{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:02:43Z","timestamp":1789974163276,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":262,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-23323091"],"award-info":[{"award-number":["RS-2025-23323091"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pain Research and Management"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    The major bioactive constituent of\n                    <jats:italic>Syzygium aromaticum<\/jats:italic>\n                    (clove), eugenol, has been reported to possess analgesic and local anesthetic properties. However, direct evidence regarding the local anesthetic and antinociceptive effects of clove extract itself or its injectable formulations remains limited. Therefore, this study evaluated the neuroprotective, antinociceptive, and local anesthetic\u2010like effects of\n                    <jats:italic>S. aromaticum<\/jats:italic>\n                    pharmacopuncture (SAP) using\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    models, with comparative assessment against lidocaine. Primary dorsal root ganglion (DRG) neurons were exposed to H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced oxidative stress and treated with SAP. Cell viability, neurite outgrowth, intracellular reactive oxygen species (ROS), and pain\u2010related markers, including calcitonin gene\u2010related peptide (CGRP), isolectin B4 (IB4), and substance P, were evaluated.\n                    <jats:italic>In vivo<\/jats:italic>\n                    analgesic and anesthetic effects, including CFA\u2010induced inflammatory pain, were assessed using tail flick, von Frey, and hot plate tests in rat models. SAP significantly improved cell viability and promoted neurite outgrowth while attenuating oxidative stress\u2010induced cellular damage. Additionally, SAP markedly suppressed intracellular ROS levels and decreased the expression of pain\u2010related markers, including CGRP, IB4, and substance P.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , high\u2010dose SAP significantly increased tail flick latency, reaching cutoff levels comparable to those of 0.4% lidocaine. Furthermore, SAP attenuated mechanical hypersensitivity in the CFA\u2010induced inflammatory pain model and reduced microglial activation, inflammatory mediators (cyclooxygenase\u20102, interleukin\u20101\u03b2), and nociceptive marker expression in DRG and spinal cord tissues. These findings provide experimental evidence supporting the antinociceptive and local anesthetic\u2010like potential of SAP and highlight the involvement of oxidative stress modulation and nociceptive signaling in its pharmacological actions.\n                  <\/jats:p>","DOI":"10.1155\/prm\/5004039","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:26:52Z","timestamp":1789972012000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Analgesic and Local Anesthetic Effects of a Clove\u2010Derived Injectable Formulation via Modulation of Oxidative Stress and Nociceptive 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Jae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8121-2974","authenticated-orcid":false,"given":"Seung 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