{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:19:16Z","timestamp":1771471156542,"version":"3.50.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T00:00:00Z","timestamp":1593129600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T00:00:00Z","timestamp":1593129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The harmful effects of excessive mechanical loading on diabetic neuropathy and the reason diabetic neuropathic symptoms are common in feet are unclear. In this study, the hind paw suspension treadmill exercise model was used in rats to investigate whether mechanical loading applied to the front paws precipitates neuropathic pain, especially in diabetic conditions. Thirty-two rats were divided into six groups according to the presence of diabetes (DM) and the intensity of mechanical loading\u00a0applied to the front paws: DM-Hi (high-intensity); DM-Lo (low-intensity); DM-No (non-mechanical loading); Sham-Hi; Sham-Lo; and Sham-No. DM was induced by streptozotocin injection. For high-intensity or low-intensity mechanical loading, treadmill walking exercise was conducted with or without hind paw suspension, respectively. The mechanical withdrawal threshold of the front paw decreased significantly after 8\u00a0weeks only in the DM mechanical loading groups (DM-Hi and DM-Lo), and high-intensity loading more significantly decreased the front-paw withdrawal threshold than low-intensity loading. In the DM-Hi group\u00a0only, macrophage migration inhibitory factor (MIF) increased significantly, and intra-epidermal nerve fibers (IENF) in the front paws decreased significantly. In diabetic conditions, mechanical overloading such as excessive walking is likely to precipitate mechanical allodynia and damage IENF\u00b8 which could explain why diabetic neuropathic symptoms are common in feet. This finding might be related to up-regulation of intracellular signaling cascades such as MIF, rather than inflammatory processes.<\/jats:p>","DOI":"10.1038\/s41598-020-67601-6","type":"journal-article","created":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T10:19:43Z","timestamp":1593166783000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Excessive walking exercise precipitates diabetic neuropathic foot pain: hind paw suspension treadmill exercise experiment in a rat model"],"prefix":"10.1038","volume":"10","author":[{"given":"Jong Geol","family":"Do","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun Up","family":"Noh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seoung Wan","family":"Chae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung Jae","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Taek","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,26]]},"reference":[{"key":"67601_CR1","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.phrs.2013.12.005","volume":"80","author":"R Singh","year":"2014","unstructured":"Singh, R., Kishore, L. & Kaur, N. Diabetic peripheral neuropathy: Current perspective and future directions. Pharmacol. Res. 80, 21\u201335. https:\/\/doi.org\/10.1016\/j.phrs.2013.12.005 (2014).","journal-title":"Pharmacol. Res."},{"key":"67601_CR2","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1053\/j.semvascsurg.2012.04.009","volume":"25","author":"AJ Boulton","year":"2012","unstructured":"Boulton, A. J. Diabetic neuropathy: Is pain God\u2019s greatest gift to mankind?. Semin. Vasc. Surg. 25, 61\u201365. https:\/\/doi.org\/10.1053\/j.semvascsurg.2012.04.009 (2012).","journal-title":"Semin. Vasc. Surg."},{"key":"67601_CR3","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.tins.2013.04.008","volume":"36","author":"J Zenker","year":"2013","unstructured":"Zenker, J., Ziegler, D. & Chrast, R. Novel pathogenic pathways in diabetic neuropathy. Trends Neurosci. 36, 439\u2013449. https:\/\/doi.org\/10.1016\/j.tins.2013.04.008 (2013).","journal-title":"Trends Neurosci."},{"key":"67601_CR4","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/s1474-4422(12)70065-0","volume":"11","author":"BC Callaghan","year":"2012","unstructured":"Callaghan, B. C., Cheng, H. T., Stables, C. L., Smith, A. L. & Feldman, E. L. Diabetic neuropathy: Clinical manifestations and current treatments. Lancet Neurol. 11, 521\u2013534. https:\/\/doi.org\/10.1016\/s1474-4422(12)70065-0 (2012).","journal-title":"Lancet Neurol."