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Grafted human telomerase reverse transcriptase\u2013immortalized bone marrow mesenchymal stromal cells (hTERT-BMSCs) with inducible galanin (GAL) expression have been considered to be a potentially safe and controllable approach for the alleviation of chronic pain. Therefore, in this study, we aimed to assess the feasibility of hTERT-BMSCs\/Tet-on\/GAL cells secreting GAL under the transcriptional control of doxycycline (Dox) for controllable pain relief. After transplanted into the subarachnoid space of neuropathic rats induced by spared nerve injury of sciatic nerve, their analgesic actions were investigated by behavioral tests. The results showed that the pain-related behaviors, mechanical allodynia, and thermal hyperalgesia were significantly alleviated during 1 to 7 weeks after grafts of hTERT-BMSCs\/Tet-on\/GAL cells without motor incoordination. Importantly, these effects could be reversed by GAL receptor antagonist M35 and regulated by Dox induction as compared with control. Moreover, the GAL level in cerebrospinal fluid and spinal GAL receptor 1 (GalR1) expression were correlated with Dox administration, but not GAL receptor 2 (GalR2). Meanwhile, spinal protein kinase M\u03b6 (PKM\u03b6) expression was also inhibited significantly. Taken together, these data suggest that inducible release of GAL from transplanted cells was able to produce controllable pain relief in neuropathic rats via inhibiting the PKM\u03b6 activation and activating its GalR1 rather than GalR2. This provides a promising step toward a novel stem cell\u2013based strategy for pain therapy.<\/jats:p>","DOI":"10.1177\/09636897221103861","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T07:49:58Z","timestamp":1655797798000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Immortalized Bone Mesenchymal Stromal Cells With Inducible Galanin Expression Produce Controllable Pain Relief in Neuropathic Rats"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8369-6557","authenticated-orcid":false,"given":"Ke","family":"An","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingpeng","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, 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