{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:10:32Z","timestamp":1790691032009,"version":"4.1.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Given possible involvement of the central and peripheral angiotensin system in pain processing, we conducted clinical and preclinical studies to test whether pharmacological inhibition of the angiotensin system would prevent diabetic peripheral neuropathy (DPN) accompanying type 2 diabetes mellitus (T2DM). In the preclinical study, the nociceptive sensitivity was determined in leptin-deficient <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> mice, a T2DM model. A clinical retrospective cohort study was conducted, using the medical records of T2DM patients receiving antihypertensives at three hospitals for nearly a decade. In the <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> mice, daily treatment with perindopril, an angiotensin-converting enzyme inhibitor (ACEI), or telmisartan, an angiotensin receptor blocker (ARB), but not amlodipine, an L-type calcium channel blocker (CaB), significantly inhibited DPN development without affecting the hyperglycemia. In the clinical study, the enrolled 7464 patients were divided into three groups receiving ACEIs, ARBs and the others (non-ACEI, non-ARB antihypertensives). Bonferroni\u2019s test indicated significantly later DPN development in the ARB and ACEI groups than the others group. The multivariate Cox proportional analysis detected significant negative association of the prescription of ACEIs or ARBs and \u03b2-blockers, but not CaBs or diuretics, with DPN development. Thus, our study suggests that pharmacological inhibition of the angiotensin system is beneficial to prevent DPN accompanying T2DM.<\/jats:p>","DOI":"10.1038\/s41598-024-51572-z","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T17:02:37Z","timestamp":1704906157000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Clinical and preclinical evidence that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prevent diabetic peripheral neuropathy"],"prefix":"10.1038","volume":"14","author":[{"given":"Shiori","family":"Iwane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Nemoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyoshi","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Uchitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Muranaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Fujitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Koizumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maho","family":"Tsubota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiko","family":"Sekiguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Tan-No","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsufumi","family":"Kawabata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"51572_CR1","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/s12933-023-01862-z","volume":"22","author":"M Shi","year":"2023","unstructured":"Shi, M. et al. Identification of candidate metabolite biomarkers for metabolic syndrome and its five components in population-based human cohorts. Cardiovasc. Diabetol. 22, 141 (2023).","journal-title":"Cardiovasc. Diabetol."},{"key":"51572_CR2","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1161\/HYPERTENSIONAHA.116.08560","volume":"69","author":"Z Wang","year":"2017","unstructured":"Wang, Z. et al. Synergistic interaction of hypertension and diabetes in promoting kidney injury and the role of endoplasmic reticulum stress. Hypertension 69, 879\u2013891 (2017).","journal-title":"Hypertension"},{"key":"51572_CR3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s12882-021-02587-5","volume":"23","author":"D Banerjee","year":"2022","unstructured":"Banerjee, D. et al. Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British clinical diabetologists and the renal association UK guideline update 2021. BMC Nephrol. 23, 9 (2022).","journal-title":"BMC Nephrol."