{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T19:50:17Z","timestamp":1780429817762,"version":"3.54.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Australian Research Council Linkage grant","award":["LP0668324"],"award-info":[{"award-number":["LP0668324"]}]},{"DOI":"10.13039\/501100020111","name":"Therapeutic Innovation Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020111","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Collaborative Research Infrastructure Strategy (NCRIS) programme"},{"name":"Australian Postgraduate Award"},{"DOI":"10.13039\/501100001794","name":"The University of Queensland","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001794","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflammopharmacol"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Post-herpetic neuralgia (PHN) is a type of neuropathic (nerve) pain that persists for more than 3\u00a0months after crusting of the last shingles lesion. It is difficult to relieve with analgesic\/adjuvant medications, and so novel analgesics are needed. Our aim was to use a rat model of varicella zoster virus (VZV)-induced neuropathic pain to assess the pain relief efficacy of several small molecule angiotensin II type 2 (AT<jats:sub>2<\/jats:sub>) receptor antagonists (PD123,319, EMA300, and EMA401) relative to clinically used analgesic\/adjuvant agents from four different pharmacological classes. Male Wistar rats received a unilateral intraplantar injection of VZV-infected MRC-5 cells (2\u2009\u00d7\u200910<jats:sup>4<\/jats:sup> infected cells) and paw withdrawal thresholds (PWTs) in the ipsilateral hindpaws were assessed using von Frey filaments. Animals with PWTs\u2009\u2264\u20098\u00a0g received single doses of PD123,319 (0.03\u20133\u00a0mg\/kg), EMA300 (0.3\u20135\u00a0mg\/kg), EMA401 (0.03\u20131\u00a0mg\/kg), gabapentin (10\u201360\u00a0mg\/kg), amitriptyline (5\u201330\u00a0mg\/kg), morphine (0.1\u20133\u00a0mg\/kg), meloxicam (5\u201320\u00a0mg\/kg) or vehicle and PWT versus time curves were generated. Single doses of PD123,319, EMA300, EMA401, gabapentin and morphine-evoked dose-dependent anti-allodynia in the hindpaws of VZV-rats. The mean (95% confidence intervals) ED<jats:sub>50<\/jats:sub>s were 0.57 (0.04\u20131.7), 2.5 (1.0\u20133.7) and 0.41 (0.12\u20130.87) mg\/kg for PD123,319, EMA300, and EMA401, respectively. The ED<jats:sub>50<\/jats:sub>s for gabapentin and morphine were 39.9 (25.1\u201364.8) and 0.04 (0.16\u20132.09) mg\/kg, respectively. In conclusion, the anti-allodynic efficacy of EMA401 in a VZV-rat model of neuropathic pain is aligned with its analgesic efficacy in a Phase 2a clinical trial in patients with PHN. This model has utility for anti-allodynic efficacy assessment of novel AT<jats:sub>2<\/jats:sub> receptor antagonists from drug discovery.<\/jats:p>","DOI":"10.1007\/s10787-025-01650-z","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T04:47:02Z","timestamp":1740026822000},"page":"1337-1348","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The angiotensin II type 2 receptor antagonists, PD123,319 ((S-(\u2009+)-1-[(4-(dimethylamino)-3-methylphenyl)methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid), EMA300 (5-(2,2-diphenylacetyl)-4-[(4-methoxy-3-methylphenyl)methyl]-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-6-carboxylic acid) and EMA401 ((3S)-5-(benzyloxy)-2-(2,2-diphenylacetyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid), evoke pain relief in a varicella zoster virus-induced rat model of neuropathic pain"],"prefix":"10.1007","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9899-6042","authenticated-orcid":false,"given":"V.","family":"Das","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3804-6563","authenticated-orcid":false,"given":"A. L.","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2281-3734","authenticated-orcid":false,"given":"M. T.