},{"key":"67601_CR5","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.jchemneu.2013.10.001","volume":"53","author":"M Boric","year":"2013","unstructured":"Boric, M. et al. Reduced epidermal thickness, nerve degeneration and increased pain-related behavior in rats with diabetes type 1 and 2. J. Chem. Neuroanat. 53, 33\u201340. https:\/\/doi.org\/10.1016\/j.jchemneu.2013.10.001 (2013).","journal-title":"J. Chem. Neuroanat."},{"key":"67601_CR6","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1007\/s00125-005-1828-x","volume":"48","author":"R Meerwaldt","year":"2005","unstructured":"Meerwaldt, R. et al. Increased accumulation of skin advanced glycation end-products precedes and correlates with clinical manifestation of diabetic neuropathy. Diabetologia 48, 1637\u20131644. https:\/\/doi.org\/10.1007\/s00125-005-1828-x (2005).","journal-title":"Diabetologia"},{"key":"67601_CR7","doi-asserted-by":"publisher","first-page":"e80436","DOI":"10.1371\/journal.pone.0080436","volume":"8","author":"ZC Thent","year":"2013","unstructured":"Thent, Z. C., Das, S. & Henry, L. J. Role of exercise in the m***anagement of diabetes mellitus: The global scenario. PLoS ONE 8, e80436. https:\/\/doi.org\/10.1371\/journal.pone.0080436 (2013).","journal-title":"PLoS ONE"},{"key":"67601_CR8","doi-asserted-by":"publisher","first-page":"673","DOI":"10.7861\/clinmedicine.14-6-673","volume":"14","author":"A Lumb","year":"2014","unstructured":"Lumb, A. Diabetes and exercise. Clin. Med. (Lond., Engl.) 14, 673\u2013676. https:\/\/doi.org\/10.7861\/clinmedicine.14-6-673 (2014).","journal-title":"Clin. Med. (Lond., Engl.)"},{"key":"67601_CR9","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1249\/MSS.0b013e3181d58e09","volume":"42","author":"WS Kim","year":"2010","unstructured":"Kim, W. S. & Lee, S. U. Harmful effect of land-based endurance exercise in rats with diabetic nerve. Med. Sci. Sports Exerc. 42, 1625\u20131631. https:\/\/doi.org\/10.1249\/MSS.0b013e3181d58e09 (2010).","journal-title":"Med. Sci. Sports Exerc."},{"key":"67601_CR10","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.expneurol.2012.04.018","volume":"236","author":"JK Alexander","year":"2012","unstructured":"Alexander, J. K. et al. Macrophage migration inhibitory factor (MIF) is essential for inflammatory and neuropathic pain and enhances pain in response to stress. . Neurol. 236, 351\u2013362. https:\/\/doi.org\/10.1016\/j.expneurol.2012.04.018 (2012).","journal-title":". Neurol."},{"key":"67601_CR11","doi-asserted-by":"publisher","first-page":"73","DOI":"10.5604\/20831862.1093775","volume":"31","author":"JS Kim","year":"2014","unstructured":"Kim, J. S. et al. Effect of exercise training of different intensities on anti-inflammatory reaction in streptozotocin-induced diabetic rats. Biol. Sport. 31, 73\u201379. https:\/\/doi.org\/10.5604\/20831862.1093775 (2014).","journal-title":"Biol. Sport."},{"key":"67601_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pharmthera.2008.05.005","volume":"120","author":"JL Edwards","year":"2008","unstructured":"Edwards, J. L., Vincent, A. M., Cheng, H. T. & Feldman, E. L. Diabetic neuropathy: Mechanisms to management. Pharmacol. Ther. 120, 1\u201334. https:\/\/doi.org\/10.1016\/j.pharmthera.2008.05.005 (2008).","journal-title":"Pharmacol. Ther."},{"key":"67601_CR13","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.2337\/diab.35.9.1058","volume":"35","author":"H Nukada","year":"1986","unstructured":"Nukada, H. Increased susceptibility to ischemic damage in streptozocin-diabetic nerve. Diabetes 35, 1058\u20131061. https:\/\/doi.org\/10.2337\/diab.35.9.1058 (1986).","journal-title":"Diabetes"},{"key":"67601_CR14","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1002\/mus.880151010","volume":"15","author":"H Nukada","year":"1992","unstructured":"Nukada, H. Mild ischemia causes severe pathological changes in experimental diabetic nerve. Muscle Nerve 15, 1116\u20131122. https:\/\/doi.org\/10.1002\/mus.880151010 (1992).","journal-title":"Muscle Nerve"},{"key":"67601_CR15","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1136\/pgmj.2005.036137","volume":"82","author":"V Bansal","year":"2006","unstructured":"Bansal, V., Kalita, J. & Misra, U. K. Diabetic neuropathy. Postgrad. Med. J. 82, 95\u2013100. https:\/\/doi.org\/10.1136\/pgmj.2005.036137 (2006).","journal-title":"Postgrad. Med. J."