{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:08:05Z","timestamp":1791479285024,"version":"4.3.4"},"reference-count":83,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"cycle XXXVIII of the Doctorate in Pharmacological Biomolecular Sciences, Experimental and Clinical, University of Milan, Milan, Italy"},{"name":"Fondazione Umberto Veronesi ETS, Milan, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Osteoarthritis (OA) is the most prevalent joint disease associated with chronic pain. OA pain is often accompanied by mood disorders. We addressed the role of the Prokineticin (PK) system in pain and mood alterations in a mice OA model induced with monosodium iodoacetate (MIA). The effect of a PK antagonist (PC1) was compared to that of diclofenac. C57BL\/6J male mice injected with MIA in the knee joint were characterized by allodynia, motor deficits, and fatigue. Twenty-eight days after MIA, in the knee joint, we measured high mRNA of PK2 and its receptor PKR1, pro-inflammatory cytokines, and MMP13. At the same time, in the sciatic nerve and spinal cord, we found increased levels of PK2, PKR1, IL-1\u03b2, and IL-6. These changes were in the presence of high GFAP and CD11b mRNA in the sciatic nerve and GFAP in the spinal cord. OA mice were also characterized by anxiety, depression, and neuroinflammation in the prefrontal cortex and hippocampus. In both stations, we found increased pro-inflammatory cytokines. In addition, PK upregulation and reactive astrogliosis in the hippocampus and microglia reactivity in the prefrontal cortex were detected. PC1 reduced joint inflammation and neuroinflammation in PNS and CNS and counteracted OA pain and emotional disturbances.<\/jats:p>","DOI":"10.3390\/cells12182255","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T04:38:48Z","timestamp":1694493528000},"page":"2255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Prokineticin System Is a Pharmacological Target to Counteract Pain and Its Comorbid Mood Alterations in an Osteoarthritis Murine Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5163-7480","authenticated-orcid":false,"given":"Giulia","family":"Galimberti","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4097-3195","authenticated-orcid":false,"given":"Giada","family":"Amodeo","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0995-8947","authenticated-orcid":false,"given":"Giulia","family":"Magni","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5328-1999","authenticated-orcid":false,"given":"Benedetta","family":"Riboldi","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4437-6096","authenticated-orcid":false,"given":"Gianfranco","family":"Balboni","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2438-725X","authenticated-orcid":false,"given":"Valentina","family":"Onnis","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1663-4211","authenticated-orcid":false,"given":"Stefania","family":"Ceruti","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-511X","authenticated-orcid":false,"given":"Paola","family":"Sacerdote","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Franchi","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/j.joca.2013.06.013","article-title":"Osteoarthritis pain mechanisms: Basic studies in animal models","volume":"21","author":"Zhang","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3389\/fnmol.2017.00349","article-title":"Mechanisms of Osteoarthritic Pain. Studies in Humans and Experimental Models","volume":"10","author":"Eitner","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_3","first-page":"79","article-title":"The role of centralised pain in osteoarthritis","volume":"35","author":"Clauw","year":"2017","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nrrheum.2016.136","article-title":"Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis","volume":"12","author":"Robinson","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Guida, F., Rocco, M., Luongo, L., Persiani, P., Vulpiani, M.C., Nusca, S.M., Maione, S., and Coluzzi, F. (2022). Targeting Neuroinflammation in Osteoarthritis with Intra-Articular Adelmidrol. Biomolecules, 12.","DOI":"10.3390\/biom12101453"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41584-022-00749-9","article-title":"Synovial inflammation in osteoarthritis progression","volume":"18","author":"Coras","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00221-009-1782-9","article-title":"Joint pain","volume":"196","author":"Schaible","year":"2009","journal-title":"Exp. Brain Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13075-017-1229-9","article-title":"Synovitis in osteoarthritis: Current understanding with therapeutic implications","volume":"19","author":"Mathiessen","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.tvjl.2007.08.013","article-title":"The contribution of the synovium, synovial derived inflammatory cytokines and neuropeptides to the pathogenesis of osteoarthritis","volume":"179","author":"Sutton","year":"2009","journal-title":"Vet. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1007\/s10067-010-1547-7","article-title":"Prevalence of anxiety and depression in osteoarthritis: Use of the Hospital Anxiety and Depression Scale as a screening tool","volume":"29","author":"Axford","year":"2010","journal-title":"Clin. Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.semarthrit.2008.11.005","article-title":"The interface of pain and mood disturbances in the rheumatic diseases","volume":"40","author":"Goldenberg","year":"2010","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.2147\/OARRR.S93516","article-title":"Anxiety and depression in patients with osteoarthritis: Impact and management challenges","volume":"8","author":"Sharma","year":"2016","journal-title":"Open Access Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.pneurobio.2011.01.002","article-title":"The effect of pain on cognitive function: A review of clinical and preclinical research","volume":"93","author":"Moriarty","year":"2011","journal-title":"Prog. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1097\/SPC.0000000000000054","article-title":"Cognition and pain","volume":"8","author":"Moriarty","year":"2014","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1097\/j.pain.0000000000000260","article-title":"Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain","volume":"156","author":"Bura","year":"2015","journal-title":"Pain"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1111\/bph.14794","article-title":"Sigma-1 receptor modulates neuroinflammation associated with mechanical hypersensitivity and opioid tolerance in a mouse model of osteoarthritis pain","volume":"176","author":"Kummer","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"468","DOI":"10.3389\/fphar.2019.00468","article-title":"Blockade of the Sigma-1 Receptor Relieves Cognitive and Emotional Impairments Associated to Chronic Osteoarthritis Pain","volume":"10","author":"Zamanillo","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Batall\u00e9, G., Cabarga, L., and Pol, O. (2019). The Inhibitory Effects of Slow-Releasing Hydrogen Sulfide Donors in the Mechanical Allodynia, Grip Strength Deficits, and Depressive-Like Behaviors Associated with Chronic Osteoarthritis Pain. Antioxidants, 9.","DOI":"10.3390\/antiox9010031"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Batall\u00e9, G., Bai, X., Pouso-V\u00e1zquez, E., Roch, G., Rodr\u00edguez, L., and Pol, O. (2021). The Recovery of Cognitive and Affective Deficiencies Linked with Chronic Osteoarthritis Pain and Implicated Pathways by Slow-Releasing Hydrogen Sulfide Treatment. Antioxidants, 10.","DOI":"10.3390\/antiox10101632"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.neubiorev.2020.04.029","article-title":"Pain in neuropsychiatry: Insights from animal models","volume":"115","author":"Bravo","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1001\/archinte.163.20.2433","article-title":"Depression and pain comorbidity: A literature review","volume":"163","author":"Bair","year":"2003","journal-title":"Arch. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.bbi.2014.04.003","article-title":"Neuropathic pain-induced depressive-like behavior and hippocampal neurogenesis and plasticity are dependent on TNFR1 signaling","volume":"41","author":"Dellarole","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1097\/j.pain.0000000000002549","article-title":"Long-term neuropathic pain behaviors correlate with synaptic plasticity and limbic circuit alteration: A comparative observational study in mice","volume":"163","author":"Guida","year":"2022","journal-title":"Pain"},{"key":"ref_24","first-page":"2398212819901082","article-title":"The role of the immune system in driving neuroinflammation","volume":"4","author":"Lynch","year":"2020","journal-title":"Brain Neurosci. Adv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3389\/fnins.2019.00213","article-title":"Brain Microglial Activation in Chronic Pain-Associated Affective Disorder","volume":"13","author":"Barcelon","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1152\/physrev.00039.2016","article-title":"Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa","volume":"98","author":"Dantzer","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev-pharmtox-010617-052823","article-title":"Inflammatory Mediators in Mood Disorders: Therapeutic Opportunities","volume":"58","author":"Pfau","year":"2018","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.psyneuen.2018.08.015","article-title":"Emerging role of the P2X7-NLRP3-IL1\u03b2 pathway in mood disorders","volume":"98","author":"Bhattacharya","year":"2018","journal-title":"Psychoneuroendocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10072-017-2875-z","article-title":"The prokineticin system: An interface between neural inflammation and pain","volume":"38","author":"Franchi","year":"2017","journal-title":"Neurol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1152\/physrev.00012.2017","article-title":"The Prokineticins: Neuromodulators and Mediators of Inflammation and Myeloid Cell-Dependent Angiogenesis","volume":"98","author":"Negri","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lattanzi, R., and Miele, R. (2021). Versatile Role of Prokineticins and Prokineticin Receptors in Neuroinflammation. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111648"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ito, H., Noda, K., Yoshida, K., Otani, K., Yoshiga, M., Oto, Y., Saito, S., and Kurosaka, D. (2016). Prokineticin 2 antagonist, PKRA7 suppresses arthritis in mice with collagen-induced arthritis. BMC Musculoskelet. Disord., 17.","DOI":"10.1186\/s12891-016-1243-0"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"18399","DOI":"10.1038\/s41598-021-97809-z","article-title":"Differential inflammation-mediated function of prokineticin 2 in the synovial fibroblasts of patients with rheumatoid arthritis compared with osteoarthritis","volume":"11","author":"Noda","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s00109-023-02307-6","article-title":"Blocking prokineticin receptors attenuates synovitis and joint destruction in collagen-induced arthritis","volume":"101","author":"Impellizzeri","year":"2023","journal-title":"J. Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Turati, M., Franchi, S., Crippa, M., Rizzi, L., Rigamonti, L., Sacerdote, P., Gatti, S.D., Piatti, M., Galimberti, G., and Munegato, D. (2023). Prokineticin 2 and Cytokine Content in the Synovial Fluid of Knee Osteoarthritis and Traumatic Meniscal Tear Patients: Preliminary Results. J. Clin. Med., 12.","DOI":"10.3390\/jcm12134330"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/npp.2008.61","article-title":"Disruption of the circadian output molecule prokineticin 2 results in anxiolytic and antidepressant-like effects in mice","volume":"34","author":"Li","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Amodeo, G., Verduci, B., Sartori, P., Procacci, P., Conte, V., Balboni, G., Sacerdote, P., and Franchi, S. (2021). The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910256"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"974","DOI":"10.3389\/fphar.2019.00974","article-title":"The Pharmacology of Pain Associated with the Monoiodoacetate Model of Osteoarthritis","volume":"10","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7122","DOI":"10.1038\/s41598-018-25581-8","article-title":"Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis","volume":"8","author":"Haywood","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_40","first-page":"53746","article-title":"The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse","volume":"111","author":"Pitcher","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Amodeo, G., Franchi, S., Galimberti, G., Comi, L., D\u2019Agnelli, S., Baciarello, M., Bignami, E.G., and Sacerdote, P. (2022). Osteoarthritis Pain in Old Mice Aggravates Neuroinflammation and Frailty: The Positive Effect of Morphine Treatment. Biomedicines, 10.","DOI":"10.3390\/biomedicines10112847"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7635","DOI":"10.1021\/jm800854e","article-title":"Triazine compounds as antagonists at Bv8-prokineticin receptors","volume":"5","author":"Balboni","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Rullo, L., Franchi, S., Amodeo, G., Caputi, F.F., Verduci, B., Losapio, L.M., Sacerdote, P., Romualdi, P., and Candeletti, S. (2021). Interplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111913"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ejphar.2014.05.048","article-title":"Efficacy of drugs with different mechanisms of action in relieving spontaneous pain at rest and during movement in a rat model of osteoarthritis","volume":"738","author":"Ishikawa","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.bbi.2019.09.012","article-title":"Prokineticin 2 promotes and sustains neuroinflammation in vincristine treated mice: Focus on pain and emotional like behavior","volume":"82","author":"Moschetti","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_46","first-page":"54052","article-title":"The Treadmill Fatigue Test: A Simple, High-throughput Assay of Fatigue-like Behavior for the Mouse","volume":"111","author":"Dougherty","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/ejn.14686","article-title":"How to study anxiety and depression in rodent models of chronic pain?","volume":"53","author":"Kremer","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1016\/j.joca.2015.06.021","article-title":"Deficiency