},{"key":"51572_CR4","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.pcd.2019.12.005","volume":"14","author":"J Sun","year":"2020","unstructured":"Sun, J., Wang, Y., Zhang, X., Zhu, S. & He, H. Prevalence of peripheral neuropathy in patients with diabetes: A systematic review and meta-analysis. Prim. Care Diabetes 14, 435\u2013444 (2020).","journal-title":"Prim. Care Diabetes"},{"key":"51572_CR5","doi-asserted-by":"publisher","first-page":"755","DOI":"10.3390\/biology12050755","volume":"12","author":"W Nemoto","year":"2023","unstructured":"Nemoto, W., Yamagata, R., Nakagawasai, O. & Tan-No, K. Angiotensin-related peptides and their role in pain regulation. Biology 12, 755 (2023).","journal-title":"Biology"},{"key":"51572_CR6","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1124\/mol.116.104133","volume":"90","author":"Y Ogata","year":"2016","unstructured":"Ogata, Y. et al. Involvement of spinal angiotensin II system in streptozotocin-induced diabetic neuropathic pain in mice. Mol. Pharmacol. 90, 205\u2013213 (2016).","journal-title":"Mol. Pharmacol."},{"key":"51572_CR7","doi-asserted-by":"publisher","first-page":"113825","DOI":"10.1016\/j.bcp.2020.113825","volume":"174","author":"R Yamagata","year":"2020","unstructured":"Yamagata, R., Nemoto, W., Nakagawasai, O., Takahashi, K. & Tan-No, K. Downregulation of spinal angiotensin converting enzyme 2 is involved in neuropathic pain associated with type 2 diabetes mellitus in mice. Biochem. Pharmacol. 174, 113825 (2020).","journal-title":"Biochem. Pharmacol."},{"key":"51572_CR8","doi-asserted-by":"publisher","first-page":"2939","DOI":"10.3390\/jcm11102939","volume":"11","author":"S Frachet","year":"2022","unstructured":"Frachet, S. et al. Renin-angiotensin-system inhibitors for the prevention of chemotherapy-induced peripheral neuropathy: OncoToxSRA, a preliminary cohort study. J. Clin. Med. 11, 2939 (2022).","journal-title":"J. Clin. Med."},{"key":"51572_CR9","doi-asserted-by":"publisher","first-page":"7408","DOI":"10.1007\/s12035-019-1616-0","volume":"56","author":"E Kim","year":"2019","unstructured":"Kim, E., Hwang, S. H., Kim, H. K., Abdi, S. & Kim, H. K. Losartan, an angiotensin II type 1 receptor antagonist, alleviates mechanical hyperalgesia in a rat model of chemotherapy-induced neuropathic pain by inhibiting inflammatory cytokines in the dorsal root ganglia. Mol. Neurobiol. 56, 7408\u20137419 (2019).","journal-title":"Mol. Neurobiol."},{"key":"51572_CR10","doi-asserted-by":"publisher","first-page":"7949","DOI":"10.1111\/jcmm.15427","volume":"24","author":"N Kalynovska","year":"2020","unstructured":"Kalynovska, N., Diallo, M., Sotakova-Kasparova, D. & Palecek, J. Losartan attenuates neuroinflammation and neuropathic pain in paclitaxel-induced peripheral neuropathy. J. Cell Mol. Med. 24, 7949\u20137958 (2020).","journal-title":"J. Cell Mol. Med."},{"key":"51572_CR11","doi-asserted-by":"publisher","first-page":"7032","DOI":"10.1523\/JNEUROSCI.3542-17.2018","volume":"38","author":"AJ Shepherd","year":"2018","unstructured":"Shepherd, A. J. et al. Angiotensin II triggers peripheral macrophage-to-sensory neuron redox crosstalk to elicit pain. J. Neurosci. 38, 7032\u20137057 (2018).","journal-title":"J. Neurosci."},{"key":"51572_CR12","doi-asserted-by":"publisher","first-page":"E8057","DOI":"10.1073\/pnas.1721815115","volume":"115","author":"AJ Shepherd","year":"2018","unstructured":"Shepherd, A. J. et al. Macrophage angiotensin II type 2 receptor triggers neuropathic pain. Proc. Natl. Acad. Sci. 115, E8057\u2013E8066 (2018).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"51572_CR13","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1016\/S0140-6736(13)62337-5","volume":"383","author":"ASC Rice","year":"2014","unstructured":"Rice, A. S. C. et al. 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 (2014).","journal-title":"Lancet"},{"key":"51572_CR14","doi-asserted-by":"publisher","first-page":"2578","DOI":"10.1097\/j.pain.0000000000002252","volume":"162","author":"ASC Rice","year":"2021","unstructured":"Rice, A. S. C. et al. 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 (2021).","journal-title":"Pain"},{"key":"51572_CR15","doi-asserted-by":"publisher","first-page":"389","DOI":"10.3389\/fnmol.2017.00389","volume":"10","author":"N Khan","year":"2017","unstructured":"Khan, N., Muralidharan, A. & Smith, M. T. Attenuation of the infiltration of angiotensin II expressing CD3+ T-cells and the modulation of nerve growth factor in lumbar dorsal root ganglia: A possible mechanism underpinning analgesia produced by EMA300, an angiotensin II type 2 (AT2) receptor antagonist. Front. Mol. Neurosci. 