Table 1 Low back pain markers

BDKRB1

G-protein coupled receptor that binds to bradykinin and is synthesized in pathophysiologic conditions such as inflammation, trauma, burns, shock, and allergy. Ultimately results in chronic and acute inflammation

^29,390

CGRP (CALCA or CALCB)

Neuropeptide that is involved with pain signaling, vasodilation, neurogenic inflammation, and modulation of autonomic nervous system

^{29,128,146,276,277,278,279,280,330,390,391,392,393,394,395}

CALCA: accounts for >90% of total CGRP expression in most tissues. Primarily expressed in CNS and PNS

CALCB: Mainly expressed in enteric nervous system.

COMT

Enzyme involved inactivation of catecholamine neurotransmitters transmitters including dopamine, epinephrine and norepinephrine

^{29,87,390,396}

IL-6

Pleiotrophic cytokine that plays an important role in inflammation, immune response, etc.

^{29,279,330,397,398,399,400}

TMEM100

Involved in vascular development

³⁹⁷

VEGF-A

Growth factor in PDGF/VEGF family. Heparin-binding protein that induces proliferation and migration of vascular endothelial cells

^401,402

CD31 (PECAM1)

Protein found in endothelial cell junctions and is likely involved in leukocyte migration, angiogenesis and integrin activation

^195,401,402

IL-1B

Produced by activated macrophages then activated by caspase 1. important mediator of inflammatory response and other cellular responses such as proliferation, differentiation and apoptosis

^{165,330,394,398,399,400,401,402}

IL-17

Pro-inflammatory cytokine produced by T-helper 17 cells

^400,402,403

TAC1

Precursor protein for Substance P

^146,404,405

SubP (Substance P)

Neuropeptide associated with pain and noxious stimuli

^{280,393,398,404}

NPY

Neuropeptide and neurotransmitter synthesized by GABAergic neurons involved in various physiological and homeostatic processes in both the central and peripheral nervous system

^219,395,406

BDNF

Neurotrophin that primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons

^{29,165,401,405,407}

NGF

Neurotrophic factor and neuropeptide with nerve growth stimulating activity and the complex is involved in the regulation of growth and the differentiation of sympathetic and certain sensory neurons.

^{165,279,330,390,401,405,408}

NGFR (p75NTR)

Non-specific neurotrophin receptor

^{195,333,409,410}

NTRK1 (TrkA)

Receptor for NGF. Activation leads to cell differentiation, and may play a role in specifying sensory neuron subtypes

^{165,195,333,405,409}

NTRK2 (TrkB)

Receptor for BDNF.

^405,410

ATF3

Transcription factor involved in physiological stress response. Marker of DRG neuron injury, Androgen signaling repressor

^330,408,411

TNF

Proinflammatory cytokine mainly secreted by macrophages but can be produced by other cell types.

^{128,165,253,279,330,398,400}

TRPV1

Non-selective cation channel activated by noxious stimuli including heat. Thought to function as a transducer of painful thermal stimuli

^{146,280,333,392,399,412,413}

TRPV4

A2 + -permeable, nonselective cation channel that is thought to be involved multiple physiological functions. Activated by osmotic, mechanical, chemical, and thermal cues

^399,414,415

IL-8 (CXCL8)

Cytokine secreted by mononuclear macrophages, neutrophils, eosinophils, T lymphocytes, epithelial cells, and fibroblasts. It functions as a chemotactic factor by guiding the neutrophils to the site of infection

^{3,128,399,416,417}

UCHL1 (PGP9.5)

Enzyme involved in hydrolysis of peptide bond at C-terminal glycine of ubiquitin. Specifically expressed in neurons and in cell of the diffuse neuroendocrine system

^{276,277,395,401,418}

GAP43

Involved in neuronal growth, development and regeneration. Highly expressed in growth cones. Involved in the formation and strengthening of synapses

^195,330,408

RAMP1

Required to transport calcitonin-receptor-like receptor (CALCRL) to the plasma membrane

³⁹¹

CALCRL

G-protein coupled receptor related to calcitonin receptor. Associated with RAMPs to produce different receptors. Ex: RAMP1 and CALCRL produces a CGRP receptor

^391,419

NK1R (TAC1R or SPR)

G-protein coupled receptor found in the nervous system activated by substance p

^398,405

NTN1

Thought to be involved in axon guidance and cell migration during development

^224,420

SCN8A (Nav1.6)

Sodium channel found in various tissues including neurons, heart and glial cells

^421,422

SCN9A (Nav1.7)

Sodium channel found in various neural tissues

^278,281,423

SCN10A (Nav1.8)

Sodium channel found in DRG and associated with pain and neuropsychiatric disorders

^418,423

AIF1 (IBA1)

Induced by cytokines and interferons and protein that binds actin and calcium. induced by cytokines and interferon and may promote macrophage activation and growth of vascular smooth muscle cells and T-lymphocytes

^235,279,395

GFAP

Major intermediate filaments found in mature astrocytes. Marker used to distinguish astrocytes from other glial cells

^{128,235,279,282,394,395}