{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:47:33Z","timestamp":1792799253357,"version":"4.5.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Brain"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The aim of this study was to explore the relationships among gut microbiota disturbances and serum and spinal cord metabolic disorders in neuropathic pain. 16S rDNA amplicon sequencing and serum and spinal cord metabolomics were used to identify alterations in the microbiota and metabolite profiles in the sham rats and the chronic constriction injury (CCI) model rats. Correlations between the abundances of gut microbiota components at the genus level, the levels of serum metabolites, and pain-related behavioural parameters were analysed. Ingenuity pathway analysis (IPA) was applied to analyse the interaction networks of the differentially expressed serum metabolites. First, we found that the composition of the gut microbiota was different between rats with CCI-induced neuropathic pain and sham controls. At the genus level, the abundances of\n                    <jats:italic>Helicobacter<\/jats:italic>\n                    ,\n                    <jats:italic>Phascolarctobacterium<\/jats:italic>\n                    ,\n                    <jats:italic>Christensenella<\/jats:italic>\n                    ,\n                    <jats:italic>Blautia<\/jats:italic>\n                    ,\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    ,\n                    <jats:italic>Rothia<\/jats:italic>\n                    and\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    were significantly increased, whereas the abundances of\n                    <jats:italic>Ignatzschineria<\/jats:italic>\n                    ,\n                    <jats:italic>Butyricimonas<\/jats:italic>\n                    ,\n                    <jats:italic>Escherichia<\/jats:italic>\n                    ,\n                    <jats:italic>AF12<\/jats:italic>\n                    , and\n                    <jats:italic>Corynebacterium<\/jats:italic>\n                    were significantly decreased. Additionally, 72 significantly differentially expressed serum metabolites and 17 significantly differentially expressed spinal cord metabolites were identified between the CCI rats and the sham rats. Finally, correlation analysis showed that changes in the gut microbiota was significantly correlated with changes in serum metabolite levels, suggesting that dysbiosis of the gut microbiota is an important factor in modulating metabolic disturbances in the context of neuropathic pain. In conclusion, our research provides a novel perspective on the potential roles of the gut microbiota and related metabolites in neuropathic pain.\n                  <\/jats:p>","DOI":"10.1186\/s13041-021-00765-y","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T04:03:37Z","timestamp":1615262617000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain"],"prefix":"10.1186","volume":"14","author":[{"given":"Peng","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-na","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeng-jie","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-bing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"issue":"10","key":"765_CR1","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.1016\/j.pain.2011.06.017","volume":"152","author":"TS Jensen","year":"2011","unstructured":"Jensen TS, Baron R, Haanpaa M, Kalso E, Loeser JD, Rice AS, Treede RA. A new definition of neuropathic pain. Pain. 