{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:58:03Z","timestamp":1787579883242,"version":"build-2736575974"},"reference-count":92,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,7]],"date-time":"2024-09-07T00:00:00Z","timestamp":1725667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["2020R1A5A2019413"],"award-info":[{"award-number":["2020R1A5A2019413"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>To evaluate the efficacy of human placenta hydrolysate (HPH) in a mice model of CFA-induced inflammatory pain. TNF-\u03b1, IL-1\u03b2, and IL-6 are key pro-inflammatory cytokine factors for relieving inflammatory pain. Therefore, this study investigates whether HPH suppresses CFA-induced pain and attenuates the inflammatory process by regulating cytokines. In addition, the relationship between neuropathic pain and HPH was established by staining GFAP and Iba-1 in mice spinal cord tissues. This study was conducted for a total of day 28, and inflammatory pain was induced in mice by injecting CFA into the right paw at day 0 and day 14, respectively. 100 \u03bcL of 20% glucose and polydeoxyribonucleotide (PDRN) and 100, 200, and 300 \u03bcL of HPH were administered intraperitoneally twice a week. In the CFA-induced group, cold and mechanical allodynia and pro-inflammatory cytokine factors in the spinal cord and plantar tissue were significantly increased. The five groups of drugs evenly reduced pain and gene expression of inflammatory factors, and particularly excellent effects were confirmed in the HPH 200 and 300 groups. Meanwhile, the expression of GFAP and Iba-1 in the spinal cord was increased by CFA administration but decreased by HPH administration, which was confirmed to suppress damage to peripheral ganglia. The present study suggests that HPH attenuates CFA-induced inflammatory pain through inhibition of pro-inflammatory cytokine factors and protection of peripheral nerves.<\/jats:p>","DOI":"10.3390\/ph17091179","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T03:04:18Z","timestamp":1725851058000},"page":"1179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Analgesic Effect of Human Placenta Hydrolysate on CFA-Induced Inflammatory Pain in Mice"],"prefix":"10.3390","volume":"17","author":[{"given":"Keun-Tae","family":"Park","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02453, Republic of Korea"},{"name":"Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02453, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejoon","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02453, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Hyun","family":"Jeon","sequence":"additional","affiliation":[{"name":"Research and Development Center, Green Cross Wellbeing Corporation, Yongin 16950, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeongsoo","family":"Jeong","sequence":"additional","affiliation":[{"name":"Research and Development Center, Green Cross Wellbeing Corporation, Yongin 16950, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minju","family":"Im","sequence":"additional","affiliation":[{"name":"Research and Development Center, Green Cross Wellbeing Corporation, Yongin 16950, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Research and Development Center, Green Cross Wellbeing Corporation, Yongin 16950, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Pil","family":"Jung","sequence":"additional","affiliation":[{"name":"Nuke Medical Society of Pain Research, Daejeon 35002, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoe Chang","family":"Jung","sequence":"additional","affiliation":[{"name":"Nuke Medical Society of Pain Research, Daejeon 35002, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae hun","family":"Lee","sequence":"additional","affiliation":[{"name":"Nuke Medical Society of Pain Research, Daejeon 35002, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-4524","authenticated-orcid":false,"given":"Woojin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02453, Republic of Korea"},{"name":"Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02453, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nrd2757","article-title":"Transient receptor potential channels: Targeting pain at the source","volume":"8","author":"Patapoutian","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/S0006-8993(01)02743-3","article-title":"Anti-TNF-neutralizing antibodies reduce pain-related behavior in two different mouse models of painful mononeuropathy","volume":"913","author":"Sommer","year":"2001","journal-title":"Brain Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jep.2017.03.036","article-title":"Antinociceptive and anti-inflammatory effects of the methanolic stem bark extract of Antrocaryon klaineanum Pierre (Anacardiaceae) in mice and rat","volume":"203","author":"Fongang","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1111\/j.1460-9568.2005.04470.x","article-title":"An initial investigation of spinal mechanisms underlying pain enhancement induced by fractalkine, a neuronally released chemokine","volume":"22","author":"Milligan","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1111\/j.1476-5381.1992.tb14503.x","article-title":"The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia","volume":"107","author":"Cunha","year":"1992","journal-title":"Br. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/334698a0","article-title":"Interleukin-1 beta as a potent hyperalgesic agent antagonized by a tripeptide analogue","volume":"334","author":"Ferreira","year":"1988","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.pharmthera.2006.04.001","article-title":"Hypernociceptive role of cytokines and chemokines: Targets for analgesic drug development?","volume":"112","author":"Verri","year":"2006","journal-title":"Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.neulet.2008.03.050","article-title":"Cytokine regulation in animal models of neuropathic pain and in human diseases","volume":"437","author":"Sommer","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3727\/000000007783992807","article-title":"Cytokine-induced pain: Basic science and clinical implications","volume":"9","author":"Sommer","year":"2007","journal-title":"Rev. Analg."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Liu, L.R., Liu, J.C., Bao, J.S., Bai, Q.Q., and Wang, G.Q. (2020). Interaction of Microglia and Astrocytes in the Neurovascular Unit. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01024"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.7150\/ijbs.4679","article-title":"Interleukin-6, a major cytokine in the central nervous system","volume":"8","author":"Erta","year":"2012","journal-title":"Int. J. Biol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gajtk\u00f3, A., Bakk, E., Heged\u0171s, K., Ducza, L., and Holl\u00f3, K. (2020). IL-1\u03b2 Induced Cytokine Expression by Spinal Astrocytes Can Play a Role in the Maintenance of Chronic Inflammatory Pain. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.543331"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1097\/ALN.0000000000002130","article-title":"Neuroinflammation and central sensitization in chronic and widespread pain","volume":"129","author":"Ji","year":"2018","journal-title":"Anesthesiology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1007\/s13311-020-00905-7","article-title":"Central nervous system targets: Glial cell mechanisms in chronic pain","volume":"17","author":"Donnelly","year":"2020","journal-title":"Neurotherapeutics"},{"key":"ref_15","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. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nrd.2017.87","article-title":"Breaking barriers to novel analgesic drug development","volume":"16","author":"Yekkirala","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/0027-5107(82)90278-0","article-title":"Antimutagenic action of mammalian placental extracts on mutations induced in Escherichia coli by UV radiation, \u03b3-rays and N-methyl-N\u2032-nitro-N-nitrosoguanidine","volume":"95","author":"Mochizuki","year":"1982","journal-title":"Mutat. Res.\/Fundam. Mol. Mech. Mutagen."},{"key":"ref_18","first-page":"361","article-title":"Anti-inflammatory effect of human placental extract: A biochemical mechanistic approach","volume":"14","author":"Banerjee","year":"1992","journal-title":"Riv. Eur. Sci. Med. Farmacol. = Eur. Rev. Med. Pharmacol. Sci. = Rev. Eur. Sci. Med. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1248\/bpb.21.44","article-title":"Human placental extract stimulates liver regeneration in rats","volume":"21","author":"Liu","year":"1998","journal-title":"Biol. Pharm. Bull."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.intimp.2011.02.012","article-title":"Placenta extract promote liver regeneration in CCl4-injured liver rat model","volume":"11","author":"Jung","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1080\/14786419.2010.489050","article-title":"Anti-inflammatory and analgesic effects of human placenta extract","volume":"25","author":"Lee","year":"2011","journal-title":"Nat. Prod. Res."},{"key":"ref_22","first-page":"187","article-title":"Anti-inflammatory and anti-platelet aggregation activity of human placental extract","volume":"24","author":"Sur","year":"2003","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.3892\/ijmm.2015.2316","article-title":"Human placental extract exerts hair growth-promoting effects through the GSK-3\u03b2 signaling pathway in human dermal papilla cells","volume":"36","author":"Kwon","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1210\/jcem-55-2-384","article-title":"Corticotropin-releasing factor-like activity in human placental extracts","volume":"55","author":"Shibasaki","year":"1982","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jams.2014.03.004","article-title":"Complex regional pain syndrome type 1 relieved by acupuncture point injections with placental extract","volume":"7","author":"Cho","year":"2014","journal-title":"J. Acupunct. Meridian Stud."},{"key":"ref_26","unstructured":"Cho, T., and Park, K. (2016). Use of acupuncture point injection with placental extract for treatment of complex regional pain syndrome. J. Pain Relief, 5."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S2095-4964(17)60316-9","article-title":"Therapeutic effect of acupuncture point injection with placental extract in knee osteoarthritis","volume":"15","author":"Park","year":"2017","journal-title":"J. Integr. Med."},{"key":"ref_28","first-page":"227","article-title":"Sur l\u2019augmentation anormale de l\u2019antitoxine chez les chevaux producteurs de serum antidiphterique","volume":"101","author":"Ramon","year":"1925","journal-title":"Bull. Soc. Centr. Med. Vet."