• Matthew Meroney, Joshua Winegar, Holden Brown, Mark Bender, Scott Smith, and Rene Przkora.
• Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, 32610, USA. mmeroney@anest.ufl.edu.
• Curr Pain Headache Rep. 2022 Feb 1; 26 (2): 121-127.

Purpose Of ReviewThis narrative review examines stem cell therapy and its effect on opioid therapy in neuropathic pain.Recent FindingsStem cell therapy has shown promise in neuropathic pain and opioid tolerance, with a notable common pathway (the P2X4 receptor). Opioid therapy frequently has poor efficacy in patients who suffer from neuropathic pain. There is evidence that the presence of neuropathic pain itself causes changes to the opioid receptor, decreasing the therapeutic potential of this modality. The efficacy of opioid therapy is further decreased in this patient population after chronic opioid exposure, which leads to opioid tolerance and in some cases opioid-induced hyperalgesia. There is growing evidence that stem cell therapy has potential to treat neuropathic pain and may simultaneously decrease opioid tolerance and hyperalgesia. Opioid-induced hyperalgesia occurs via mu-opioid receptor-dependent expression of P2X4 receptors on microglia. Intrathecal stem cell therapy provides analgesic properties due to the significant reduction of P2X4R expression in spinal cord microglia, thereby directly decreasing chronic neuropathic pain.© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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