Abstract
Current treatments for chronic pain, such as inflammatory pain, neuropathic pain, and cancer pain are insufficient and cause severe side effects. Mounting evidence suggests that neuroinflammation in the peripheral and central nervous system (PNS and CNS) plays a pivotal role in the genesis and maintenance of chronic pain. Characteristic features of neuroinflammation in chronic pain conditions include infiltration of immune cells into the PNS [e.g., the sciatic nerve and dorsal root ganglion (DRG)], activation of glial cells such as microglia and astrocytes in the CNS (spinal cord and brain), and production and secretion of pro-inflammatory cytokines and chemokines [TNF, interleukin (IL)-1β, IL-6, CCL2, and CXCL1]. Recent studies suggest that bone marrow stem cells or bone marrow stromal cells (BMSCs) produce powerful analgesic effects in animal models of inflammatory pain, neuropathic pain, and cancer pain. We recently demonstrated that intrathecal injection of BMSCs resulted in a long-term relief of neuropathic pain for several weeks after peripheral nerve injury. Strikingly, this analgesic effect is mediated by the anti-inflammatory cytokine transforming growth factor beta secreted from BMSCs. Additionally, BMSCs exhibit potent modulation of neuroinflammation, by inhibiting monocyte infiltration, glial activation, and cytokine/chemokine production in the DRG and spinal cord. Thus, BMSCs control chronic pain by regulation of neuroinflammation in the PNS and CNS via paracrine signaling. In this review, we discuss the similar results from different laboratories of remarkable anti-nociceptive efficacy of BMSCs in animal and clinical studies. We also discuss the mechanisms by which BMSCs control neuroinflammation and chronic pain and how these cells specifically migrate to damaged tissues.
Highlights
Whereas acute pain can bring attention to the body of possible injuries and is normally a protective sensation, chronic pain does not convey any useful information and has no biological benefits
Recent studies have revealed the therapeutic potential of bone marrow stromal cells/bone mesenchymal stem cells (BMSCs) for chronic pain [11,12,13,14]
Intravenous injection of BMSCs in rats reduced the damage of the intestinal mucosal barrier, led to the down-regulation of zona occludens 1 expression, and reduced the intestinal damage mediated by a TNFα-mediated mechanism [40]
Summary
Whereas acute pain can bring attention to the body of possible injuries and is normally a protective sensation, chronic pain does not convey any useful information and has no biological benefits It only gives people a feeling of discomfort but does not play an active role in wound healing. The production of glial and pro-inflammatory mediators (e.g., cytokines, chemokines, trophic factors, neurotransmitters, and lipid mediators) modulates pain sensitivity, with persistent glial and immune cell activation and interaction with neurons leading to the development of peripheral and central sensitization, and induction of chronic pain conditions. Targeting activated astrocyte signaling through connexin-43 and CXCL1 inhibition has demonstrated the ability to reverse established chronic neuropathic pain following peripheral nerve injury [5, 9]. By protecting the body from bacterial and viral infection, PRLMs are poised as one of the most effective treatments for preventing surgical or trauma-induced chronic pain [3, 10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