10, 389 (2017).","journal-title":"Front. Mol. Neurosci."},{"key":"51572_CR16","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1210\/endo-88-5-1230","volume":"88","author":"SM Genuth","year":"1971","unstructured":"Genuth, S. M., Przybylski, R. J. & Rosenberg, D. M. Insulin resistance in genetically obese, hyperglycemic mice. Endocrinology 88, 1230\u20131238 (1971).","journal-title":"Endocrinology"},{"key":"51572_CR17","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/372425a0","volume":"372","author":"Y Zhang","year":"1994","unstructured":"Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425\u2013432 (1994).","journal-title":"Nature"},{"key":"51572_CR18","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0165-0270(94)90144-9","volume":"53","author":"SR Chaplan","year":"1994","unstructured":"Chaplan, S. R., Bach, F. W., Pogrel, J. W., Chung, J. M. & Yaksh, T. L. Quantitative assessment of tactile allodynia in the rat paw. J. Neurosci. Methods 53, 55\u201363 (1994).","journal-title":"J. Neurosci. Methods"},{"key":"51572_CR19","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.2337\/db07-1212","volume":"57","author":"C Tikellis","year":"2008","unstructured":"Tikellis, C. et al. ACE2 deficiency modifies renoprotection afforded by ACE inhibition in experimental diabetes. Diabetes 57, 1018\u20131025 (2008).","journal-title":"Diabetes"},{"key":"51572_CR20","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/hr.2011.176","volume":"35","author":"H Fujita","year":"2012","unstructured":"Fujita, H. et al. Modulation of renal superoxide dismutase by telmisartan therapy in C57BL\/6-Ins2(Akita) diabetic mice. Hypertens. Res. 35, 213\u2013220 (2012).","journal-title":"Hypertens. Res."},{"key":"51572_CR21","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1291\/hypres.29.457","volume":"29","author":"T Yoshii","year":"2006","unstructured":"Yoshii, T. et al. Regression of atherosclerosis by amlodipine via anti-inflammatory and anti-oxidative stress actions. Hypertens. Res. 29, 457\u2013466 (2006).","journal-title":"Hypertens. Res."},{"key":"51572_CR22","doi-asserted-by":"publisher","first-page":"2285","DOI":"10.2337\/dc10-1303","volume":"33","author":"S Tesfaye","year":"2010","unstructured":"Tesfaye, S. et al. Diabetic neuropathies: Update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33, 2285\u20132293 (2010).","journal-title":"Diabetes Care"},{"key":"51572_CR23","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/bmt.2012.244","volume":"48","author":"Y Kanda","year":"2013","unstructured":"Kanda, Y. Investigation of the freely available easy-to-use software \u201cEZR\u201d for medical statistics. Bone Marrow Transplant. 48, 452\u2013458 (2013).","journal-title":"Bone Marrow Transplant."},{"key":"51572_CR24","doi-asserted-by":"publisher","first-page":"24099","DOI":"10.18632\/oncotarget.15732","volume":"8","author":"Q Gao","year":"2017","unstructured":"Gao, Q. et al. Azilsartan ameliorates apoptosis of dopaminergic neurons and rescues characteristic parkinsonian behaviors in a rat model of Parkinson\u2019s disease. Oncotarget 8, 24099\u201324109 (2017).","journal-title":"Oncotarget"},{"key":"51572_CR25","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1016\/j.nucmedbio.2012.06.012","volume":"39","author":"A Noda","year":"2012","unstructured":"Noda, A. et al. Brain penetration of telmisartan, a unique centrally acting angiotensin II type 1 receptor blocker, studied by PET in conscious rhesus macaques. Nucl. Med. Biol. 39, 1232\u20131235 (2012).","journal-title":"Nucl. Med. Biol."},{"key":"51572_CR26","doi-asserted-by":"publisher","first-page":"2911","DOI":"10.1096\/fj.11-182873","volume":"25","author":"YF Dong","year":"2011","unstructured":"Dong, Y. F. et al. Perindopril, a centrally active angiotensin-converting enzyme inhibitor, prevents cognitive impairment in mouse models of Alzheimer\u2019s disease. FASEB J. 25, 2911\u20132920 (2011).","journal-title":"FASEB J."},{"key":"51572_CR27","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1124\/jpet.105.092080","volume":"316","author":"M Nozawa","year":"2006","unstructured":"Nozawa, M., Sugimoto, K., Ohmori, M., Ando, H. & Fujimura, A. Dosing time-dependent effect of temocapril on the mortality of stroke-prone spontaneously hypertensive rats. J. Pharmacol. Exp. Ther. 316, 176\u2013181 (2006).