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Department of Anesthesiology Department of Anesthesiology
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Immunity in Neuropathic Pain

neuroimmune contact Node of Ranvier

About Neuropathic Pain (NP)

Neuropathic pain (NP) is a devastating chronic pain state not treatable by current analgesics. NP may arise spontaneously (e.g. shooting pain) or from light (e.g. tough) stimuli in people suffering from PNS/CNS damage caused by physical trauma, neurodegenerative and autoimmune disease, metabolic disease (e.g. diabetes), chemotherapy, viral pathogens, etc.

Our Research

We have established many mechanisms of neuro-inflammation involved in the development of NP. Thus, we identified an inflammatory cytokine TNF-α as a spinal disc component and a therapeutic target in radiculopathy (1). By establishing the ability of TNF-α to undergo axonal transport (2), we proposed a new mechanism of CNS plasticity and remote neuroinflammation after peripheral lesions.

Our work was the first to implicate metalloproteinases (reviewed in 3, 4) and myelin autoantigens (5–7) as pain mediators. Our current research suggests that the release of the algesic fragments of myelin basic protein (MBP) from the intact myelin sheath protein contributes to autoimmune pathogenesis of NP, especially in females (micrograph). Our long-term aim is to develop novel, non-addictive therapeutic strategies in treating chronic neuropathic pain.

Representative Papers

  1. Igarashi T, Kikuchi S, Shubayev V, Myers RR: 2000 Volvo Award Winner in Basic Science Studies: Exogenous TNF-α mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats, Spine, 25 (23): 2975-80, 2000.
  2. Shubayev VI, Myers RR: Axonal transport of TNF-α in painful neuropathy: Distribution of ligand tracer and TNF receptors, J. Neuroimmunology, 114(1-2): 48-56, 2001.
  3. Myers RR, Campana WM, Shubayev VI: The role of neuroinflammation in neuropathic pain: mechanisms and therapeutic targets, Drug Discovery Today, 11(1/2): 8-20, 2006.
  4. Remacle AG, Kumar S, Motamedchaboki K, Clepak P, Hullugundi SK, Dolkas J, Shubayev VI, Strongin AY: MMP proteolysis of the extracellular loop of voltage-gated sodium channels and potential alterations in pain signaling, J Biol Chem, 290 (38): 22939-44, 2015.
  5. Liu H, Shiryaev SA, Chernov AV, Kim Y, Shubayev I, Remacle AG, Baranovskaya S, Golubkov VS, Strongin AY, Shubayev VI: Immunodominant fragments of myelin basic protein initiate T cell-dependent pain, J. Neuroinflammation, 9 (1): 119, 2012.
  6. Ko JS, Eddinger KA, Angert M, Chernov AV, Dolkas J, Strongin AY, Yaksh TL, Shubayev VI: Spinal activity of IL-6 mediates mechanical allodynia induced by myelin basic protein, Brain Behav. Immun., 56: 378-89, 2016.
  7. Hong SH, Remacle AG, Shiryaev SA, Choi WJ, Hullugundi SK, Dolkas J, Angert M, Nishihara T, Yaksh TL, Strongin AY, Shubayev VI: Reciprocal relationship between membrane type 1 matrix metalloproteinase and the algesic peptides of myelin basic protein contributes to chronic neuropathic pain. Brain Behav Immun, 60: 282-92, 2017.