2011;152(10):2204\u20135. https:\/\/doi.org\/10.1016\/j.pain.2011.06.017.","journal-title":"Pain"},{"issue":"4","key":"765_CR2","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.pain.2013.11.013","volume":"155","author":"O van Hecke","year":"2014","unstructured":"van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014;155(4):654\u201362. https:\/\/doi.org\/10.1016\/j.pain.2013.11.013.","journal-title":"Pain"},{"issue":"1","key":"765_CR3","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1097\/j.pain.0000000000001365","volume":"160","author":"J Scholz","year":"2019","unstructured":"Scholz J, Finnerup NB, Attal N, Aziz Q, Baron R, Bennett MI, Benoliel R, Cohen M, Cruccu G, Davis KD, et al. The IASP classification of chronic pain for ICD-11: chronic neuropathic pain. Pain. 2019;160(1):53\u20139. https:\/\/doi.org\/10.1097\/j.pain.0000000000001365.","journal-title":"Pain"},{"issue":"5","key":"765_CR4","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1097\/01.j.pain.0000460356.94374.a1","volume":"156","author":"PR Kamerman","year":"2015","unstructured":"Kamerman PR, Wadley AL, Davis KD, Hietaharju A, Jain P, Kopf A, Meyer AC, Raja SN, Rice AC, Smith BH, et al. World Health Organization essential medicines lists: where are the drugs to treat neuropathic pain? Pain. 2015;156(5):793\u20137. https:\/\/doi.org\/10.1097\/01.j.pain.0000460356.94374.a1.","journal-title":"Pain"},{"issue":"2","key":"765_CR5","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, Haanp\u00e4\u00e4 M, Hansson P, Jensen TS, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162\u201373. https:\/\/doi.org\/10.1016\/S1474-4422(14)70251-0.","journal-title":"Lancet Neurol."},{"issue":"8","key":"765_CR6","doi-asserted-by":"publisher","first-page":"e1002533","DOI":"10.1371\/journal.pbio.1002533","volume":"14","author":"R Sender","year":"2016","unstructured":"Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. Plos Biol. 2016;14(8):e1002533. https:\/\/doi.org\/10.1371\/journal.pbio.1002533.","journal-title":"Plos Biol."},{"issue":"3","key":"765_CR7","first-page":"127","volume":"57","author":"R Catanzaro","year":"2015","unstructured":"Catanzaro R, Anzalone M, Calabrese F, Milazzo M, Capuana M, Italia A, Occhipinti S, Marotta F. The gut microbiota and its correlations with the central nervous system disorders. Panminerva Med. 2015;57(3):127\u201343.","journal-title":"Panminerva Med"},{"key":"765_CR8","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fendo.2020.00025","volume":"11","author":"YP Silva","year":"2020","unstructured":"Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol (Lausanne). 2020;11:25. https:\/\/doi.org\/10.3389\/fendo.2020.00025.","journal-title":"Front Endocrinol (Lausanne)."},{"key":"765_CR9","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1016\/j.bbi.2020.01.009","volume":"87","author":"W Zheng","year":"2020","unstructured":"Zheng W, He R, Yan Z, Huang Y, Huang W, Cai Z, Su Y, Liu S, Deng Y, Wang Q, et al. Regulation of immune-driven pathogenesis in Parkinson\u2019s disease by gut microbiota. Brain Behav Immun. 2020;87:890\u20137. https:\/\/doi.org\/10.1016\/j.bbi.2020.01.009.","journal-title":"Brain Behav Immun."},{"issue":"4","key":"765_CR10","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1111\/jam","volume":"127","author":"M Bostanciklioglu","year":"2019","unstructured":"Bostanciklioglu M. The role of gut microbiota in pathogenesis of Alzheimer\u2019s disease. J Appl Microbiol. 2019;127(4):954\u201367. https:\/\/doi.org\/10.1111\/jam.","journal-title":"J Appl Microbiol."},{"key":"765_CR11","doi-asserted-by":"publisher","first-page":"598","DOI":"10.3389\/fneur.2020.00598","volume":"11","author":"D Battaglini","year":"2020","unstructured":"Battaglini D, Pimentel-Coelho PM, Robba C, Dos SC, Cruz FF, Pelosi P, Rocco PRM. Gut microbiota in acute ischemic stroke: from pathophysiology to therapeutic implications. Front Neurol. 