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"51572_CR28","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1291\/hypres.27.213","volume":"27","author":"S Takai","year":"2004","unstructured":"Takai, S., Jin, D., Sakaguchi, M. & Miyazaki, M. Significant target organs for hypertension and cardiac hypertrophy by angiotensin-converting enzyme inhibitors. Hypertens. Res. 27, 213\u2013219 (2004).","journal-title":"Hypertens. Res."},{"key":"51572_CR29","doi-asserted-by":"publisher","first-page":"e000923","DOI":"10.1136\/lupus-2023-000923","volume":"10","author":"C Dobrowolski","year":"2023","unstructured":"Dobrowolski, C. et al. Centrally acting ACE inhibitor (cACEi) and angiotensin receptor blocker (cARB) use and cognitive dysfunction in patients with SLE. Lupus Sci. Med. 10, e000923 (2023).","journal-title":"Lupus Sci. Med."},{"key":"51572_CR30","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1001\/archinternmed.2009.175","volume":"169","author":"KM Sink","year":"2009","unstructured":"Sink, K. M. et al. Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension: Results from the cardiovascular health study. Arch. Intern. Med. 169, 1195\u20131202 (2009).","journal-title":"Arch. Intern. Med."},{"key":"51572_CR31","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1111\/nep.13860","volume":"26","author":"M Sugahara","year":"2021","unstructured":"Sugahara, M., Pak, W. L. W., Tanaka, T., Tang, S. C. W. & Nangaku, M. Update on diagnosis, pathophysiology, and management of diabetic kidney disease. Nephrology 26, 491\u2013500 (2021).","journal-title":"Nephrology"},{"key":"51572_CR32","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s00424-021-02651-x","volume":"474","author":"V Sukumaran","year":"2022","unstructured":"Sukumaran, V., Gurusamy, N., Yalcin, H. C. & Venkatesh, S. Understanding diabetes-induced cardiomyopathy from the perspective of renin angiotensin aldosterone system. Pflugers Arch. 474, 63\u201381 (2022).","journal-title":"Pflugers Arch."},{"key":"51572_CR33","doi-asserted-by":"publisher","first-page":"1978","DOI":"10.1016\/S0140-6736(98)02478-7","volume":"352","author":"RA Malik","year":"1998","unstructured":"Malik, R. A. et al. Effect of angiotensin-converting-enzyme (ACE) inhibitor trandolapril on human diabetic neuropathy: Randomised double-blind controlled trial. Lancet 352, 1978\u20131981 (1998).","journal-title":"Lancet"},{"key":"51572_CR34","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1056\/NEJMoa032782","volume":"352","author":"S Tesfaye","year":"2005","unstructured":"Tesfaye, S. et al. Vascular risk factors and diabetic neuropathy. N. Engl. J. Med. 352, 341\u2013350 (2005).","journal-title":"N. Engl. J. Med."},{"key":"51572_CR35","doi-asserted-by":"publisher","first-page":"665","DOI":"10.2337\/diab.46.4.665","volume":"46","author":"KY Forrest","year":"1997","unstructured":"Forrest, K. Y., Maser, R. E., Pambianco, G., Becker, D. J. & Orchard, T. J. Hypertension as a risk factor for diabetic neuropathy: A prospective study. Diabetes 46, 665\u2013670 (1997).","journal-title":"Diabetes"},{"key":"51572_CR36","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1093\/ajh\/hpz058","volume":"32","author":"G Ponirakis","year":"2019","unstructured":"Ponirakis, G. et al. Hypertension contributes to neuropathy in patients with type 1 diabetes. Am. J. Hypertens. 32, 796\u2013803 (2019).","journal-title":"Am. J. Hypertens."},{"key":"51572_CR37","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1046\/j.1523-1755.2002.00213.x","volume":"61","author":"RW Schrier","year":"2002","unstructured":"Schrier, R. W., Estacio, R. O., Esler, A. & Mehler, P. Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney Int. 61, 1086\u20131097 (2002).","journal-title":"Kidney Int."},{"key":"51572_CR38","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1016\/S0140-6736(07)61303-8","volume":"370","author":"A Patel","year":"2007","unstructured":"Patel, A. et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): A randomised controlled trial. Lancet 370, 829\u2013840 (2007).","journal-title":"Lancet"},{"key":"51572_CR39","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.jdiacomp.2005.07.010","volume":"20","author":"JW Stephens","year":"2006","unstructured":"Stephens, J. W., Dhamrait, S. S., Acharya, J., Humphries, S. E. & Hurel, S. J. A common variant in the ACE gene is associated with peripheral neuropathy in women with type 2 diabetes mellitus. J. Diabetes Complicat. 