doi: 10.1038/nature10442
89. Sibille, E., Arango, V., Galfalvy, H. C., Pavlidis, P., Erraji-Benchekroun, L., Ellis, S. P., et al. (2004). Gene expression profiling of depression and suicide in human prefrontal cortex. Neuropsychopharmacology 29, 351-361. doi: 10.1038/sj.npp.1300335
90. Stefani, G., and Slack, F. J. (2008). Small non-coding RNAs in animal development. Nat. Rev. Mol. Cell Biol. 9, 219-230. doi: 10.1038/nrm2347
91. Stein, R., Razin, A., and Cedar, H. (1982). In vitro methylation of the hamster adenine phosphoribosyltransferase gene inhibits its expression in mouse L cells. Proc. Natl. Acad. Sci. U S A 79, 3418-3422. doi: 10.1073/pnas.79.11.3418
92. Szyf, M. (1994). DNA methylation properties: consequences for pharmacology. Trends Pharmacol. Sci. 15, 233-238. doi: 10.1016/0165-6147(94)90317-4
93. Szyf, M. (2009). Epigenetics, DNA methylation and chromatin modifying drugs. Annu. Rev. Pharmacol. Toxicol. 49, 243-263. doi: 10.1146/annurev-pharmtox-061008-103102
94. Tagliazucchi, E., Balenzuela, P., Fraiman, D., and Chialvo, D. R. (2010). Brain resting state is disrupted in chronic back pain patients. Neurosci. Lett. 485, 26-31. doi: 10.1016/j.neulet.2010.08.053
95. Tajerian, M., Alvarado, S., Millecamps, M., Vachon, P., Crosby, C., Bushnell, M. C., et al. (2013). Peripheral nerve injury is associated with chronic, reversible changes in global DNA methylation in the mouse prefrontal cortex. PLoS One 8:e55259. doi: 10.1371/journal.pone.0055259
96. Tajerian, M., and Clark, J. D. (2015). The role of the extracellular matrix in chronic pain following injury. Pain 156, 366-370. doi: 10.1097/01.j.pain.0000460323.80020.9d
97. Tajerian, M., Leu, D., Zou, Y., Sahbaie, P., Li, W., Khan, H., et al. (2014). Brain neuroplastic changes accompany anxiety and memory deficits in a model of complex regional pain syndrome. Anesthesiology 121, 852-865. doi: 10.1097/ALN.0000000000000403
98. Tuck-Muller, C. M., Narayan, A., Tsien, F., Smeets, D. F., Sawyer, J., Fiala, E. S., et al. (2000). DNA hypomethylation and unusual chromosome instability in cell lines from ICF syndrome patients. Cytogenet. Cell Genet. 89, 121-128. doi: 10.1159/000015590
99. Vardimon, L., Kressmann, A., Cedar, H., Maechler, M., and Doerfler, W. (1982). Expression of a cloned adenovirus gene is inhibited by in vitro methylation. Proc. Natl. Acad. Sci. U S A 79, 1073-1077. doi: 10.1073/pnas.79.4.1073
100. Virok, D. P., Kis, Z., Szegedi, V., Juhász, G., Zvara, A. Jr., Müller, G., et al. (2011). Functional changes in transcriptomes of the prefrontal cortex and hippocampus in a mouse model of anxiety. Pharmacol. Rep. 63, 348-361. doi: 10.1016/s1734-1140(11)70501-1
101. Walton, E., Liu, J., Hass, J., White, T., Scholz, M., Roessner, V., et al. (2014). MB-COMT promoter DNA methylation is associated with working-memory processing in schizophrenia patients and healthy controls. Epigenetics 9, 1101-1107. doi: 10.4161/epi.29223
102. Weaver, I. C., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., et al. (2004a). Epigenetic programming by maternal behavior. Nat. Neurosci. 7, 847-854. doi: 10.1038/nn1276
103. Weaver, I. C., Champagne, F. A., Brown, S. E., Dymov, S., Sharma, S., Meaney, M. J., et al. (2005). Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J. Neurosci. 25, 11045-11054. doi: 10.1523/jneurosci.3652-05.2005
104. Weaver, I. C., D'Alessio, A. C., Brown, S. E., Hellstrom, I. C., Dymov, S., Sharma, S., et al. (2007). The transcription factor nerve growth factor-inducible protein a mediates epigenetic programming: altering epigenetic marks by immediate-early genes. J. Neurosci. 27, 1756-1768. doi: 10.1523/jneurosci.4164-06.2007
105. Weaver, I. C., Diorio, J., Seckl, J. R., Szyf, M., and Meaney, M. J. (2004b). Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites. Ann. N Y Acad. Sci. 1024, 182-212. doi: 10.1196/annals.1321.099
106. Weaver, I. C., Meaney, M. J., and Szyf, M. (2006). Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proc. Natl. Acad. Sci. U S A 103, 3480-3485. doi: 10.1073/pnas.0507526103
107. Wood, S. H., Craig, T., Li, Y., Merry, B., and de Magalhaes, J. P. (2013). Whole transcriptome sequencing of the aging rat brain reveals dynamic RNA changes in the dark matter of the genome. Age (Dordr.) 35, 763-776. doi: 10.1007/s11357-012-9410-1
108. Yoder, J. A., Walsh, C. P., and Bestor, T. H. (1997). Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 13, 335-340. doi: 10.1016/s0168-9525(97)01181-5
109. Zhao, X., Tang, Z., Zhang, H., Atianjoh, F. E., Zhao, J. Y., Liang, L., et al. (2013). A long noncoding RNA contributes to neuropathic pain by silencing Kcna2 in primary afferent neurons. Nat. Neurosci. 16, 1024-1031. doi: 10.1038/nn.3438
110. Ziller, M. J., Gu, H., Müller, F., Donaghey, J., Tsai, L. T.-Y., Kohlbacher, O., et al. (2013). Charting a dynamic DNA methylation landscape of the human genome. Nature 500, 477-481. doi: 10.1038/nature12433