},{"key":"67601_CR16","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/j.1365-2249.2010.04240.x","volume":"162","author":"MF Belotto","year":"2010","unstructured":"Belotto, M. F. et al. Moderate exercise improves leucocyte function and decreases inflammation in diabetes. Clin. Exp. Immunol. 162, 237\u2013243. https:\/\/doi.org\/10.1111\/j.1365-2249.2010.04240.x (2010).","journal-title":"Clin. Exp. Immunol."},{"key":"67601_CR17","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/j.jpain.2017.01.006","volume":"18","author":"MH Pitcher","year":"2017","unstructured":"Pitcher, M. H., Tarum, F., Rauf, I. Z., Low, L. A. & Bushnell, C. Modest amounts of voluntary exercise reduce pain- and stress-related outcomes in a rat model of persistent hind limb inflammation. J. Pain 18, 687\u2013701. https:\/\/doi.org\/10.1016\/j.jpain.2017.01.006 (2017).","journal-title":"J. Pain"},{"key":"67601_CR18","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.mvr.2013.05.004","volume":"89","author":"YK Jan","year":"2013","unstructured":"Jan, Y. K., Shen, S., Foreman, R. D. & Ennis, W. J. Skin blood flow response to locally applied mechanical and thermal stresses in the diabetic foot. Microvasc. Res. 89, 40\u201346. https:\/\/doi.org\/10.1016\/j.mvr.2013.05.004 (2013).","journal-title":"Microvasc. Res."},{"key":"67601_CR19","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1016\/j.pain.2014.03.003","volume":"155","author":"M Leinders","year":"2014","unstructured":"Leinders, M. et al. Differential distribution of PI3K isoforms in spinal cord and dorsal root ganglia: Potential roles in acute inflammatory pain. Pain 155, 1150\u20131160. https:\/\/doi.org\/10.1016\/j.pain.2014.03.003 (2014).","journal-title":"Pain"},{"key":"67601_CR20","doi-asserted-by":"publisher","first-page":"153","DOI":"10.7150\/ijms.20501","volume":"15","author":"H Ren","year":"2018","unstructured":"Ren, H., Jin, H., Jia, Z., Ji, N. & Luo, F. Pulsed radiofrequency applied to the sciatic nerve improves neuropathic pain by down-regulating the expression of calcitonin gene-related peptide in the dorsal root ganglion. Int. J. Med. Sci. 15, 153\u2013160. https:\/\/doi.org\/10.7150\/ijms.20501 (2018).","journal-title":"Int. J. Med. Sci."},{"key":"67601_CR21","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1093\/brain\/awu007","volume":"137","author":"L Qu","year":"2014","unstructured":"Qu, L. et al. Enhanced excitability of MRGPRA3- and MRGPRD-positive nociceptors in a model of inflammatory itch and pain. Brain 137, 1039\u20131050. https:\/\/doi.org\/10.1093\/brain\/awu007 (2014).","journal-title":"Brain"},{"key":"67601_CR22","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.pain.2009.11.011","volume":"148","author":"F Wang","year":"2010","unstructured":"Wang, F. et al. Spinal macrophage migration inhibitory factor contributes to the pathogenesis of inflammatory hyperalgesia in rats. Pain 148, 275\u2013283. https:\/\/doi.org\/10.1016\/j.pain.2009.11.011 (2010).","journal-title":"Pain"},{"key":"67601_CR23","doi-asserted-by":"publisher","first-page":"174480691877548","DOI":"10.1177\/1744806918775482","volume":"14","author":"SU Noh","year":"2018","unstructured":"Noh, S. U., Lee, W. Y., Kim, W. S., Lee, Y. T. & Yoon, K. J. Expression of macrophage migration inhibitory factor in footpad skin lesions with diabetic neuropathy. Mol. Pain. 14, 1744806918775482. https:\/\/doi.org\/10.1177\/1744806918775482 (2018).","journal-title":"Mol. Pain."},{"key":"67601_CR24","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1007\/s10753-014-9934-x","volume":"37","author":"Z Wang","year":"2014","unstructured":"Wang, Z. et al. Inhibition of macrophage migration inhibitory factor reduces diabetic nephropathy in type II diabetes mice. Inflammation 37, 2020\u20132029. https:\/\/doi.org\/10.1007\/s10753-014-9934-x (2014).","journal-title":"Inflammation"},{"key":"67601_CR25","doi-asserted-by":"publisher","first-page":"5399","DOI":"10.4049\/jimmunol.179.8.5399","volume":"179","author":"T Atsumi","year":"2007","unstructured":"Atsumi, T. et al. The proinflammatory cytokine macrophage migration inhibitory factor regulates glucose metabolism during systemic inflammation. J. Immunol. 179, 5399\u20135406. https:\/\/doi.org\/10.4049\/jimmunol.179.8.5399 (2007).","journal-title":"J. Immunol."