2020;11:598. https:\/\/doi.org\/10.3389\/fneur.2020.00598.","journal-title":"Front Neurol."},{"key":"765_CR12","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.3389\/fimmu.2020.01390","volume":"11","author":"M Saresella","year":"2020","unstructured":"Saresella M, Marventano I, Barone M, La Rosa F, Piancone F, Mendozzi L, d\u2019Arma A, Rossi V, Pugnetti L, Roda G, et al. Alterations in circulating fatty acid are associated with gut microbiota dysbiosis and inflammation in multiple sclerosis. Front Immunol. 2020;11:1390. https:\/\/doi.org\/10.3389\/fimmu.2020.01390.","journal-title":"Front Immunol."},{"key":"765_CR13","doi-asserted-by":"publisher","first-page":"704","DOI":"10.3389\/fimmu.2020.00704","volume":"11","author":"T Jogia","year":"2020","unstructured":"Jogia T, Ruitenberg MJ. Traumatic spinal cord injury and the gut microbiota: current insights and future challenges. Front Immunol. 2020;11:704. https:\/\/doi.org\/10.3389\/fimmu.2020.00704.","journal-title":"Front Immunol."},{"issue":"1","key":"765_CR14","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s10194-020-01170-x","volume":"21","author":"B Lin","year":"2020","unstructured":"Lin B, Wang Y, Zhang P, Yuan Y, Zhang Y, Chen G. Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy. J Headache Pain. 2020;21(1):103. https:\/\/doi.org\/10.1186\/s10194-020-01170-x.","journal-title":"J Headache Pain."},{"key":"765_CR15","doi-asserted-by":"publisher","first-page":"113147","DOI":"10.1016\/j.physbeh.2020.113147","volume":"227","author":"L Voderova","year":"2020","unstructured":"Voderova L, Sandera S, Drobil T, Plevova B, Vaculin S. Skin temperature contribution to the decrease in withdrawal latency following chronic constriction injury. Physiol Behav. 2020;227:113147. https:\/\/doi.org\/10.1016\/j.physbeh.2020.113147.","journal-title":"Physiol Behav."},{"issue":"1","key":"765_CR16","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/0304-3959(88)90209-6","volume":"33","author":"GJ Bennett","year":"1988","unstructured":"Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33(1):87\u2013107. https:\/\/doi.org\/10.1016\/0304-3959(88)90209-6.","journal-title":"Pain"},{"issue":"5","key":"765_CR17","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1128\/mBio.01340-15","volume":"6","author":"AC Gerstein","year":"2015","unstructured":"Gerstein AC, Fu MS, Mukaremera L, Li Z, Ormerod KL, Fraser JA, Berman J, Nielsen K, et al. Polyploid titan cells produce haploid and aneuploid progeny to promote stress adaptation. MBIO. 2015;6(5):1315\u201340. https:\/\/doi.org\/10.1128\/mBio.01340-15.","journal-title":"MBIO."},{"issue":"11","key":"765_CR18","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.1002\/ijc.32007","volume":"144","author":"J Feng","year":"2019","unstructured":"Feng J, Zhao F, Sun J, Lin B, Zhao L, Liu Y, Jin Y, Li S, Li A, Wei Y. Alterations in the gut microbiota and metabolite profiles of thyroid carcinoma patients. Int J Cancer. 2019;144(11):2728\u201345. https:\/\/doi.org\/10.1002\/ijc.32007.","journal-title":"Int J Cancer."},{"issue":"1","key":"765_CR19","doi-asserted-by":"publisher","first-page":"20324","DOI":"10.1038\/s41598-019-56832-x","volume":"9","author":"C Ramakrishna","year":"2019","unstructured":"Ramakrishna C, Corleto J, Ruegger PM, Logan GD, Peacock BB, Mendonca S, Yamaki S, Adamson T, Ermel R, McKemy D, et al. Dominant role of the gut microbiota in chemotherapy induced neuropathic pain. Sci Rep. 2019;9(1):20324. https:\/\/doi.org\/10.1038\/s41598-019-56832-x.","journal-title":"Sci Rep."