Table.

Diagnostic Biomarkers for Hand-Related Chronic Pain Conditions

Condition	Molecular Biomarkers (Inflammatory Markers, Metabolites, Exosome Contents)	Nonmolecular Biomarkers (HRV, structural MRI, functional MRI, EEG, skin biopsy)
CRPS	↑Osteoprotegerin ↓ Bilirubin + IgG antibodies∗ ↑ Glutamate, aspartate ↓ Tryptophan, arginine ↑ miR-21-3p, miR-146a, and miR-146b	↓ IBI, SD, RMSSD ↑ LF:HF-HRV ↓ Dorsal insula, left orbitofrontal complex, cingulate cortex thickness ↓ Functional connections in the forebrain areas related to motor, affective, cognitive, and pain inhibitory/modulatory processes ↑ TNF-α, IL-6, mast cell accumulation||
Osteoarthritis	↑IL-7, IL-8, IL-10, IL-12, IL-13, interferon-γ, C-reactive protein, C-reactive protein metabolite, C-X-C motif chemokine ligand 10, MMP-3 MMP-13, tissue inhibitor of metalloproteinase-1, C-terminal cross-linked telopeptide of type II, cartilage oligomeric matrix protein, brain-derived neurotrophic factor ↓ IL-1b ↑ Fructose, citrate ↓O-acetylcarnitine, N-phenylacetylglycine, methionine, ethanol, creatine, malate, ethanolamine, 3-hydroxybutyrate, hexanoylcarnitine† ↓ arginine ↓ Production TNF-α, IL-6, prostaglandin-E2, nitric oxide ↑ Production IL-10	↓ Prefrontal motor cortex gray matter volume ↓ Spontaneous brain activity in the prefrontal limbic area ↓ Functional connectivity between the dorsolateral prefrontal cortex and the pain matrix¶
Neuropathic pain	↑ Haptoglobin isoforms‡ ↓ Transthyretin and α2 macroglobulin‡ ↑ Fos, Tp53, Csk, and Map2k2‡ ↑ Phosphocholine, alanine, and taurine§ ↑ Ccl3 ↑ Complement 5a, intercellular adhesion molecule 1‡	↓ RMSSD ↑ Small, unmyelinated fibers

^∗Activate β2 adrenergic, M2 muscarinic receptors.

^†Synovial fluid, rather than serum, for sample.

^‡Mouse model.

^§Urine, rather than serum, for sample.

^||Acute, not chronic, CRPS.

^¶Pediatric population.