Neuroimmune modulation of pain and regenerative pain medicine
Thomas Buchheit, Yul Huh, William Maixner, Jianguo Cheng, Ru-Rong Ji
Thomas Buchheit, Yul Huh, William Maixner, Jianguo Cheng, Ru-Rong Ji
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Review

Neuroimmune modulation of pain and regenerative pain medicine

Abstract

Regenerative pain medicine, which seeks to harness the body’s own reparative capacity, is rapidly emerging as a field within pain medicine and orthopedics. It is increasingly appreciated that common analgesic mechanisms for these treatments depend on neuroimmune modulation. In this Review, we discuss recent progress in mechanistic understanding of nociceptive sensitization in chronic pain with a focus on neuroimmune modulation. We also examine the spectrum of regenerative outcomes, including preclinical and clinical outcomes. We further distinguish the analgesic mechanisms of regenerative therapies from those of cellular replacement, creating a conceptual and mechanistic framework to evaluate future research on regenerative medicine.

Authors

Thomas Buchheit, Yul Huh, William Maixner, Jianguo Cheng, Ru-Rong Ji

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Figure 3

Clinically used blood-derived and cell-derived pain therapies and their mechanisms of action via production of therapeutic mediators.

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Clinically used blood-derived and cell-derived pain therapies and their ...
(A) PRP contains (a) α-granule–derived growth factors such as PDGF, TGF-β, and HGF, as well as TIMP-1 and TIMP-2 and (b) monocyte-derived factors including TGF-β, FGF, and IGF. ACS provides factors including IL-1 receptor antagonist (IL-1Rα), IL-4, IL-10, and TGF-β. MSCs have been found in clinical treatments to alter macrophage phenotypes, leading to direct and indirect production of IL-10 and TGF-β. MSCs also produce TSG-6 to inhibit inflammation and promote wound healing. Blood- and cell-derived therapies could also contain exosomes.(B) Common therapeutic mediators and mechanisms of action include (a) control of neuroinflammation, (b) tissue repair, and (c) pro-resolution processes. Notably, PRP, ACS, and MSCs may also contain or produce SPMs that produce multiple beneficial effects. ACS, autologous conditioned serum; MSC, mesenchymal stromal cells; PRP, platelet-rich plasma; SPM, specialized pro-resolving mediators.