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"1650_CR1","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1002\/j.1532-2149.2012.00269.x","volume":"17","author":"U Anand","year":"2013","unstructured":"Anand U, Facer P, Yiangou Y, Sinisi M, Fox M, Mccarthy T, Bountra C, Korchev YE, Anand P (2013) Angiotensin II type 2 receptor (At2 R) localization and antagonist-mediated inhibition of capsaicin responses and neurite outgrowth in human and rat sensory neurons. Eur J Pain 17:1012\u20131026","journal-title":"Eur J Pain"},{"key":"1650_CR2","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12990-015-0038-x","volume":"11","author":"U Anand","year":"2015","unstructured":"Anand U, Yiangou Y, Sinisi M, Fox M, Macquillan A, Quick T, Korchev YE, Bountra C, Mccarthy T, Anand P (2015) Mechanisms underlying clinical efficacy of angiotensin II type 2 receptor (At2r) antagonist Ema401 in neuropathic pain: clinical tissue and in vitro studies. Mol Pain 11:38","journal-title":"Mol Pain"},{"key":"1650_CR3","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.cell.2009.09.028","volume":"139","author":"AI Basbaum","year":"2009","unstructured":"Basbaum AI, Bautista DM, Scherrer G, Julius D (2009) Cellular and molecular mechanisms of pain. Cell 139:267\u2013284","journal-title":"Cell"},{"key":"1650_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s40122-022-00451-4","volume":"12","author":"X Cao","year":"2023","unstructured":"Cao X, Shen Z, Wang X, Zhao J, Liu W, Jiang G (2023) A meta-analysis of randomized controlled trials comparing the efficacy and safety of pregabalin and gabapentin in the treatment of postherpetic neuralgia. Pain Ther 12:1\u201318","journal-title":"Pain Ther"},{"key":"1650_CR5","doi-asserted-by":"publisher","first-page":"3452","DOI":"10.1210\/en.2008-0061","volume":"149","author":"A Chakrabarty","year":"2008","unstructured":"Chakrabarty A, Blacklock A, Svojanovsky S, Smith PG (2008) Estrogen elicits dorsal root ganglion axon sprouting via a renin-angiotensin system. Endocrinology 149:3452\u20133460","journal-title":"Endocrinology"},{"key":"1650_CR6","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.brainresrev.2004.07.008","volume":"46","author":"RG Dalziel","year":"2004","unstructured":"Dalziel RG, Bingham S, Sutton D, Grant D, Champion JM, Dennis SA, Quinn JP, Bountra C, Mark MA (2004) Allodynia in rats infected with varicella zoster virus\u2014a small animal model for post-herpetic neuralgia. Brain Res Brain Res Rev 46:234\u2013242","journal-title":"Brain Res Brain Res Rev"},{"key":"1650_CR7","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1212\/01.WNL.0000055433.55136.55","volume":"60","author":"RH Dworkin","year":"2003","unstructured":"Dworkin RH, Corbin AE, Young JP Jr, Sharma U, Lamoreaux L, Bockbrader H, Garofalo EA, Poole RM (2003) Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 60:1274\u20131283","journal-title":"Neurology"},{"key":"1650_CR8","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(14)70251-0","volume":"14","author":"NB Finnerup","year":"2015","unstructured":"Finnerup NB, Attal N, Haroutounian S, Mcnicol E, Baron R, Dworkin RH, Gilron I, Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M (2015) Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 14:162\u2013173","journal-title":"Lancet Neurol"},{"key":"1650_CR9","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.pain.2005.08.003","volume":"118","author":"EM Garry","year":"2005","unstructured":"Garry EM, Delaney A, Anderson HA, Sirinathsinghji EC, Clapp RH, Martin WJ, Kinchington PR, Krah DL, Abbadie C, Fleetwood-Walker SM (2005) Varicella zoster virus induces neuropathic changes in rat dorsal root ganglia and behavioral reflex sensitisation that is attenuated by gabapentin or sodium channel blocking drugs. Pain 118:97\u2013111","journal-title":"Pain"},{"key":"1650_CR10","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1210\/mend.13.9.0344","volume":"13","author":"L Gendron","year":"1999","unstructured":"Gendron L, Laflamme L, Rivard N, Asselin C, Payet MD, Gallo-Payet N (1999) Signals from the At2 (angiotensin type 2) receptor of angiotensin II inhibit P21ras and activate Mapk (mitogen-activated protein kinase) to induce morphological neuronal differentiation in Ng108-15 cells. Mol Endocrinol 13:1615\u20131626","journal-title":"Mol