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
 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)