Bone marrow stromal cells produce long-term pain relief in rat models of persistent pain

Wei Guo, Hu Wang, Shiping Zou, Ming Gu, Mineo Watanabe, Feng Wei, Ronald Dubner, George Huang, Ke Ren

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Chronic pain conditions are difficult to treat and are major health problems. Bone marrow stromal cells (BMSCs) have generated considerable interest as a candidate for cell-based therapy. BMSCs are readily accessible and are easy to isolate and expand ex vivo. Clinical studies show that direct injection of BMSCs does not produce unwanted side effects and is well tolerated and safe. Here, we show that a single systemic (intravenous) or local injection (into the lesion site) of rat primary BMSCs reversed pain hypersensitivity in rats after injury and that the effect lasted until the conclusion of the study at 22 weeks. The pain hypersensitivity was rekindled by naloxone hydrochloride, an opioid receptor antagonist that acts peripherally and centrally, when tested at 1-5 weeks after BMSC infusion. In contrast, naloxone methiodide, a peripherally acting opioid receptor antagonist, only rekindled hyperalgesia in the first 3 weeks of BMSC treatment. Focal downregulation of brainstem mu opioid receptors by RNA interference (RNAi) reversed the effect of BMSCs, when RNAi was introduced at 5- but not 1-week after BMSC transplantation. Thus, BMSCs produced longterm relief of pain and this effect involved activation of peripheral and central opioid receptors in distinct time domains. The findings prompt studies to elucidate the cellular mechanisms of the BMSC-induced pain relieving effect and translate these observations into clinical settings.

Original languageEnglish (US)
Pages (from-to)1294-1303
Number of pages10
JournalStem Cells
Volume29
Issue number8
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

Fingerprint

Mesenchymal Stromal Cells
Pain
Narcotic Antagonists
RNA Interference
Hypersensitivity
Injections
mu Opioid Receptor
Hyperalgesia
Opioid Receptors
Naloxone
Cell- and Tissue-Based Therapy
Bone Marrow Transplantation
Chronic Pain
Brain Stem
Down-Regulation
Health
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Guo, W., Wang, H., Zou, S., Gu, M., Watanabe, M., Wei, F., ... Ren, K. (2011). Bone marrow stromal cells produce long-term pain relief in rat models of persistent pain. Stem Cells, 29(8), 1294-1303. https://doi.org/10.1002/stem.667

Bone marrow stromal cells produce long-term pain relief in rat models of persistent pain. / Guo, Wei; Wang, Hu; Zou, Shiping; Gu, Ming; Watanabe, Mineo; Wei, Feng; Dubner, Ronald; Huang, George; Ren, Ke.

In: Stem Cells, Vol. 29, No. 8, 01.08.2011, p. 1294-1303.

Research output: Contribution to journalArticle

Guo, W, Wang, H, Zou, S, Gu, M, Watanabe, M, Wei, F, Dubner, R, Huang, G & Ren, K 2011, 'Bone marrow stromal cells produce long-term pain relief in rat models of persistent pain', Stem Cells, vol. 29, no. 8, pp. 1294-1303. https://doi.org/10.1002/stem.667
Guo, Wei ; Wang, Hu ; Zou, Shiping ; Gu, Ming ; Watanabe, Mineo ; Wei, Feng ; Dubner, Ronald ; Huang, George ; Ren, Ke. / Bone marrow stromal cells produce long-term pain relief in rat models of persistent pain. In: Stem Cells. 2011 ; Vol. 29, No. 8. pp. 1294-1303.
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