},{"key":"765_CR20","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000005155","author":"W Ding","year":"2020","unstructured":"Ding W, You Z, Chen Q, Yang L, Doheny J, Zhou X, Li N, Wang S, Hu K, Chen L, et al. Gut microbiota influences neuropathic pain through modulating proinflammatory and anti-inflammatory T cells. Anesth Analg. 2020. https:\/\/doi.org\/10.1213\/ANE.0000000000005155.","journal-title":"Anesth Analg."},{"issue":"4","key":"765_CR21","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1007\/s12975-019-00760-5","volume":"11","author":"MJ Park","year":"2020","unstructured":"Park MJ, Pilla R, Panta A, Pandey S, Sarawichitr B, Suchodolski J, Sohrabji F. Reproductive senescence and ischemic stroke remodel the gut microbiome and modulate the effects of estrogen treatment in female rats. Transl Stroke Res. 2020;11(4):812\u201330. https:\/\/doi.org\/10.1007\/s12975-019-00760-5.","journal-title":"Transl Stroke Res."},{"issue":"3","key":"765_CR22","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.apsb.2019.07.001","volume":"10","author":"X Yang","year":"2020","unstructured":"Yang X, Yu D, Xue L, Li H, Du J. Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice. Acta Pharm Sin B. 2020;10(3):475\u201387. https:\/\/doi.org\/10.1016\/j.apsb.2019.07.001.","journal-title":"Acta Pharm Sin B."},{"issue":"12","key":"765_CR23","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/j.molmet.2016.10.003","volume":"5","author":"C Benedict","year":"2016","unstructured":"Benedict C, Vogel H, Jonas W, Woting A, Blaut M, Schurmann A, Cedernaes J. Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals. Mol Metab. 2016;5(12):1175\u201386. https:\/\/doi.org\/10.1016\/j.molmet.2016.10.003.","journal-title":"Mol Metab."},{"key":"765_CR24","doi-asserted-by":"publisher","first-page":"541","DOI":"10.3389\/fpsyt.2020.00541","volume":"11","author":"ZA Barandouzi","year":"2020","unstructured":"Barandouzi ZA, Starkweather AR, Henderson WA, Gyamfi A, Cong XS. Altered composition of gut microbiota in depression: a systematic review. Front Psychiatry. 2020;11:541. https:\/\/doi.org\/10.3389\/fpsyt.2020.00541.","journal-title":"Front Psychiatry."},{"issue":"3","key":"765_CR25","doi-asserted-by":"publisher","first-page":"792","DOI":"10.3390\/nu12030792","volume":"12","author":"L Iglesias-Vazquez","year":"2020","unstructured":"Iglesias-Vazquez L, Van Ginkel RG, Arija V, Canals J. Composition of gut microbiota in children with autism spectrum disorder: a systematic review and meta-analysis. Nutrients. 2020;12(3):792. https:\/\/doi.org\/10.3390\/nu12030792.","journal-title":"Nutrients."},{"issue":"1","key":"765_CR26","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1186\/s13023-020-01612-4","volume":"15","author":"V Kuznetsova","year":"2020","unstructured":"Kuznetsova V, Tyakht A, Akhmadishina L, Odintsova V, Klimenko N, Kostryukova E, Vakhitova M, Grigoryeva T, Malanin S, Vladimirtsev V, et al. Gut microbiome signature of Viliuisk encephalomyelitis in Yakuts includes an increase in microbes linked to lean body mass and eating behaviour. Orphanet J Rare Dis. 2020;15(1):327. https:\/\/doi.org\/10.1186\/s13023-020-01612-4.","journal-title":"Orphanet J Rare Dis."},{"issue":"3","key":"765_CR27","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/s12020-018-1605-5","volume":"61","author":"A Pascale","year":"2018","unstructured":"Pascale A, Marchesi N, Marelli C, Coppola A, Luzi L, Govoni S, Giustina A, Gazzaruso C. Microbiota and metabolic diseases. Endocrine. 