Table 1.
Epigenetic Modification | Effect | Reference |
---|---|---|
DNA methylation | Hypomethylation of two CpG dinucleotides in the promoter of CALCA in sporadic migraine patients | [65] |
Low DNA methylation trend in the promoter of RAMP1 in migraineurs with higher methylation levels in patients with family history, lower methylation in female migraineurs | [68] | |
Histone modifications | Blockade of the CGRP receptor by HDAC6 inhibition, resulting in reversing of NTG-induced chronic allodynia in mice | [79] |
Co-expression of CGRP-induced abnormal histone modifications, including H3K27me3, with proinflammatory mediators in the spinal dorsal horn and cultured microglial cells | [80,81,84] | |
Altered HDAC2 enrichment in over 1200 genes in microglial cells by CGRP, with most of the genes belonging to immune- and inflammation-related pathways | [18] | |
H3K9ac signal in rat cells expressing CALCA, but lack of such signals in cells non-expressing CALCA; that effect of histone acetylation required DNA methylation to be manifested | [14] | |
CGRP-induced acetylation of H3K9 in astrocytes linked with neuroinflammation in rats with neuropathic pain and H3K9ac enrichment on gene promoters in astroglial cells | [87] | |
Micro RNAs | CGRP plasma levels positively correlated with the expression of miR-382-5p, and miR-34a-5p in plasma of migraineurs | [93] |
Overexpression of miR-30a caused downregulation of CALCA, while knockdown of miR-30 resulted in CALCA upregulation; miR-30a might bind CALCA in its 3′-UTR to degrade it | [95] | |
miR-125a-3p regulated CGRP in inflammatory pain; | [99] | |
increased levels of CGRP induced by NTG were abolished by miR-155-5p antagomir; miR-155-5p agomir aggravated neuroinflammation and central sensitization and increased CGRP expression | [100] | |
Circular RNAs | CGRP promoted mmu_circRNA_007893 expression in RAW264.7 macrophages | [107] |
CGRP regulated migraine-related FOSL2 expression mediated by miR-504-3p sponging by mmu_circRNA_003795 | [109,112] | |
Aberrant expression of mm9_circ_009056 circRNA in CGRP-induced MC3T3 cells | [113] | |
Long non-coding RNAs | Gm14461 lncRNA knockdown increased, whereas Gm14461 overexpression decreased CGRP levels in primary mouse trigeminal ganglion neurons | [116] |
Overexpression of lncRNA-NONRATT021203.2 in rats with induced CIP; lncRNA-NONRATT021203.2 targeted CXCL9, increased in CIP rats; CXCL9 was expressed in the CGRP-positive dorsal root ganglion neurons that colocalized with lncRNA-NONRATT021203.2 | [119] |
1 Abbreviations: CGRP, calcitonin gene-related peptide; CALCA, calcitonin-related peptide alpha; RAMP1, receptor activity-modifying protein 1; HDAC6, histone deacetylase 6, NTG, nitroglycerin; H3K27me3, trimethylation of histone H3 at lysine 27; H3K9ac, histone H3 acetylated at lysine 9; FOSL2, FOS-like 2 AP-1 transcription factor subunit; CIP, cancer-induced pain; CXCL9, C-X-C motif chemokine ligand 9.