Endocrinol"},{"key":"1650_CR11","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.virol.2015.03.046","volume":"482","author":"JM Guedon","year":"2015","unstructured":"Guedon JM, Yee MB, Zhang M, Harvey SA, Goins WF, Kinchington PR (2015) Neuronal changes induced by varicella zoster virus in a rat model of postherpetic neuralgia. Virology 482:167\u2013180","journal-title":"Virology"},{"key":"1650_CR12","doi-asserted-by":"publisher","first-page":"15412","DOI":"10.1021\/acsomega.1c01866","volume":"6","author":"Y Guo","year":"2021","unstructured":"Guo Y, Huang X, Liao W, Meng L, Xu D, Ye C, Chen L, Hu T (2021) Discovery and optimization of highly potent and selective At(2)R antagonists to relieve peripheral neuropathic pain. ACS Omega 6:15412\u201315420","journal-title":"ACS Omega"},{"key":"1650_CR13","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1016\/j.neuroscience.2006.11.029","volume":"144","author":"FS Hasnie","year":"2007","unstructured":"Hasnie FS, Breuer J, Parker S, Wallace V, Blackbeard J, Lever I, Kinchington PR, Dickenson AH, Pheby T, Rice AS (2007) Further characterization of a rat model of varicella zoster virus-associated pain: relationship between mechanical hypersensitivity and anxiety-related behavior, and the influence of analgesic drugs. Neuroscience 144:1495\u20131508","journal-title":"Neuroscience"},{"key":"1650_CR14","doi-asserted-by":"publisher","first-page":"7413","DOI":"10.1021\/acs.analchem.0c04487","volume":"93","author":"D Higton","year":"2021","unstructured":"Higton D, Palmer ME, Vissers JPC, Mullin LG, Plumb RS, Wilson ID (2021) Use of cyclic ion mobility spectrometry (Cim)-mass spectrometry to study the intramolecular transacylation of diclofenac acyl glucuronide. Anal Chem 93:7413\u20137421","journal-title":"Anal Chem"},{"key":"1650_CR15","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1007\/s13365-011-0069-7","volume":"17","author":"PR Kinchington","year":"2011","unstructured":"Kinchington PR, Goins WF (2011) Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host and in rodent animal models. J Neurovirol 17:590\u2013599","journal-title":"J Neurovirol"},{"key":"1650_CR16","doi-asserted-by":"publisher","first-page":"16402","DOI":"10.1038\/s41598-018-34594-2","volume":"8","author":"S Koyama","year":"2018","unstructured":"Koyama S, Leblanc BW, Smith KA, Roach C, Levitt J, Edhi MM, Michishita M, Komatsu T, Mashita O, Tanikawa A, Yoshikawa S, Saab CY (2018) An electroencephalography bioassay for preclinical testing of analgesic efficacy. Sci Rep 8:16402","journal-title":"Sci Rep"},{"key":"1650_CR17","first-page":"67","volume":"37","author":"K Lambert","year":"1976","unstructured":"Lambert K, Pirt SJ (1976) The nutrient requirements of Mrc-5 human diploid cells. Dev Biol Stand 37:67\u201370","journal-title":"Dev Biol Stand"},{"key":"1650_CR18","doi-asserted-by":"publisher","DOI":"10.5070\/D328559238","author":"SL Menaldi","year":"2022","unstructured":"Menaldi SL, Halim PA, Kurniawan K (2022) Efficacy of gabapentinoids for acute herpes zoster in preventing postherpetic neuralgia: a systematic review of randomized controlled trials. Dermatol Online J. https:\/\/doi.org\/10.5070\/D328559238","journal-title":"Dermatol Online J"},{"key":"1650_CR19","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1111\/pme.12258","volume":"15","author":"A Muralidharan","year":"2014","unstructured":"Muralidharan A, Wyse BD, Smith MT (2014) Analgesic efficacy and mode of action of a selective small molecule angiotensin II type 2 receptor antagonist in a rat model of prostate cancer-induced bone pain. Pain Med 15:93\u2013110","journal-title":"Pain Med"},{"key":"1650_CR20","unstructured":"NHMRC (2013) Australian code for the care and use of animals for scientific purpose, 8th ed. Canberra: National Health and Medical Research Council, Australian Government"},{"issue":"Suppl 1","key":"1650_CR21","doi-asserted-by":"publisher","first-page":"S8","DOI":"10.1016\/S1386-6532(10)70003-2","volume":"48","author":"W Opstelten","year":"2010","unstructured":"Opstelten W, Mcelhaney J, Weinberger B, Oaklander AL, Johnson RW (2010) The impact of varicella zoster virus: chronic