{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:25:50Z","timestamp":1789683950190,"version":"4.0.1"},"reference-count":105,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH RO1 grant","award":["NS107569"],"award-info":[{"award-number":["NS107569"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Patients with systemic lupus erythematosus (SLE) often suffer from chronic pain due to a lack of effective and safe analgesics. In this study, we investigated the role of spinal TLR7 in the pathogenesis of chronic pain using female MRL lupus prone (MRL\/lpr) mice, a SLE mouse model. We found that from 11 weeks of age, MRL\/lpr mice exhibited thermal hypersensitivity in the hind paw, which reached plateau between 14 and 16 weeks. MRL\/lpr mice with thermal hypersensitivity had increased expression of TLR7 in the spinal dorsal horn. TLR7 was located in microglia in this region. Intrathecal administration of a TLR7 antagonist attenuated the thermal hypersensitivity in MRL\/lpr mice, while administration of the TLR7 agonist induced thermal hypersensitivity in control mice. Pharmacological activation of spinal TLR7 in control mice recapitulated molecular, synaptic, and cellular changes in the spinal dorsal horn of MRL\/lpr mice with thermal hyperalgesia. These alterations included activation of microglia and astrocytes, increased production of IL-1\u03b2 and IL-18, upregulated expression of N-type voltage-gated calcium channels (Cav2.2), enhanced glutamatergic synaptic activity, and elevated neuronal activation. Our findings suggest that targeting TLR7 or downstream effectors may represent a promising strategy to alleviate chronic pain induced by SLE.<\/jats:p>","DOI":"10.3390\/cells15010020","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T11:43:31Z","timestamp":1766403811000},"page":"20","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Spinal Microglial TLR7 Activation Drives Hyperalgesia in a Lupus Mouse Model via Upregulation of IL-1\u03b2, IL-18, and Cav2.2 and Enhanced Glutamatergic Synaptic Activity"],"prefix":"10.3390","volume":"15","author":[{"given":"Saumya","family":"Bipin","sequence":"first","affiliation":[{"name":"Department of Basic Sciences, California Northstate University College of Medicine, 9700 W Taron Drive, Elk Grove, CA 95757, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viacheslav","family":"Viatchenko-Karpinski","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Mercer University School of Medicine, Macon, GA 31207, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, California Northstate University College of Medicine, 9700 W Taron Drive, Elk Grove, CA 95757, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujin","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, California Northstate University College of Medicine, 9700 W Taron Drive, Elk Grove, CA 95757, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2062-2782","authenticated-orcid":false,"given":"Han-Rong","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, California Northstate University College of Medicine, 9700 W Taron Drive, Elk Grove, CA 95757, USA"},{"name":"Department of Biomedical Sciences, Mercer University School of Medicine, Macon, GA 31207, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1136\/ard.37.2.121","article-title":"Systemic lupus erythematosus. 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