of hyaluronan synthase 1 (Has1) results in chronic joint inflammation and widespread intra-articular fibrosis in a murine model of knee joint cartilage damage","volume":"23","author":"Chan","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bbi.2021.03.011","article-title":"Secretome of human adipose-derived mesenchymal stem cell relieves pain and neuroinflammation independently of the route of administration in experimental osteoarthritis","volume":"94","author":"Amodeo","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.bbi.2020.07.001","article-title":"Glial cell activation and altered metabolic profile in the spinal-trigeminal axis in a rat model of multiple sclerosis associated with the development of trigeminal sensitization","volume":"89","author":"Magni","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1242\/jcs.03168","article-title":"Loss of glial fibrillary acidic protein (GFAP) impairs Schwann cell proliferation and delays nerve regeneration after damage","volume":"119","author":"Triolo","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_52","first-page":"104","article-title":"Controlling the activation of the prokineticin system as therapeutic approach to relief neuropathic pain and reduce neuroinflammation","volume":"4","author":"Amodeo","year":"2022","journal-title":"Pharmadvances"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4850","DOI":"10.1111\/bph.12793","article-title":"Controlling the activation of the Bv8\/prokineticin system reduces neuroinflammation and abolishes thermal and tactile hyperalgesia in neuropathic animals","volume":"171","author":"Maftei","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.phrs.2014.11.004","article-title":"PC1, a non-peptide PKR1-preferring antagonist, reduces pain behavior and spinal neuronal sensitization in neuropathic mice","volume":"91","author":"Guida","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Castelli, M., Amodeo, G., Negri, L., Lattanzi, R., Maftei, D., Gotti, C., Pistillo, F., Onnis, V., Congu, C., and Panerai, A. (2016). Antagonism of the Prokineticin System Prevents and Reverses Allodynia and Inflammation in a Mouse Model of Diabetes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146259"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12974-019-1461-0","article-title":"Targeting prokineticin system counteracts hypersensitivity, neuroinflammation, and tissue damage in a mouse model of bortezomib-induced peripheral neuropathy","volume":"16","author":"Moschetti","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1002\/j.1532-2149.2012.00223.x","article-title":"Pain-like behaviour and spinal changes in the monosodium iodoacetate model of osteoarthritis in C57Bl\/6 mice","volume":"17","author":"Ogbonna","year":"2013","journal-title":"Eur. J. Pain"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9792","DOI":"10.1007\/s11357-015-9792-y","article-title":"Development of monosodium acetate-induced osteoarthritis and inflammatory pain in ageing mice","volume":"37","author":"Ogbonna","year":"2015","journal-title":"Age"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S1063-4584(03)00163-8","article-title":"Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis","volume":"11","author":"Bove","year":"2003","journal-title":"Osteoarthr. Cartil."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.pain.2004.08.004","article-title":"Pain related behaviour in two models of osteoarthritis in the rat knee","volume":"112","author":"Fernihough","year":"2004","journal-title":"Pain"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1124\/jpet.106.110387","article-title":"Prostacyclin antagonism reduces pain and inflammation in rodent models of hyperalgesia and chronic arthritis","volume":"319","author":"Pulichino","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1124\/jpet.110.167924","article-title":"Antinociceptive effects of AS1892802, a novel Rho kinase inhibitor, in rat models of inflammatory and noninflammatory arthritis","volume":"334","author":"Yoshimi","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.pbb.2010.11.003","article-title":"Gait analysis and pain response of two rodent models of osteoarthritis","volume":"97","author":"Ferland","year":"2011","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.vascn.2011.10.002","article-title":"Establishment of a novel objective and quantitative method to assess pain-related behavior in monosodium iodoacetate-induced osteoarthritis in rat knee","volume":"65","author":"Nagase","year":"2012","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2174\/157015906778019518","article-title":"Modulators of pain: Bv8 and prokineticins","volume":"4","author":"Negri","year":"2006","journal-title":"Curr. Neuropharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1074\/jbc.M116.756601","article-title":"Cytokine-induced MMP13 Expression in Human Chondrocytes Is Dependent on Activating Transcription Factor 3 (ATF3) Regulation","volume":"292","author":"Chan","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Hu, Q., and Ecker, M. (2021). Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041742"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s12974-017-0944-0","article-title":"Prophylactic inhibition of neutrophil elastase prevents the development of chronic neuropathic pain in osteoarthritic mice","volume":"14","author":"Muley","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/nature06348","article-title":"Bv8 regulates myeloid-cell-dependent tumour angiogenesis","volume":"450","author":"Shojaei","year":"2007","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"19574","DOI":"10.1074\/jbc.M111.326801","article-title":"Induction of Bv8 expression by granulocyte colony-stimulating factor in CD11b+Gr1+ cells: Key role of Stat3 signaling","volume":"287","author":"Qu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5882","DOI":"10.4049\/jimmunol.1201881","article-title":"IL-6 cooperates with G-CSF to induce protumor function of neutrophils in bone marrow by enhancing STAT3 activation","volume":"190","author":"Yan","year":"2013","journal-title":"J. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/brain\/awr025","article-title":"JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats","volume":"134","author":"Tsuda","year":"2011","journal-title":"Brain"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/papr.12551","article-title":"Degenerative Joint Diseases and Neuroinflammation","volume":"17","author":"Fusco","year":"2017","journal-title":"Pain Pract."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1111\/j.1471-4159.2006.03824.x","article-title":"Chronic pain-induced emotional dysfunction is associated with astrogliosis due to cortical delta-opioid receptor dysfunction","volume":"97","author":"Narita","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1213\/01.ane.0000261514.19946.66","article-title":"Experimental neuropathy in mice is associated with delayed behavioral changes related to anxiety and depression","volume":"104","author":"Suzuki","year":"2007","journal-title":"Anesth. Analg."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1007\/s00213-018-4950-4","article-title":"Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression","volume":"235","author":"Levy","year":"2018","journal-title":"Psychopharmacology"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Khan, A.R., Geiger, L., Wiborg, O., and Cz\u00e9h, B. (2020). Stress-Induced Morphological, Cellular and Molecular Changes in the Brain-Lessons Learned from the Chronic Mild Stress Model of Depression. Cells, 9.","DOI":"10.3390\/cells9041026"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5475","DOI":"10.1073\/pnas.1113363109","article-title":"Prokineticin 2 is an endangering mediator of cerebral ischemic injury","volume":"109","author":"Cheng","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"107739","DOI":"10.1016\/j.neuropharm.2019.107739","article-title":"The prokineticin receptor antagonist PC1 rescues memory impairment induced by \u03b2 amyloid administration through the modulation of prokineticin system","volume":"158","author":"Maftei","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"622","DOI":"10.3389\/fphar.2019.00622","article-title":"Chemokines in Alzheimer\u2019s Disease: New Insights into Prokineticins, Chemokine-Like Proteins","volume":"10","author":"Zuena","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"153432","DOI":"10.1016\/j.tox.2023.153432","article-title":"PK2\/PKRs pathway is involved in the protective effect of artemisinin against trimethyltin chloride-induced hippocampal injury","volume":"486","author":"Gao","year":"2023","journal-title":"Toxicology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"114147","DOI":"10.1016\/j.bcp.2020.114147","article-title":"Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective","volume":"180","author":"Bindu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Reynaud, D., Sergent, F., Abi Nahed, R., Traboulsi, W., Collet, C., Marquette, C., Hoffmann, P., Balboni, G., Zhou, Q.Y., and Murthi, P. (2021). Evidence-Based View of Safety and Effectiveness of Prokineticin Receptors Antagonists during Pregnancy. Biomedicines, 9.","DOI":"10.3390\/biomedicines9030309"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2255\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:49:15Z","timestamp":1760129355000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,12]]},"references-count":83,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cells12182255"],"URL":"https:\/\/doi.org\/10.3390\/cells12182255","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,12]]}}}