20, 317\u2013321 (2006).","journal-title":"J. Diabetes Complicat."},{"key":"51572_CR40","doi-asserted-by":"publisher","first-page":"143","DOI":"10.5812\/nephropathol.8109","volume":"1","author":"Z Rahimi","year":"2012","unstructured":"Rahimi, Z. ACE insertion\/deletion (I\/D) polymorphism and diabetic nephropathy. J. Nephropathol. 1, 143\u2013151 (2012).","journal-title":"J. Nephropathol."},{"key":"51572_CR41","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.gene.2013.07.095","volume":"529","author":"X Liang","year":"2013","unstructured":"Liang, X. et al. Polymorphism of angiotensinogen gene M235T in myocardial infarction and brain infarction: A meta-analysis. Gene 529, 73\u201379 (2013).","journal-title":"Gene"},{"key":"51572_CR42","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1177\/147323000203000502","volume":"30","author":"H Ito","year":"2002","unstructured":"Ito, H. et al. Angiotensin-converting enzyme insertion\/deletion polymorphism and polyneuropathy in type 2 diabetes without macroalbuminuria. J. Int. Med. Res. 30, 476\u2013482 (2002).","journal-title":"J. Int. Med. Res."},{"key":"51572_CR43","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.brainres.2008.09.099","volume":"1246","author":"J Pavel","year":"2008","unstructured":"Pavel, J. et al. Expression and transport of Angiotensin II AT1 receptors in spinal cord, dorsal root ganglia and sciatic nerve of the rat. Brain Res. 1246, 111\u2013122 (2008).","journal-title":"Brain Res."},{"key":"51572_CR44","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1007\/s11011-021-00728-1","volume":"36","author":"G Mirzahosseini","year":"2021","unstructured":"Mirzahosseini, G., Ismael, S., Ahmed, H. A. & Ishrat, T. Manifestation of renin angiotensin system modulation in traumatic brain injury. Metab. Brain Dis. 36, 1079\u20131086 (2021).","journal-title":"Metab. Brain Dis."},{"key":"51572_CR45","doi-asserted-by":"publisher","first-page":"9524635","DOI":"10.1155\/2020\/9524635","volume":"2020","author":"L Pang","year":"2020","unstructured":"Pang, L. et al. Understanding diabetic neuropathy: Focus on oxidative stress. Oxid. Med. Cell Longev. 2020, 9524635 (2020).","journal-title":"Oxid. Med. Cell Longev."},{"key":"51572_CR46","doi-asserted-by":"publisher","first-page":"e00209","DOI":"10.1002\/edm2.209","volume":"4","author":"S Alkhudhayri","year":"2021","unstructured":"Alkhudhayri, S. et al. Investigating the beneficial effect of aliskiren in attenuating neuropathic pain in diabetic Sprague-Dawley rats. Endocrinol. Diabetes Metab. 4, e00209 (2021).","journal-title":"Endocrinol. Diabetes Metab."},{"key":"51572_CR47","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1124\/mol.107.041707","volume":"73","author":"RM Pabbidi","year":"2008","unstructured":"Pabbidi, R. M., Cao, D. S., Parihar, A., Pauza, M. E. & Premkumar, L. S. Direct role of streptozotocin in inducing thermal hyperalgesia by enhanced expression of transient receptor potential vanilloid 1 in sensory neurons. Mol. Pharmacol. 73, 995\u20131004 (2008).","journal-title":"Mol. Pharmacol."},{"key":"51572_CR48","doi-asserted-by":"publisher","first-page":"15185","DOI":"10.1074\/jbc.M115.644476","volume":"290","author":"DA Andersson","year":"2015","unstructured":"Andersson, D. A. et al. Streptozotocin stimulates the ion channel TRPA1 directly: Involvement of peroxynitrite. J. Biol. Chem. 290, 15185\u201315196 (2015).","journal-title":"J. Biol. Chem."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-51572-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-51572-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-51572-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T18:06:03Z","timestamp":1704909963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-51572-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,10]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["51572"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-51572-z","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,10]]},"assertion":[{"value":"3 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 January 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1039"}}