{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:52:06Z","timestamp":1791597126985,"version":"4.3.4"},"reference-count":111,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Intraosseous lidocaine trigger point injection (LTPI) has been utilized for an extended period in the management of chronic vertebrogenic pain; yet, its molecular mechanisms and clinical efficacy require critical appraisal. This narrative review highlights the milestones of osteoreception and elucidates the molecular mechanisms driving intraosseous receptor irritation and its pivotal role in chronic pain development. Pathological vertebral bone remodeling triggers a receptor activator of nuclear factor-kappa B ligand\/osteoprotegerin (RANKL\/OPG) imbalance, accelerating hyperactive osteoclastogenesis. Enhanced osteoclastic vacuolar-type H+-ATPase (V-ATPase) expression drives microenvironment acidity and intraosseous hypertension, persistently stimulating acid-sensing ion channel 3 (ASIC3) and purinergic P2X2\/3 receptors on intraosseous afferents. Concurrently, upregulated nerve growth factor (NGF) binds to tropomyosin receptor kinase A (TrkA), driving peripheral sensitization via transient receptor potential vanilloid 1 (TRPV1) phosphorylation. The available clinical studies investigating intraosseous LTPI for vertebrogenic pain are scarce and heterogeneous, focusing primarily on low back pain, cervicalgia, and residual chronic pain after degenerative lumbar spinal stenosis decompression surgery. The reviewed data provide preliminary signals of potential benefit, observing a statistically significant analgesic effect of intraosseous LTPI within the studied cohorts. In two trials comparing it to intramuscular LTPI, one of which utilized a randomized controlled design, the intraosseous approach was reported to provide more pronounced short-term pain relief. However, these trials are limited by small sample sizes, heterogeneous designs, and a lack of active long-term safety monitoring. Nevertheless, although current data provide promising but still limited insights, future double-blinded, multicenter randomized controlled trials are required to comprehensively establish the clinical efficacy, safety profile, and prolonged effect of intraosseous LTPI in the treatment of vertebrogenic pain.<\/jats:p>","DOI":"10.3390\/ijms27198935","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:40:17Z","timestamp":1791596417000},"page":"8935","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intraosseous Lidocaine Trigger Point Injection for Vertebrogenic Pain: From Molecular Principles to Clinical Applications: A Narrative Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3643-982X","authenticated-orcid":false,"given":"Mustafa","family":"Al-Zamil","sequence":"first","affiliation":[{"name":"Department of Physiotherapy, Faculty of Continuing Medical Education, Peoples\u2019 Friendship University of Russia, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2840-837X","authenticated-orcid":false,"given":"Natalia A.","family":"Shnayder","sequence":"additional","affiliation":[{"name":"Institute of Personalized Psychiatry and Neurology, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology, 3 Bekhterev St., 192019 St. Petersburg, Russia"},{"name":"Shared Core Facilities \u201cMolecular and Cell Technologies\u201d, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizan Zheleznyak St., 660022 Krasnoyarsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8493-0058","authenticated-orcid":false,"given":"Marina M.","family":"Petrova","sequence":"additional","affiliation":[{"name":"Shared Core Facilities \u201cMolecular and Cell Technologies\u201d, V.F. 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