| First Author | Chen G | Year | 2015 |
| Journal | J Clin Invest | Volume | 125 |
| Issue | 8 | Pages | 3226-40 |
| PubMed ID | 26168219 | Mgi Jnum | J:224522 |
| Mgi Id | MGI:5688216 | Doi | 10.1172/JCI80883 |
| Citation | Chen G, et al. (2015) Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-beta secretion. J Clin Invest 125(8):3226-40 |
| abstractText | Neuropathic pain remains a pressing clinical problem. Here, we demonstrate that a local, intrathecal (i.t.) injection of bone marrow stromal cells (BMSCs) following lumbar puncture alleviates early- and late-phase neuropathic pain symptoms, such as allodynia and hyperalgesia, for several weeks in murine chronic constriction injury (CCI) and spared nerve injury models. Moreover, i.t. BMSCs reduced CCI-induced spontaneous pain and axonal injury of dorsal root ganglion (DRG) neurons and inhibited CCI-evoked neuroinflammation in DRGs and spinal cord tissues. BMSCs secreted TGF-beta1 into the cerebrospinal fluid, and neutralization of TGF-beta1, but not IL-10, reversed the analgesic effect of BMSCs. Conversely, i.t. administration of TGF-beta1 potently inhibited neuropathic pain. TGF-beta1 acted as a powerful neuromodulator and rapidly (within minutes) suppressed CCI-evoked spinal synaptic plasticity and DRG neuronal hyperexcitability via TGF-beta receptor 1-mediated noncanonical signaling. Finally, nerve injury upregulated CXCL12 in lumbar L4-L6 DRGs, and this upregulation caused migration of i.t.-injected BMSCs to DRGs through the CXCL12 receptor CXCR4, which was expressed on BMSCs. BMSCs that migrated from the injection site survived at the border of DRGs for more than 2 months. Our findings support a paracrine mechanism by which i.t. BMSCs target CXCL12-producing DRGs to elicit neuroprotection and sustained neuropathic pain relief via TGF-beta1 secretion. |
