TABLE 2.

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)