Pathogenetic mechanisms in FMS
| Genetic factors |
| Linkage to the chromosome 17p11.2-q11.2 region |
| Linkage to serotonin receptor 2A region of chromosome 13 |
| Linkage to HLA region of chromosome 6 |
| Polymorphisms associated with the serotonin transporter (5-HTT) gene regulatory region |
| Linkage to catecholamine methyltransferase (COMT) genes |
| Negative association with the COMT val158met polymorphism |
| Association with dopamine-D-3 receptor (DRD3) Ser9Gly polymorphism |
| Single nucleotide polymorphisms (SNPs) involving gamma-aminobutyric acid receptor subunit beta 3 (GABRB3), trace amine receptors (TAAR1), and guanylate binding protein 1 (GBP1) |
| Neural processes |
| Altered heat and cold thresholds |
| Reduced tolerance for pain and nociceptive reflex threshold |
| Smaller than normal brain gray matter volumes |
| Less connectivity within the brain’s pain inhibitory network |
| Chiari malformation |
| Neuroinflammation |
| High serum IL-6 |
| High serum TNF |
| High plasma monocyte chemoattractant protein-1 (MCP-1/CCL2) and eotaxin (CCL) |
| High serum and CSF levels of IL-8 (CXCL8) |
| Increased plasma levels of IL-17A |
| Increased CSF levels of SP and nerve growth factor |
| Increased skin mast cells |
| Oxidative stress |
| Lower total nitrite levels |
| Higher serum prolidase activity, |
| Higher total oxidative status (TOS) |
| Reduced level of coenzyme Q10 (CoQ10) |
| High level of reactive oxygen species (ROS) |