},{"key":"ref_29","first-page":"1","article-title":"Procedes pour acroitre la production des antitoxins","volume":"40","author":"Ramon","year":"1926","journal-title":"Ann. Inst. Pasteur."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"399","DOI":"10.4049\/jimmunol.36.5.399","article-title":"Sensitization and antibody formation in monkeys injected with tubercle bacilli in paraffin oil","volume":"36","author":"Casals","year":"1939","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/0161-5890(91)90074-T","article-title":"Immunological adjuvants: Desirable properties and side-effects","volume":"28","author":"Allison","year":"1991","journal-title":"Mol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1089\/wound.2019.1031","article-title":"Polydeoxyribonucleotide Regulation of Inflammation","volume":"9","author":"Colangelo","year":"2020","journal-title":"Adv. Wound Care"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e12794","DOI":"10.1097\/MD.0000000000012794","article-title":"The effect of polydeoxyribonucleotide on the treatment of radiating leg pain due to cystic mass lesion in inner aspect of right sciatic foramen: A CARE compliant case report","volume":"97","author":"Lee","year":"2018","journal-title":"Medicine"},{"key":"ref_34","first-page":"107","article-title":"Subcutaneous prolotherapy for achilles tendinopathy: The best solution?","volume":"12","author":"Lyftogt","year":"2007","journal-title":"Australas. Musculoskelet. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1093\/rheumatology\/keaa361","article-title":"Long-term outcome after perineural injection with 5% dextrose for carpal tunnel syndrome: A retrospective follow-up study","volume":"60","author":"Li","year":"2021","journal-title":"Rheumatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/prd.12034","article-title":"Natural resolution of inflammation","volume":"63","author":"Freire","year":"2013","journal-title":"Periodontology 2000"},{"key":"ref_37","unstructured":"Chandrasoma, P., and Taylor, C.R. (1998). Chapter 3. The Acute Inflammatory Response. Concise Pathology, The McGraw-Hill Companies."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.tins.2003.09.017","article-title":"Central sensitization and LTP: Do pain and memory share similar mechanisms?","volume":"26","author":"Ji","year":"2003","journal-title":"Trends Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/nn1992","article-title":"The neuropathic pain triad: Neurons, immune cells and glia","volume":"10","author":"Scholz","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.2174\/1381612823666170210150147","article-title":"PI3K\/Akt pathway: A potential therapeutic target for chronic pain","volume":"23","author":"Chen","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1007\/s11064-016-1827-y","article-title":"CX3CR1-mediated Akt1 activation contributes to the paclitaxel-induced painful peripheral neuropathy in rats","volume":"41","author":"Li","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1248\/bpb.b19-00349","article-title":"Effects of human placenta extract (Laennec) on ligament healing in a rodent model","volume":"42","author":"Shin","year":"2019","journal-title":"Biol. Pharm. Bull."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/S0002-9378(15)30252-0","article-title":"Composition of the Human Placenta: I. Proximate Composition","volume":"52","author":"Pratt","year":"1946","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.pain.2010.09.030","article-title":"Central sensitization: Implications for the diagnosis and treatment of pain","volume":"152","author":"Woolf","year":"2011","journal-title":"Pain"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.jpain.2009.06.012","article-title":"Central sensitization: A generator of pain hypersensitivity by central neural plasticity","volume":"10","author":"Latremoliere","year":"2009","journal-title":"J. Pain"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Squadrito, F., Bitto, A., Irrera, N., Pizzino, G., Pallio, G., Minutoli, L., and Altavilla, D. (2017). Pharmacological activity and clinical use of PDRN. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00224"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Jeong, W., Yang, C.E., Roh, T.S., Kim, J.H., Lee, J.H., and Lee, W.J. (2017). Scar prevention and enhanced wound healing induced by polydeoxyribonucleotide in a rat incisional wound-healing model. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081698"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"181","DOI":"10.5999\/aps.2013.40.3.181","article-title":"The effects of polydeoxyribonucleotide on the survival of random pattern skin flaps in rats","volume":"40","author":"Chung","year":"2013","journal-title":"Arch. Plast. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"630","DOI":"10.5535\/arm.2018.42.4.630","article-title":"The effect of polydeoxyribonucleotide on chronic non-healing wound of an amputee: A case report","volume":"42","author":"Shin","year":"2018","journal-title":"Ann. Rehabil. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1016\/S0024-3205(03)00547-2","article-title":"Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: A new proposal for bone tissue repair","volume":"73","author":"Guizzardi","year":"2003","journal-title":"Life Sci."