2018;61(3):357\u201371. https:\/\/doi.org\/10.1007\/s12020-018-1605-5.","journal-title":"Endocrine"},{"issue":"sup1","key":"765_CR28","doi-asserted-by":"publisher","first-page":"S130","DOI":"10.1080\/10408398.2018.1542587","volume":"59","author":"X Fu","year":"2019","unstructured":"Fu X, Liu Z, Zhu C, Mou H, Kong Q. Nondigestible carbohydrates, butyrate, and butyrate-producing bacteria. Crit Rev Food Sci Nutr. 2019;59(sup1):S130\u201352. https:\/\/doi.org\/10.1080\/10408398.2018.1542587.","journal-title":"Crit Rev Food Sci Nutr."},{"key":"765_CR29","doi-asserted-by":"publisher","first-page":"12015","DOI":"10.1038\/ncomms12015","volume":"7","author":"S Jangi","year":"2016","unstructured":"Jangi S, Gandhi R, Cox LM, Li N, von Glehn F, Yan R, Patel B, Mazzola MA, Liu S, Glanz B, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016;7:12015. https:\/\/doi.org\/10.1038\/ncomms12015.","journal-title":"Nat Commun."},{"key":"765_CR30","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.bbi.2020.08.015","volume":"89","author":"JH Jang","year":"2020","unstructured":"Jang JH, Yeom MJ, Ahn S, Oh JY, Ji S, Kim TH, Park HJ. Acupuncture inhibits neuroinflammation and gut microbial dysbiosis in a mouse model of Parkinson\u2019s disease. Brain Behav Immun. 2020;89:641\u201355. https:\/\/doi.org\/10.1016\/j.bbi.2020.08.015.","journal-title":"Brain Behav Immun."},{"issue":"12","key":"765_CR31","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1038\/s41398-017-0031-4","volume":"7","author":"C Yang","year":"2017","unstructured":"Yang C, Qu Y, Fujita Y, Ren Q, Ma M, Dong C, Hashimoto K. Possible role of the gut microbiota-brain axis in the antidepressant effects of (R)-ketamine in a social defeat stress model. Transl Psychiatry. 2017;7(12):1294. https:\/\/doi.org\/10.1038\/s41398-017-0031-4.","journal-title":"Transl Psychiatry."},{"key":"765_CR32","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1146\/annurev-nutr-071816-064916","volume":"37","author":"JC Newman","year":"2017","unstructured":"Newman JC, Verdin E. Beta-hydroxybutyrate: a signaling metabolite. Annu Rev Nutr. 2017;37:51\u201376. https:\/\/doi.org\/10.1146\/annurev-nutr-071816-064916.","journal-title":"Annu Rev Nutr."},{"issue":"4","key":"765_CR33","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/s12276-020-0415-z","volume":"52","author":"YM Han","year":"2020","unstructured":"Han YM, Ramprasath T, Zou MH. beta-hydroxybutyrate and its metabolic effects on age-associated pathology. Exp Mol Med. 2020;52(4):548\u201355. https:\/\/doi.org\/10.1038\/s12276-020-0415-z.","journal-title":"Exp Mol Med."},{"issue":"7","key":"765_CR34","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1016\/j.cell.2018.06.051","volume":"173","author":"CA Olson","year":"2018","unstructured":"Olson CA, Vuong HE, Yano JM, Liang QY, Nusbaum DJ, Hsiao EY. The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell. 2018;173(7):1728\u201341. https:\/\/doi.org\/10.1016\/j.cell.2018.06.051.","journal-title":"Cell"},{"key":"765_CR35","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.nut.2018.10.003","volume":"60","author":"GM Broom","year":"2019","unstructured":"Broom GM, Shaw IC, Rucklidge JJ. The ketogenic diet as a potential treatment and prevention strategy for Alzheimer\u2019s disease. Nutrition. 2019;60:118\u201321. https:\/\/doi.org\/10.1016\/j.nut.2018.10.003.","journal-title":"Nutrition"},{"issue":"8","key":"765_CR36","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1002\/mds.27390","volume":"33","author":"M Phillips","year":"2018","unstructured":"Phillips M, Murtagh D, Gilbertson LJ, Asztely F, Lynch C. Low-fat versus ketogenic diet in Parkinson\u2019s disease: a pilot randomized controlled trial. Mov Disord. 