APITOXIN IN THE TREATMENT OF JOINT, MUSCULOSKELETAL INFLAMMATION, FIBROMYALGIA AND CHRONIC PAIN: A SYSTEMATIC LITERATURE REVIEW (2015–2025)
DOI:
https://doi.org/10.56238/revgeov17n5-144Keywords:
Apitoxin, Bee Venom, Anti-Inflammatory, Rheumatoid Arthritis, Chronic PainAbstract
Objective: To consolidate scientific evidence (2015–2025) on the therapeutic use of apitoxin (Apis mellifera venom) in joint and musculoskeletal inflammatory conditions, fibromyalgia, and chronic pain. Methodology: Systematic narrative review searching PubMed, PMC, Scopus and Web of Science with descriptors: bee venom, apitoxin, rheumatoid arthritis, osteoarthritis, fibromyalgia, chronic pain, musculoskeletal. Included RCTs, systematic reviews and meta-analyses published between 2015 and 2025. Results: Apitoxin demonstrates anti-inflammatory and analgesic efficacy through NF-κB pathway inhibition and suppression of TNF-α, IL-1β, IL-6 and COX-2. A meta-analysis (Sung et al., 2025) confirmed significant pain reduction (MD: –16.93; 95% CI: –26.35 to –7.51; p < 0.0001). Strong evidence for rheumatoid arthritis and osteoarthritis; promising data for fibromyalgia and chronic pain.
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References
AUFSCHNAITER, A. et al. Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities. Toxins, v. 12, n. 2, p. 66, 2020. DOI: 10.3390/toxins12020066.
BEST BEES. All About Bee Venom: Therapeutic Properties & 7 Uses in Medicine. Disponível em: https://bestbees.com/bee-venom/. Acesso em: fev. 2026.
BHARDWAJ, V.; THAKUR, N.; KUMARI, P. Harnessing bee venom for inflammatory diseases management: from traditional medicine to nanotechnology. Naunyn-Schmiedeberg's Archives of Pharmacology, v. 398, n. 8, p. 9797–9815, 2025. DOI: 10.1007/s00210-025-03991-6.
BIJAK, M. et al. Therapeutic Potential and Mechanisms of Bee Venom Therapy: A Comprehensive Review of Apitoxin Applications and Safety Enhancement Strategies. Pharmaceuticals, v. 17, n. 9, p. 1211, 2024. DOI: 10.3390/ph17091211. PMID: 39338374.
CHERNIACK, E. P.; GOVORUSHKO, S. To bee or not to bee: the potential efficacy and safety of bee venom acupuncture in humans. Toxicon, v. 154, p. 74–78, 2018.
CHOI, Y. et al. Bee venom acupuncture alleviates experimental delayed onset muscle soreness. Evidence-Based Complementary and Alternative Medicine, 2016.
CONRAD, V. J. et al. Efficacy and Safety of Honey Bee Venom (Apis mellifera) Dermal Injections to Treat Osteoarthritis Knee Pain and Physical Disability: A Randomized Controlled Trial. Journal of Alternative and Complementary Medicine, v. 25, n. 10, p. 845–855, 2019. DOI: 10.1089/acm.2019.0121.
CUNHA LIMA, J. R. Patente BR 10 2021 019498 1 – Apitoxina 30 Bioactive®. INPI, Brasil, 2021.
CUNHA LIMA, J. R. Modelo de Utilidade BR 20 2026 008167 1 – ApisPen 30 Bioactive®. INPI, Brasil, 2026.
CUNHA LIMA, J. R. Nanopartículas de ZnO funcionalizadas com apitoxina: desenvolvimento e caracterização. Tese de Doutorado em andamento. PPGBiotec/UFDPar, 2025.
EBSCO RESEARCH. Bee Venom Therapy. Health and Medicine. Research Starters. EBSCO Information Services, 2024.
IM, E. J. et al. Anti-Inflammatory Activity of Bee Venom in Bv2 Microglial Cells: Mediation of Myd88-Dependent Nf-Κb Signaling Pathway. Evidence-Based Complementary and Alternative Medicine, v. 2016, p. 3704764, 2016. DOI: 10.1155/2016/3704764.
KARPIŃSKI, T. M. et al. Myorelaxant Effect of Bee Venom Topical Skin Application in Patients with RDC/TMD Ia and RDC/TMD Ib: A Randomized, Double Blinded Study. Evidence-Based Complementary and Alternative Medicine, 2014. PMC4094729.