},{"key":"ref_51","first-page":"400","article-title":"Anti-inflammatory effect of polydeoxyribonucleotide on zoledronic acid-pretreated and lipopolysaccharide-stimulated RAW 264.7 cells","volume":"16","author":"Han","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s10753-017-0722-2","article-title":"Anti-inflammatory effect of DNA polymeric molecules in a cell model of osteoarthritis","volume":"41","author":"Baek","year":"2018","journal-title":"Inflammation"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lee, W.J., Jo, S.Y., Lee, M.H., Won, C.H., Lee, M.W., Choi, J.H., and Chang, S.E. (2016). The effect of MCP-1\/CCR2 on the proliferation and senescence of epidermal constituent cells in solar lentigo. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060948"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Edgar, S., Hopley, B., Genovese, L., Sibilla, S., Laight, D., and Shute, J. (2018). Effects of collagen-derived bioactive peptides and natural antioxidant compounds on proliferation and matrix protein synthesis by cultured normal human dermal fibroblasts. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-28492-w"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/s41392-021-00828-5","article-title":"Targeting PI3K\/Akt signal transduction for cancer therapy","volume":"6","author":"He","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"16027","DOI":"10.1073\/pnas.0602488103","article-title":"A role for adrenomedullin as a pain-related peptide in the rat","volume":"103","author":"Ma","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Buel, G.R., Dang, H.Q., Asara, J.M., Blenis, J., and Mutvei, A.P. (2022). Prolonged deprivation of arginine or leucine induces PI3K\/Akt-dependent reactivation of mTORC1. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.102030"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5149","DOI":"10.1021\/acs.jafc.8b01111","article-title":"Leucine Affects \u03b1-Amylase Synthesis through PI3K\/Akt-mTOR Signaling Pathways in Pancreatic Acinar Cells of Dairy Calves","volume":"66","author":"Guo","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"018","DOI":"10.7324\/JAPS.2022.120803","article-title":"Porcine placenta extract induced Akt, ERK, and JNK signaling to heighten the osteogenic activity of human osteoblasts","volume":"12","author":"Songjang","year":"2022","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Aioi, A., Muromoto, R., Kashiwakura, J.-i., Mogami, S., Nishikawa, M., Ogawa, S., and Matsuda, T. (2022). Porcine placenta extract upregulates ceramide synthase 3 expression via the PPAR\u03b4\/ILK\/Akt\/mTOR\/STAT3 pathway. bioRxiv.","DOI":"10.1101\/2022.05.23.493164"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0014-2999(01)01311-5","article-title":"Involvement of chemokines in pain","volume":"429","author":"Boddeke","year":"2001","journal-title":"Eur. J. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S1569-2558(03)31042-2","article-title":"The role of astrocytes and microglia in persistent pain","volume":"31","author":"Raghavendra","year":"2003","journal-title":"Adv. Mol. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/j.1460-9568.2004.03514.x","article-title":"Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS","volume":"20","author":"Raghavendra","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.yexcr.2018.05.012","article-title":"Glycyrrhizin ameliorates inflammatory pain by inhibiting microglial activation-mediated inflammatory response via blockage of the HMGB1-TLR4-NF-kB pathway","volume":"369","author":"Sun","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.it.2017.12.003","article-title":"Immune Cytokines and Their Receptors in Inflammatory Pain","volume":"39","author":"Cook","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1124\/pr.57.4.4","article-title":"International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels","volume":"57","author":"Catterall","year":"2005","journal-title":"Pharmacol. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.1523\/JNEUROSCI.2061-14.2015","article-title":"Selective activation of microglia facilitates synaptic strength","volume":"35","author":"Clark","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1126\/science.aah5715","article-title":"Gliogenic LTP spreads widely in nociceptive pathways","volume":"354","author":"Gassner","year":"2016","journal-title":"Science"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6540","DOI":"10.1523\/JNEUROSCI.5087-12.2013","article-title":"Induction of thermal hyperalgesia and synaptic long-term potentiation in the spinal cord lamina I by TNF-\u03b1 and IL-1\u03b2 is mediated by glial cells","volume":"33","author":"Wunderbaldinger","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1097\/00000542-200607000-00022","article-title":"Effects of Bupivacaine and Tetrodotoxin on Carrageenan-induced Hind Paw Inflammation in Rats (Part 1) Hyperalgesia, Edema, and Systemic Cytokines","volume":"105","author":"Beloeil","year":"2006","journal-title":"J. Am. Soc. Anesthesiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0006-8993(99)01326-8","article-title":"Acute peripheral inflammation induces moderate glial activation and spinal IL-1\u03b2 expression that correlates with pain behavior in the rat","volume":"829","author":"Sweitzer","year":"1999","journal-title":"Brain Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1002\/art.23866","article-title":"Spinal interleukin-1\u03b2 in a mouse model of arthritis and joint