2018;33(8):1306\u201314. https:\/\/doi.org\/10.1002\/mds.27390.","journal-title":"Mov Disord."},{"issue":"4","key":"765_CR37","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1016\/j.jstrokecerebrovasdis","volume":"28","author":"S Shaafi","year":"2019","unstructured":"Shaafi S, Sharifi-Bonab M, Ghaemian N, Mokhtarkhani M, Akbari H. Early motor-behavioral outcome of ischemic stroke with ketogenic diet preconditioning: interventional animal study. J Stroke Cerebrovasc Dis. 2019;28(4):1032\u20139. https:\/\/doi.org\/10.1016\/j.jstrokecerebrovasdis.","journal-title":"J Stroke Cerebrovasc Dis."},{"issue":"12","key":"765_CR38","doi-asserted-by":"publisher","first-page":"e8349","DOI":"10.1371\/journal.pone.0008349","volume":"4","author":"DN Ruskin","year":"2009","unstructured":"Ruskin DN, Kawamura M, Masino SA. Reduced pain and inflammation in juvenile and adult rats fed a ketogenic diet. PLoS ONE. 2009;4(12):e8349. https:\/\/doi.org\/10.1371\/journal.pone.0008349.","journal-title":"PLoS ONE"},{"issue":"13","key":"765_CR39","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1111\/bph.13788","volume":"174","author":"J Qian","year":"2017","unstructured":"Qian J, Zhu W, Lu M, Ni B, Yang J. D-beta-hydroxybutyrate promotes functional recovery and relieves pain hypersensitivity in mice with spinal cord injury. Br J Pharmacol. 2017;174(13):1961\u201371. https:\/\/doi.org\/10.1111\/bph.13788.","journal-title":"Br J Pharmacol."},{"key":"765_CR40","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.brainres.2009.02.074","volume":"1268","author":"Y Suzuki","year":"2009","unstructured":"Suzuki Y, Takahashi H, Fukuda M, Hino H, Kobayashi K, Tanaka J, Ishii E. Beta-hydroxybutyrate alters GABA-transaminase activity in cultured astrocytes. Brain Res. 2009;1268:17\u201323. https:\/\/doi.org\/10.1016\/j.brainres.2009.02.074.","journal-title":"Brain Res."},{"key":"765_CR41","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1146\/annurev.nutr.27.061406.093722","volume":"27","author":"M Yudkoff","year":"2007","unstructured":"Yudkoff M, Daikhin Y, Melo TM, Nissim I, Sonnewald U, Nissim I. The ketogenic diet and brain metabolism of amino acids: relationship to the anticonvulsant effect. Annu Rev Nutr. 2007;27:415\u201330. https:\/\/doi.org\/10.1146\/annurev.nutr.27.061406.093722.","journal-title":"Annu Rev Nutr."},{"issue":"Pt 6","key":"765_CR42","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1099\/ijs.0.018622-0","volume":"61","author":"AK Gupta","year":"2011","unstructured":"Gupta AK, Dharne MS, Rangrez AY, Verma P, Ghate HV, Rohde M, Patole MS, Shouche YS. Ignatzschineria indica sp. nov. and Ignatzschineria ureiclastica sp. nov., isolated from adult flesh flies (Diptera: Sarcophagidae). Int J Syst Evol Microbiol. 2011;61(Pt 6):1360\u20139. https:\/\/doi.org\/10.1099\/ijs.0.018622-0.","journal-title":"Int J Syst Evol Microbiol."},{"issue":"3","key":"765_CR43","doi-asserted-by":"publisher","first-page":"e5043","DOI":"10.1099\/jmmcr.0.005043","volume":"3","author":"E Heddema","year":"2016","unstructured":"Heddema E, Janssen F, van Westreenen H. A case of Ignatzschineria bacteraemia in an unconscious man from the Netherlands. JMM Case Rep. 2016;3(3):e5043. https:\/\/doi.org\/10.1099\/jmmcr.0.005043.","journal-title":"JMM Case Rep."},{"issue":"11","key":"765_CR44","doi-asserted-by":"publisher","first-page":"3627","DOI":"10.1099\/ijsem.0.003046","volume":"68","author":"CC Tsang","year":"2018","unstructured":"Tsang CC, Tang J, Fong J, Kinne J, Lee HH, Joseph M, Jose S, Schuster R, Tang Y, Sivakumar S, Chen J, et al. Ignatzschineria cameli sp. nov., isolated from necrotic foot tissue of dromedaries (Camelus dromedarius) and associated maggots (Wohlfahrtia species) in Dubai. Int J Syst Evol Microbiol. 