{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:50:21Z","timestamp":1785466221554,"version":"3.56.0"},"reference-count":83,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,30]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by persistent pain. The mechanisms underlying pain in SCD are poorly understood, and opioids remain the primary treatment, despite their severe side effects. Here, we investigated the contribution of lysophosphatidic acid (LPA), an endogenous pronociceptive lipid mediator, to chronic pain in SCD using humanized transgenic homozygous Berkeley mice that express &amp;gt;99% human sickle hemoglobin (HbSS) and control HbAA mice that express normal human hemoglobin A. Hyperalgesia in HbSS mice was associated with an increase in both plasma level of LPA and expression of LPA receptor 1 (LPA1R) mRNA in L1 to L5 dorsal root ganglion (DRG). Blocking LPA synthesis with BI-2545, or blocking LPA1R function with small interfering RNA (siRNA) or the LPA1R antagonist, AM966, reversed mechanical and heat hyperalgesia in HbSS mice. LPA also produced acute mechanical and heat hyperalgesia in HbAA mice, which resulted from the sensitization of C-fiber nociceptors. In HbSS mice, hyperalgesia was associated with sensitization of nociceptive DRG neurons. Nociceptors from hyperalgesic HbSS mice had lower rheobase, more positive resting membrane potential, and higher frequency of action potential. Although no changes were found in the values of inward currents in nociceptors of HbSS mice compared with HbAA mice, outward-inactivating and noninactivating currents were reduced, indicating the importance of potassium channels to sensitization in SCD. All these parameters were normalized by pretreatment of HbSS mice with LPA1R siRNA. Our results suggest that LPA signaling may be a promising target for treating pain in SCD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025031738","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T17:11:37Z","timestamp":1778692297000},"page":"623-633","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":1,"title":["Chronic pain in sickle cell disease: a role for lysophosphatidic acid"],"prefix":"10.1182","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9828-9081","authenticated-orcid":false,"given":"Viacheslav","family":"Viatchenko-Karpinski","sequence":"first","affiliation":[{"name":"1Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-3506","authenticated-orcid":false,"given":"Iryna A.","family":"Khasabova","sequence":"additional","affiliation":[{"name":"1Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Johns","sequence":"additional","affiliation":[{"name":"1Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Neal","sequence":"additional","affiliation":[{"name":"1Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Tang","sequence":"additional","affiliation":[{"name":"1Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, 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