{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:31:55Z","timestamp":1793493115087,"version":"4.5.0"},"reference-count":31,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Hyperalgesia is a condition marked by an abnormal increase in pain sensitivity, often occurring in response to tissue injury, inflammation, or prolonged exposure to certain medications. Inflammatory mediators, such as cytokines IL-1\u03b2, IL-6, and TNF-\u03b1, play a central role in this process, amplifying pain perception. Developing effective treatments that address the underlying mechanisms of hyperalgesia is an active field of research. Apis mellifera syriaca venom demonstrated potential immunomodulatory activity associated with cytokine release in vivo. Therefore, the aim of this study is to evaluate the effect of Apis mellifera syriaca bee venom (AmsBV) on pain sensitivity in a formalin-induced hyperalgesia mice model and to evaluate the potential role of cytokines associated with the nociception of pain. The hotplate test, used to measure pain latency, showed that hypersensitivity to pain was induced in formalin-injected male mice only, with no changes in females, suggesting a sex-based response to formalin. When applied, AmsBV reduced pain sensitivity in males, suggesting pain relief potential. At the molecular level, AmsBV was able to reduce pro-inflammatory interleukin IL-4 and cytokine IFN-\u03b3, emphasizing its immunomodulatory potential. Interestingly, the venom restored anti-inflammatory IL-10 levels that were significantly decreased in hyperalgesia males. Together, these findings highlight the therapeutic potential for AmsBV in managing inflammation and reducing pain, particularly hyperalgesia.<\/jats:p>","DOI":"10.3390\/toxins17010018","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T11:24:19Z","timestamp":1735730659000},"page":"18","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Influence of Apis mellifera syriaca Bee Venom on Nociception and Inflammatory Cytokine Profiles in Experimental Hyperalgesia"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1604-5253","authenticated-orcid":false,"given":"Mohamad","family":"Ayoub","sequence":"first","affiliation":[{"name":"Faculty of Sciences, University of Balamand, Al-Kourah, P.O. Box 100, Tripoli 1300, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Fayjaloun","sequence":"additional","affiliation":[{"name":"Department of Cell Culture, Laboratory of Applied Biotechnology (LBA3B), Azm Center for Research in Biotechnology and Its Applications, EDST, Lebanese University, Tripoli 1300, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4595-1104","authenticated-orcid":false,"given":"Rabih","family":"Roufayel","sequence":"additional","affiliation":[{"name":"College of Engineering and Technology, American University of the Middle East, Egaila 54200, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1967-1918","authenticated-orcid":false,"given":"Dany","family":"El Obeid","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture & Veterinary Sciences, Lebanese University, Dekwaneh, Beirut 2832, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6502-3110","authenticated-orcid":false,"given":"Ziad","family":"Fajloun","sequence":"additional","affiliation":[{"name":"Department of Cell Culture, Laboratory of Applied Biotechnology (LBA3B), Azm Center for Research in Biotechnology and Its Applications, EDST, Lebanese University, Tripoli 1300, Lebanon"},{"name":"Faculty of Sciences 3, Lebanese University, Michel Slayman Tripoli Campus, Ras Maska 1352, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0335-9882","authenticated-orcid":false,"given":"Mohamad","family":"Rima","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, Lebanese American University, Byblos P.O. Box 36, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Karam","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, University of Balamand, Al-Kourah, P.O. Box 100, Tripoli 1300, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.neuron.2006.09.021","article-title":"Mechanisms of neuropathic pain","volume":"52","author":"Campbell","year":"2006","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.36076\/ppj.2011\/14\/145","article-title":"A comprehensive review of opioid-induced hyperalgesia","volume":"14","author":"Lee","year":"2011","journal-title":"Pain Physician"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.cell.2009.09.028","article-title":"Cellular and molecular mechanisms of pain","volume":"139","author":"Basbaum","year":"2009","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"411","DOI":"10.2217\/pmt-2020-0015","article-title":"Botulinum toxin injections for shoulder and upper limb pain: A narrative review","volume":"10","author":"Chang","year":"2020","journal-title":"Pain Manag."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nri3621","article-title":"Pathological pain and the neuroimmune interface","volume":"14","author":"Grace","year":"2014","journal-title":"Nat. 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