2018;68(11):3627\u201334. https:\/\/doi.org\/10.1099\/ijsem.0.003046.","journal-title":"Int J Syst Evol Microbiol."},{"issue":"3","key":"765_CR45","doi-asserted-by":"publisher","first-page":"848","DOI":"10.3390\/nu12030848","volume":"12","author":"M Holecek","year":"2020","unstructured":"Holecek M. Histidine in health and disease: metabolism, physiological importance, and use as a supplement. Nutrients. 2020;12(3):848. https:\/\/doi.org\/10.3390\/nu12030848.","journal-title":"Nutrients."},{"issue":"3","key":"765_CR46","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1111\/bph.14696","volume":"177","author":"I Obara","year":"2020","unstructured":"Obara I, Telezhkin V, Alrashdi I, Chazot PL. Histamine, histamine receptors, and neuropathic pain relief. Br J Pharmacol. 2020;177(3):580\u201399. https:\/\/doi.org\/10.1111\/bph.14696.","journal-title":"Br J Pharmacol."},{"issue":"3","key":"765_CR47","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s12264-013-1316-0","volume":"29","author":"J Yu","year":"2013","unstructured":"Yu J, Lou GD, Yue JX, Tang YY, Hou WW, Shou WT, Ohtsu H, Zhang SH, Chen Z. Effects of histamine on spontaneous neuropathic pain induced by peripheral axotomy. Neurosci Bull. 2013;29(3):261\u20139. https:\/\/doi.org\/10.1007\/s12264-013-1316-0.","journal-title":"Neurosci Bull."},{"issue":"2","key":"765_CR48","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.rapm.2006.11.009","volume":"32","author":"L Huang","year":"2007","unstructured":"Huang L, Adachi N, Nagaro T, Liu K, Arai T. Histaminergic involvement in neuropathic pain produced by partial ligation of the sciatic nerve in rats. Reg Anesth Pain Med. 2007;32(2):124\u20139. https:\/\/doi.org\/10.1016\/j.rapm.2006.11.009.","journal-title":"Reg Anesth Pain Med."},{"issue":"1","key":"765_CR49","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/s12974-016-0637-0","volume":"13","author":"J Yu","year":"2016","unstructured":"Yu J, Tang YY, Wang RR, Lou GD, Hu TT, Hou WW, Yue JX, Ohtsu H, Shi LY, Zhang SH, et al. A critical time window for the analgesic effect of central histamine in the partial sciatic ligation model of neuropathic pain. J Neuroinflammation. 2016;13(1):163. https:\/\/doi.org\/10.1186\/s12974-016-0637-0.","journal-title":"J Neuroinflammation."},{"issue":"8","key":"765_CR50","doi-asserted-by":"publisher","first-page":"e4842","DOI":"10.1002\/bmc.4842","volume":"34","author":"T Recber","year":"2020","unstructured":"Recber T, Orgul G, Aydin E, Tanacan A, Nemutlu E, Kir S, Beksac MS. Metabolic infrastructure of pregnant women with methylenetetrahydrofolate reductase polymorphisms: a metabolomic analysis. Biomed Chromatosr. 2020;34(8):e4842. https:\/\/doi.org\/10.1002\/bmc.4842.","journal-title":"Biomed Chromatosr."},{"key":"765_CR51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2016.03.005","volume":"43","author":"D Ciavardelli","year":"2016","unstructured":"Ciavardelli D, Piras F, Consalvo A, Rossi C, Zucchelli M, Di Ilio C, Frazzini V, Caltagirone C, Spalletta G, Sensi S. Medium-chain plasma acylcarnitines, ketone levels, cognition, and gray matter volumes in healthy elderly, mildly cognitively impaired, or Alzheimer\u2019s disease subjects. Neurobiol Aging. 2016;43:1\u201312. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2016.03.005.","journal-title":"Neurobiol Aging."},{"issue":"5","key":"765_CR52","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.3390\/ijms20051220","volume":"20","author":"Y Xu","year":"2019","unstructured":"Xu Y, Han J, Dong J, Fan X, Cai Y, Li J, Wang T, Zhou J, Shang J. Metabolomics characterizes the effects and mechanisms of quercetin in nonalcoholic fatty liver disease development. Int J Mol Sci. 2019;20(5):1220. https:\/\/doi.org\/10.3390\/ijms20051220.","journal-title":"Int J Mol Sci."