KARPIŃSKI, T. M. et al. Therapeutic Bioactivity Exerted by the Apis mellifera Bee Venom and Its Major Protein Melittin: A Scoping Review. PMC12525935, 2024.
KWON, Y. B. et al. The Anti-Inflammatory Effect of Bee Venom Stimulation in a Mouse Air Pouch Model Is Mediated by Adrenal Medullary Activity. Journal of Neuroendocrinology, v. 15, p. 93–96, 2003.
LEE, G. et al. Clinical Effectiveness and Adverse Events of Bee Venom Therapy: A Systematic Review of Randomized Controlled Trials. Toxins, v. 12, n. 9, p. 558, 2020. PMC7551670. DOI: 10.3390/toxins12090558.
LIU, X. D.; TONG, F. Clinical randomized study of bee-sting therapy for rheumatoid arthritis. Zhen Ci Yan Jiu, v. 33, n. 3, p. 197–200, 2008.
MELO, W. F. et al. Os efeitos benéficos da apitoxina no tratamento das doenças autoimunes: uma revisão bibliográfica. Caderno Verde de Agroecologia e Desenvolvimento Sustentável, v. 13, n. 2, p. 44, 2024.
MOHAMED, E. A.; EWIDA, M. M. Efficacy of bee venom phonophoresis in treatment of chronic pelvic inflammatory diseases. International Journal of PharmTech Research, v. 9, p. 66–71, 2016.
NIU, J. et al. Melittin Treats Periprosthetic Osteolysis in a Rat Model by Inhibiting the NF-kB Pathway and Regulating the Ratio of RANKL/Osteoprotegerin. Journal of Arthroplasty, v. 39, p. 1845–1855, 2024. DOI: 10.1016/j.arth.2024.01.062.
PAREEK, A. et al. Melittin as a therapeutic agent for rheumatoid arthritis: mechanistic insights, advanced delivery systems, and future perspectives. Frontiers in Immunology, v. 15, p. 1510693, 2024. DOI: 10.3389/fimmu.2024.1510693.
PARK, J. H. et al. Therapeutic Potential of Bee and Wasp Venom in Anti-Arthritic Treatment: A Review. Toxins, v. 16, n. 11, p. 452, 2024. PMC11598298. DOI: 10.3390/toxins16110452.
RUVOLO-TAKASUSUKI, M. C. C.; DE SOUZA, P. M. Apitoxina: Utilização do veneno da abelha Apis mellifera. PUBVET, v. 13, p. 153, 2019.
SEO, B.-K. et al. Efficacy of Bee Venom Acupuncture for Chronic Low Back Pain: A Randomized, Double-Blinded, Sham-Controlled Trial. Toxins, v. 9, n. 11, p. 361, 2017. DOI: 10.3390/toxins9110361.
SHIN, B.-C. et al. Bee venom acupuncture for chronic low back pain: A randomised, sham-controlled, triple-blind clinical trial. European Journal of Integrative Medicine, v. 4, n. 4, p. E271–E280, 2012. DOI: 10.1016/j.eujim.2012.02.005.
SRIWIDODO, S. et al. Bee venom in pharmacology: mechanistic insights from pro-inflammatory trigger to anti-inflammatory therapeutic agent. Biomedicine & Pharmacotherapy, v. 192, p. 118636, 2025. DOI: 10.1016/j.biopha.2025.118636.
SUNG, S. H. et al. Bee venom acupuncture for musculoskeletal pain conditions: an updated systematic review and meta-analysis. BMC Complementary Medicine and Therapies, v. 25, p. 161, 2025. DOI: 10.1186/s12906-025-04891-1.
TEKEOĞLU, İ. et al. Investigation of anti-inflammatory effects of bee venom in experimentally induced adjuvant arthritis. Experimental and Therapeutic Medicine, 2020. PMC7667938. DOI: 10.3892/etm.2020.9240.
YANG, L. et al. Exploring Potential Network Pharmacology-and Molecular Docking-Based Mechanism of Melittin in Treating Rheumatoid Arthritis. Medicine, v. 102, p. e34728, 2023. DOI: 10.1097/MD.0000000000034728.
YOUSEFPOOR, Y. et al. Anti-Rheumatic Activity of Topical Nanoemulsion Containing Bee Venom in Rats. European Journal of Pharmaceutical Biopharmaceutics, v. 172, p. 168–176, 2022. DOI: 10.1016/j.ejpb.2022.02.005.
ZAKARIA, Z. A. et al. Systemic bee venom exerts anti-arthritic and anti-inflammatory properties in a rat model of arthritis. Experimental and Therapeutic Medicine, 2020. PMC7403832.