pain. J Clin Virol 48(Suppl 1):S8-13","journal-title":"J Clin Virol"},{"key":"1650_CR22","doi-asserted-by":"publisher","first-page":"4646","DOI":"10.1210\/en.2005-1315","volume":"147","author":"B Plouffe","year":"2006","unstructured":"Plouffe B, Guimond MO, Beaudry H, Gallo-Payet N (2006) Role of tyrosine kinase receptors in angiotensin II At2 receptor signaling: involvement in neurite outgrowth and in P42\/P44mapk activation in Ng108-15 cells. Endocrinology 147:4646\u20134654","journal-title":"Endocrinology"},{"key":"1650_CR23","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1016\/S0140-6736(13)62337-5","volume":"383","author":"ASC Rice","year":"2014","unstructured":"Rice ASC, Dworkin RH, Mccarthy TD, Anand P, Bountra C, Mccloud PI, Hill J, Cutter G, Kitson G, Desem N, Raff M, EMAS Group (2014) Ema401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomised, double-blind, placebo-controlled phase 2 clinical trial. Lancet 383:1637\u20131647","journal-title":"Lancet"},{"key":"1650_CR24","doi-asserted-by":"publisher","first-page":"2578","DOI":"10.1097\/j.pain.0000000000002252","volume":"162","author":"ASC Rice","year":"2021","unstructured":"Rice ASC, Dworkin RH, Finnerup NB, Attal N, Anand P, Freeman R, Piaia A, Callegari F, Doerr C, Mondal S, Narayanan N, Ecochard L, Flossbach Y, Pandhi S (2021) Efficacy and safety of Ema401 in peripheral neuropathic pain: results of 2 randomised, double-blind, phase 2 studies in patients with postherpetic neuralgia and painful diabetic neuropathy. Pain 162:2578\u20132589","journal-title":"Pain"},{"key":"1650_CR25","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1001\/jama.280.21.1837","volume":"280","author":"M Rowbotham","year":"1998","unstructured":"Rowbotham M, Harden N, Stacey B, Bernstein P, Magnus-Miller L (1998) Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA 280:1837\u20131842","journal-title":"JAMA"},{"key":"1650_CR26","doi-asserted-by":"publisher","first-page":"495","DOI":"10.3389\/fphar.2018.00495","volume":"9","author":"PA Shenoy","year":"2018","unstructured":"Shenoy PA, Kuo A, Khan N, Gorham L, Nicholson JR, Corradini L, Vetter I, Smith MT (2018) The somatostatin receptor-4 agonist J-2156 alleviates mechanical hypersensitivity in a rat model of breast cancer induced bone pain. Front Pharmacol 9:495","journal-title":"Front Pharmacol"},{"key":"1650_CR27","doi-asserted-by":"publisher","first-page":"7032","DOI":"10.1523\/JNEUROSCI.3542-17.2018","volume":"38","author":"AJ Shepherd","year":"2018","unstructured":"Shepherd AJ, Copits BA, Mickle AD, Karlsson P, Kadunganattil S, Haroutounian S, Tadinada SM, De Kloet AD, Valtcheva MV, Mcilvried LA, Sheahan TD, Jain S, Ray PR, Usachev YM, Dussor G, Krause EG, Price TJ, Gereau RWT, Mohapatra DP (2018) Angiotensin II triggers peripheral macrophage-to-sensory neuron redox crosstalk to elicit pain. J Neurosci 38:7032\u20137057","journal-title":"J Neurosci"},{"key":"1650_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2023.102415","volume":"73","author":"AJ Shepherd","year":"2023","unstructured":"Shepherd AJ, Rice AS, Smith MT (2023) Angiotensin II type 2 receptor signalling as a pain target: bench, bedside and back-translation. Curr Opin Pharmacol 73:102415","journal-title":"Curr Opin Pharmacol"},{"key":"1650_CR29","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1016\/S0149-2918(03)80111-X","volume":"25","author":"D Singh","year":"2003","unstructured":"Singh D, Kennedy DH (2003) The use of gabapentin for the treatment of postherpetic neuralgia. Clin Ther 25:852\u2013889","journal-title":"Clin Ther"},{"key":"1650_CR30","doi-asserted-by":"publisher","first-page":"S15","DOI":"10.1097\/j.pain.0000000000002675","volume":"163","author":"MT Smith","year":"2022","unstructured":"Smith MT (2022) Nonopioid analgesics discovery and the valley of death: Ema401 from concept to clinical trial. Pain 163:S15\u2013S28","journal-title":"Pain"},{"key":"1650_CR31","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1517\/14728222.2014.957673","volume":"19","author":"MT Smith","year":"2015","unstructured":"Smith MT, Muralidharan A (2015) Targeting angiotensin II type 