},{"key":"67601_CR26","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/377068a0","volume":"377","author":"T Calandra","year":"1995","unstructured":"Calandra, T. et al. MIF as a glucocorticoid-induced modulator of cytokine production. Nature 377, 68\u201371. https:\/\/doi.org\/10.1038\/377068a0 (1995).","journal-title":"Nature"},{"key":"67601_CR27","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1615\/CritRevImmunol.v37.i2-6.90","volume":"37","author":"T Calandra","year":"2017","unstructured":"Calandra, T. & Bucala, R. Macrophage migration inhibitory factor (MIF): A glucocorticoid counter-regulator within the immune system. Crit. Rev. Immunol. 37, 359\u2013370. https:\/\/doi.org\/10.1615\/CritRevImmunol.v37.i2-6.90 (2017).","journal-title":"Crit. Rev. Immunol."},{"key":"67601_CR28","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.smim.2014.03.004","volume":"26","author":"JK Lerch","year":"2014","unstructured":"Lerch, J. K., Puga, D. A., Bloom, O. & Popovich, P. G. Glucocorticoids and macrophage migration inhibitory factor (MIF) are neuroendocrine modulators of inflammation and neuropathic pain after spinal cord injury. Semin Immunol. 26, 409\u2013414. https:\/\/doi.org\/10.1016\/j.smim.2014.03.004 (2014).","journal-title":"Semin Immunol."},{"key":"67601_CR29","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1902\/jop.2008.080246","volume":"79","author":"GL King","year":"2008","unstructured":"King, G. L. The role of inflammatory cytokines in diabetes and its complications. J. Periodontol. 79, 1527\u20131534. https:\/\/doi.org\/10.1902\/jop.2008.080246 (2008).","journal-title":"J. Periodontol."},{"key":"67601_CR30","doi-asserted-by":"publisher","first-page":"170","DOI":"10.3389\/fendo.2012.00170","volume":"3","author":"DV Nguyen","year":"2012","unstructured":"Nguyen, D. V., Shaw, L. C. & Grant, M. B. Inflammation in the pathogenesis of microvascular complications in diabetes. Front. Endocrinol. 3, 170. https:\/\/doi.org\/10.3389\/fendo.2012.00170 (2012).","journal-title":"Front. Endocrinol."},{"key":"67601_CR31","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.2337\/diabetes.54.6.1615","volume":"54","author":"M Brownlee","year":"2005","unstructured":"Brownlee, M. The pathobiology of diabetic complications: A unifying mechanism. Diabetes 54, 1615\u20131625 (2005).","journal-title":"Diabetes"},{"key":"67601_CR32","doi-asserted-by":"publisher","first-page":"294","DOI":"10.2174\/157339910793360851","volume":"6","author":"K Kaul","year":"2010","unstructured":"Kaul, K., Hodgkinson, A., Tarr, J. M., Kohner, E. M. & Chibber, R. Is inflammation a common retinal\u2013renal\u2013nerve pathogenic link in diabetes?. Curr. Diabetes Rev. 6, 294\u2013303 (2010).","journal-title":"Curr. Diabetes Rev."},{"key":"67601_CR33","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.expneurol.2015.03.006","volume":"267","author":"H Yoon","year":"2015","unstructured":"Yoon, H., Thakur, V., Isham, D., Fayad, M. & Chattopadhyay, M. Moderate exercise training attenuates inflammatory mediators in DRG of Type 1 diabetic rats. Exp. Neurol. 267, 107\u2013114. https:\/\/doi.org\/10.1016\/j.expneurol.2015.03.006 (2015).","journal-title":"Exp. Neurol."},{"key":"67601_CR34","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1177\/1559827607300283","volume":"1","author":"MG Flynn","year":"2007","unstructured":"Flynn, M. G., McFarlin, B. K. & Markofski, M. M. The anti-inflammatory actions of exercise training. Am. J. Lifestyle Med. 1, 220\u2013235. https:\/\/doi.org\/10.1177\/1559827607300283 (2007).","journal-title":"Am. J. Lifestyle Med."},{"key":"67601_CR35","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1111\/j.1365-2249.2006.03229.x","volume":"146","author":"E Hatanaka","year":"2006","unstructured":"Hatanaka, E., Monteagudo, P. T., Marrocos, M. S. & Campa, A. Neutrophils and monocytes as potentially important sources of proinflammatory cytokines in diabetes. Clin. Exp. Immunol. 146, 443\u2013447. https:\/\/doi.org\/10.1111\/j.1365-2249.2006.03229.x (2006).","journal-title":"Clin. Exp. Immunol."},{"key":"67601_CR36","doi-asserted-by":"publisher","first-page":"2220","DOI":"10.2337\/dc11-1108","volume":"34","author":"CA Abbott","year":"2011","unstructured":"Abbott, C. A., Malik, R. A., van Ross, E. R., Kulkarni, J. & Boulton, A. J. Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the UK. Diabetes Care 34, 2220\u20132224. https:\/\/doi.org\/10.2337\/dc11-1108 (2011).","journal-title":"Diabetes Care"},{"key":"67601_CR37","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/bs.irn.2016.03.005","volume":"127","author":"SM Todorovic","year":"2016","unstructured":"Todorovic, S. M. Painful diabetic neuropathy: Prevention or suppression?. Int. Rev. Neurobiol. 127, 211\u2013225. https:\/\/doi.org\/10.1016\/bs.irn.2016.03.005 (2016).","journal-title":"Int. Rev. Neurobiol."},{"key":"67601_CR38","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1111\/j.1529-8027.2010.00271.x","volume":"15","author":"G Lauria","year":"2010","unstructured":"Lauria, G. et al. Intraepidermal nerve fiber density at the distal leg: A worldwide normative reference study. J. Peripheral Nervous Syst. 15, 202\u2013207. https:\/\/doi.org\/10.1111\/j.1529-8027.2010.00271.x (2010).","journal-title":"J. Peripheral Nervous Syst."},{"key":"67601_CR39","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1007\/s00415-009-5065-y","volume":"256","author":"M Nebuchennykh","year":"2009","unstructured":"Nebuchennykh, M., Loseth, S., Lindal, S. & Mellgren, S. I. The value of skin biopsy with recording of intraepidermal nerve fiber density and quantitative sensory testing in the assessment of small fiber involvement in patients with different causes of polyneuropathy. J. Neurol. 256, 1067\u20131075. https:\/\/doi.org\/10.1007\/s00415-009-5065-y (2009).","journal-title":"J. Neurol."},{"key":"67601_CR40","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13098-016-0146-4","volume":"8","author":"B Timar","year":"2016","unstructured":"Timar, B. et al. The usefulness of quantifying intraepidermal nerve fibers density in the diagnostic of diabetic peripheral neuropathy: A cross-sectional study. Diabetol. Metab. Syndr. 8, 31. https:\/\/doi.org\/10.1186\/s13098-016-0146-4 (2016).","journal-title":"Diabetol. Metab. Syndr."},{"key":"67601_CR41","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.jpain.2009.06.012","volume":"10","author":"A Latremoliere","year":"2009","unstructured":"Latremoliere, A. & Woolf, C. J. Central sensitization: A generator of pain hypersensitivity by central neural plasticity. J. Pain. 10, 895\u2013926. https:\/\/doi.org\/10.1016\/j.jpain.2009.06.012 (2009).","journal-title":"J. Pain."},{"key":"67601_CR42","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1016\/j.pain.2010.09.030","volume":"152","author":"CJ Woolf","year":"2011","unstructured":"Woolf, C. J. Central sensitization: Implications for the diagnosis and treatment of pain. Pain 152, S2-15. https:\/\/doi.org\/10.1016\/j.pain.2010.09.030 (2011).","journal-title":"Pain"},{"key":"67601_CR43","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1007\/s11916-017-0629-5","volume":"21","author":"K Meacham","year":"2017","unstructured":"Meacham, K., Shepherd, A., Mohapatra, D. P. & Haroutounian, S. Neuropathic pain: Central vs. peripheral mechanisms. Curr. Pain. Headache Rep. 21, 28. https:\/\/doi.org\/10.1007\/s11916-017-0629-5 (2017).","journal-title":"Curr. Pain. Headache Rep."},{"key":"67601_CR44","doi-asserted-by":"publisher","first-page":"615","DOI":"10.2147\/jpr.S154437","volume":"11","author":"R Zhou","year":"2018","unstructured":"Zhou, R. et al. Activation of spinal dorsal horn P2Y13 receptors can promote the expression of IL-1beta and IL-6 in rats with diabetic neuropathic pain. J. Pain Res. 11, 615\u2013628. https:\/\/doi.org\/10.2147\/jpr.S154437 (2018).","journal-title":"J. Pain Res."},{"key":"67601_CR45","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"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67601-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67601-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67601-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T12:30:30Z","timestamp":1670329830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67601-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,26]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["67601"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-67601-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,26]]},"assertion":[{"value":"13 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2020","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":"10498"}}