Neuroimmune modulation of pain and regenerative pain medicine
Thomas Buchheit, … , Jianguo Cheng, Ru-Rong Ji
Thomas Buchheit, … , Jianguo Cheng, Ru-Rong Ji
Published April 6, 2020
Citation Information: J Clin Invest. 2020;130(5):2164-2176. https://doi.org/10.1172/JCI134439.
View: Text | PDF
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

×

Figure 2

Preclinical models of cellular and cell-free exosome therapies for chronic pain.

Options: View larger image (or click on image) Download as PowerPoint
Preclinical models of cellular and cell-free exosome therapies for chron...
(i) Single systemic or local injection of BMSCs can reverse mechanical allodynia by in vivo immune interactions and activation of monocytes. (ii) Intrathecally injected BMSCs migrate to meninges of injured DRG neurons and spinal cord dorsal horn via a CXCL12/CXCR4 homing mechanism. TGF-β1 secretion by BMSCs confers potent long-term pain relief by activation of the neuronal TGF-β receptor (TGF-βR). (iii) Intrathecal injection of exosomes derived from human umbilical cord mesenchymal cells can serve as cell-free therapy for neuropathic pain. (iv) Transplantation of embryonic cortical GABAergic interneuron precursors from the medial ganglionic eminence (MGE) into the spinal cord leads to the development of inhibitory neurons. Furthermore, these GABAergic neurons integrate into spinal nociceptive circuits, mediating pain relief by release of GABA that acts on host-transplant inhibitory synaptic circuits.