},{"issue":"18","key":"765_CR53","doi-asserted-by":"publisher","first-page":"5212","DOI":"10.3748\/wjg.v20.i18.5212","volume":"20","author":"J Budzynski","year":"2014","unstructured":"Budzynski J, Klopocka M. Brain-gut axis in the pathogenesis of Helicobacter pylori infection. World J Gastroenterol. 2014;20(18):5212\u201325. https:\/\/doi.org\/10.3748\/wjg.v20.i18.5212.","journal-title":"World J Gastroenterol."},{"key":"765_CR54","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2020.1738432","author":"M Doulberis","year":"2020","unstructured":"Doulberis M, Kotronis G, Gialamprinou D, Polyzos SA, Papaefthymiou A, Katsinelos P, Kountouras J. Alzheimer\u2019s disease and gastrointestinal microbiota; impact of Helicobacter pylori infection involvement. Int J Neurosci. 2020. https:\/\/doi.org\/10.1080\/00207454.2020.1738432.","journal-title":"Int J Neurosci."},{"key":"765_CR55","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.neuropharm.2015.06.003","volume":"97","author":"C Sagheddu","year":"2015","unstructured":"Sagheddu C, Aroni S, De Felice M, Lecca S, Luchicchi A, Melis M, Lisa Muntoni A, Romano R, Palazzo E, Guida F, et al. Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain. Neuropharmacology. 2015;97:383\u201393. https:\/\/doi.org\/10.1016\/j.neuropharm.2015.06.003.","journal-title":"Neuropharmacology"},{"key":"765_CR56","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1186\/1471-2474-15-409","volume":"15","author":"K Chakravarthy","year":"2014","unstructured":"Chakravarthy K, Faltus R, Robinson G, Sevilla R, Shin J, Zielstorff M, Byford A, Leccese E, Caniga M, Hseih SC, et al. Etanercept ameliorates inflammation and pain in a novel mono-arthritic multi-flare model of streptococcal cell wall induced arthritis. BMC Musculoskelet Disord. 2014;15:409. https:\/\/doi.org\/10.1186\/1471-2474-15-409.","journal-title":"BMC Musculoskelet Disord."},{"issue":"5","key":"765_CR57","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.bja.2019.07.026","volume":"123","author":"R Guo","year":"2019","unstructured":"Guo R, Chen LH, Xing C, Liu T. Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential. Br J Anaesth. 2019;123(5):637\u201354. https:\/\/doi.org\/10.1016\/j.bja.2019.07.026.","journal-title":"Br J Anaesth."}],"container-title":["Molecular Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13041-021-00765-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13041-021-00765-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13041-021-00765-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T04:10:32Z","timestamp":1615263032000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecularbrain.biomedcentral.com\/articles\/10.1186\/s13041-021-00765-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,9]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["765"],"URL":"https:\/\/doi.org\/10.1186\/s13041-021-00765-y","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-149088\/v1","asserted-by":"object"}]},"ISSN":["1756-6606"],"issn-type":[{"value":"1756-6606","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,9]]},"assertion":[{"value":"14 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was reviewed and approved by Animal Use and Ethics Committee, Affiliated Hospital of Guangzhou University of Chinese Medicine.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing financial interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"50"}}