2 receptor pathways to treat neuropathic pain and inflammatory pain. Expert Opin Ther Targets 19:25\u201335","journal-title":"Expert Opin Ther Targets"},{"key":"1650_CR32","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1111\/pme.12157","volume":"14","author":"MT Smith","year":"2013","unstructured":"Smith MT, Woodruff TM, Wyse BD, Muralidharan A, Walther T (2013a) A small molecule angiotensin II type 2 receptor (At(2)R) antagonist produces analgesia in a rat model of neuropathic pain by inhibition of P38 mitogen-activated protein kinase (Mapk) and P44\/P42 Mapk activation in the dorsal root ganglia. Pain Med 14:1557\u20131568","journal-title":"Pain Med"},{"key":"1650_CR33","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1111\/pme.12063","volume":"14","author":"MT Smith","year":"2013","unstructured":"Smith MT, Wyse BD, Edwards SR (2013b) Small molecule angiotensin II type 2 receptor (At(2)R) antagonists as novel analgesics for neuropathic pain: comparative pharmacokinetics, radioligand binding, and efficacy in rats. Pain Med 14:692\u2013705","journal-title":"Pain Med"},{"key":"1650_CR34","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1097\/FBP.0000000000000025","volume":"25","author":"MT Smith","year":"2014","unstructured":"Smith MT, Lau T, Wallace VC, Wyse BD, Rice AS (2014) Analgesic efficacy of small-molecule angiotensin II type 2 receptor antagonists in a rat model of antiretroviral toxic polyneuropathy. Behav Pharmacol 25:137\u2013146","journal-title":"Behav Pharmacol"},{"key":"1650_CR35","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0169-328X(00)00093-0","volume":"78","author":"U Stroth","year":"2000","unstructured":"Stroth U, Blume A, Mielke K, Unger T (2000) Angiotensin At(2) receptor stimulates Erk1 and Erk2 in quiescent but inhibits Erk in Ngf-stimulated Pc12w cells. Brain Res Mol Brain Res 78:175\u2013180","journal-title":"Brain Res Mol Brain Res"},{"key":"1650_CR36","doi-asserted-by":"publisher","first-page":"5376","DOI":"10.1038\/s41598-021-84882-7","volume":"11","author":"K Uemura","year":"2021","unstructured":"Uemura K, Sasaki M, Sanaki T, Toba S, Takahashi Y, Orba Y, Hall WW, Maenaka K, Sawa H, Sato A (2021) Mrc5 cells engineered to express Ace2 serve as a model system for the discovery of antivirals targeting Sars-Cov-2. Sci Rep 11:5376","journal-title":"Sci Rep"},{"key":"1650_CR37","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1007\/s10787-022-01076-x","volume":"30","author":"TN Vieira","year":"2022","unstructured":"Vieira TN, Saraiva ALL, Guimaraes RM, Luiz JPM, Pinto LG, De Melo Rodrigues Avila V, Goulart LR, Cunha-Junior JP, Mcnaughton PA, Cunha TM, Ferreira J, Silva CR (2022) Angiotensin type 2 receptor antagonism as a new target to manage gout. Inflammopharmacology 30:2399\u20132410","journal-title":"Inflammopharmacology"}],"container-title":["Inflammopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-025-01650-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10787-025-01650-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-025-01650-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T13:17:12Z","timestamp":1742303832000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10787-025-01650-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,20]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["1650"],"URL":"https:\/\/doi.org\/10.1007\/s10787-025-01650-z","relation":{},"ISSN":["0925-4692","1568-5608"],"issn-type":[{"value":"0925-4692","type":"print"},{"value":"1568-5608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,20]]},"assertion":[{"value":"20 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"VD and ALL have no declarations of interest to disclose. In the past 3-years, MTS has collaborated with Boehringer Ingelheim Pharma GmbH & Co. KG, Argenica Therapeutics and Allay Therapeutics, on contract-funded collaborative research projects unrelated to the topic of this research. MTS is also cofounder of the UQ spin-out company, Cassowary Pharmaceuticals, aimed at discovery of novel therapeutics for the relief of chronic pain.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}