pain","volume":"58","author":"Fiorentino","year":"2008","journal-title":"Arthritis Rheum. Off. J. Am. Coll. Rheumatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"7251","DOI":"10.1073\/pnas.84.20.7251","article-title":"Interferon beta 2\/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells","volume":"84","author":"Gauldie","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1073\/pnas.91.1.43","article-title":"Neuropoietic cytokines and activin A differentially regulate the phenotype of cultured sympathetic neurons","volume":"91","author":"Fann","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/0306-4522(91)90132-8","article-title":"Interleukin-6 improves the survival of mesencephalic catecholaminergic and septal cholinergic neurons from postnatal, two-week-old rats in cultures","volume":"40","author":"Hama","year":"1991","journal-title":"Neuroscience"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1111\/j.1460-9568.1995.tb01042.x","article-title":"IL-6 expression in neurons of transgenic mice causes reactive astrocytosis and increase in ramified microglial cells but no neuronal damage","volume":"7","author":"Fattori","year":"1995","journal-title":"Eur. J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1159\/000112109","article-title":"Reactive gliosis as a consequence of interleukin-6 expression in the brain: Studies in transgenic mice","volume":"16","author":"Chiang","year":"1994","journal-title":"Dev. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"10061","DOI":"10.1073\/pnas.90.21.10061","article-title":"Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6","volume":"90","author":"Campbell","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"19448","DOI":"10.1016\/S0021-9258(18)41796-6","article-title":"Differentiation factors, including nerve growth factor, fibroblast growth factor, and interleukin-6, induce an accumulation of an active Ras. GTP complex in rat pheochromocytoma PC12 cells","volume":"267","author":"Nakafuku","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0006-8993(95)00691-I","article-title":"Intracerebroventricular injection of interleukin-6 induces thermal hyperalgesia in rats","volume":"692","author":"Oka","year":"1995","journal-title":"Brain Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1089\/jir.1996.16.695","article-title":"Interleukin-6-mediated hyperalgesia\/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model","volume":"16","author":"DeLEO","year":"1996","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/0166-2236(96)10049-7","article-title":"Microglia: A sensor for pathological events in the CNS","volume":"19","author":"Kreutzberg","year":"1996","journal-title":"Trends Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/00019052-200108000-00009","article-title":"The role of glial cells in Parkinson\u2019s disease","volume":"14","author":"Vila","year":"2001","journal-title":"Curr. Opin. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/nrd1251","article-title":"Glia: A novel drug discovery target for clinical pain","volume":"2","author":"Watkins","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s12974-020-01891-5","article-title":"Microglia induce the transformation of A1\/A2 reactive astrocytes via the CXCR7\/PI3K\/Akt pathway in chronic post-surgical pain","volume":"17","author":"Li","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/32897","article-title":"Primary afferent tachykinins are required to experience moderate to intense pain","volume":"392","author":"Cao","year":"1998","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.cell.2018.02.057","article-title":"A neural circuit for the suppression of pain by a competing need state","volume":"173","author":"Alhadeff","year":"2018","journal-title":"Cell"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Ji, H., Ko, S.-G., and Kim, W. (2021). Ji017 attenuates oxaliplatin-induced cold allodynia via spinal trpv1 and astrocytes inhibition in mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168811"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Min, D., Lee, D., and Kim, W. (2021). Zingiber officinale roscoe rhizomes attenuate oxaliplatin-induced neuropathic pain in mice. Molecules, 26.","DOI":"10.3390\/molecules26030548"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev.pa.20.040180.002301","article-title":"Efficient analysis of experimental observations","volume":"20","author":"Dixon","year":"1980","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0165-0270(94)90144-9","article-title":"Quantitative assessment of tactile allodynia in the rat paw","volume":"53","author":"Chaplan","year":"1994","journal-title":"J. Neurosci. Methods"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Hussein, S.Z., Mohd Yusoff, K., Makpol, S., and Mohd Yusof, Y.A. (2013). Gelam honey attenuates carrageenan-induced rat paw inflammation via NF-\u03baB pathway. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072365"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/9\/1179\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:50:12Z","timestamp":1760111412000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/9\/1179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,7]]},"references-count":92,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ph17091179"],"URL":"https:\/\/doi.org\/10.3390\/ph17091179","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,7]]}}}