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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Review Article

Potential Therapeutic Effects of Short-Chain Fatty Acids on Chronic Pain

Author(s): Yuanyuan Tang, Juan Du, Hongfeng Wu, Mengyao Wang, Sufang Liu* and Feng Tao*

Volume 22, Issue 2, 2024

Published on: 17 January, 2023

Page: [191 - 203] Pages: 13

DOI: 10.2174/1570159X20666220927092016

Price: $65

Abstract

The intestinal homeostasis maintained by the gut microbiome and relevant metabolites is essential for health, and its disturbance leads to various intestinal or extraintestinal diseases. Recent studies suggest that gut microbiome-derived metabolites short-chain fatty acids (SCFAs) are involved in different neurological disorders (such as chronic pain). SCFAs are produced by bacterial fermentation of dietary fibers in the gut and contribute to multiple host processes, including gastrointestinal regulation, cardiovascular modulation, and neuroendocrine-immune homeostasis. Although SCFAs have been implicated in the modulation of chronic pain, the detailed mechanisms that underlie such roles of SCFAs remain to be further investigated. In this review, we summarize currently available research data regarding SCFAs as a potential therapeutic target for chronic pain treatment and discuss several possible mechanisms by which SCFAs modulate chronic pain.

Keywords: short-chain fatty acids, chronic pain, gut microbiome, metabolites, gut- brain communication

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[1]
Zhou, F.; Wang, X.; Han, B.; Tang, X.; Liu, R.; Ji, Q.; Zhou, Z.; Zhang, L. Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization. Mol. Pain, 2021, 17.
[http://dx.doi.org/10.1177/1744806921996520] [PMID: 33626986]
[2]
Bonomo, R.R.; Cook, T.M.; Gavini, C.K.; White, C.R.; Jones, J.R.; Bovo, E.; Zima, A.V.; Brown, I.A.; Dugas, L.R.; Zakharian, E.; Aubert, G.; Alonzo, F., III; Calcutt, N.A.; Mansuy-Aubert, V. Fecal transplantation and butyrate improve neuropathic pain, modify immune cell profile, and gene expression in the PNS of obese mice. Proc. Natl. Acad. Sci. USA, 2020, 117(42), 26482-26493.
[http://dx.doi.org/10.1073/pnas.2006065117] [PMID: 33020290]
[3]
Zhang, J.; Song, L.; Wang, Y.; Liu, C.; Zhang, L.; Zhu, S.; Liu, S.; Duan, L. Beneficial effect of butyrate‐producing Lachnospiraceae on stress‐induced visceral hypersensitivity in rats. J. Gastroenterol. Hepatol., 2019, 34(8), 1368-1376.
[http://dx.doi.org/10.1111/jgh.14536] [PMID: 30402954]
[4]
O’ Mahony, S.M.; Dinan, T.G.; Cryan, J.F. The gut microbiota as a key regulator of visceral pain. Pain, 2017, 158(1), S19-S28.
[http://dx.doi.org/10.1097/j.pain.0000000000000779] [PMID: 27918315]
[5]
Vanhoutvin, S.A.L.W.; Troost, F.J.; Kilkens, T.O.C.; Lindsey, P.J.; Hamer, H.M.; Jonkers, D.M.A.E.; Venema, K.; Brummer, R-J.M. The effects of butyrate enemas on visceral perception in healthy volunteers. Neurogastroenterol. Motil., 2009, 21(9), 952-e76.
[http://dx.doi.org/10.1111/j.1365-2982.2009.01324.x] [PMID: 19460106]
[6]
Luczynski, P.; Tramullas, M.; Viola, M.; Shanahan, F.; Clarke, G.; O’Mahony, S.; Dinan, T.G.; Cryan, J.F. Microbiota regulates visceral pain in the mouse. eLife, 2017, 6, e25887.
[http://dx.doi.org/10.7554/eLife.25887] [PMID: 28629511]
[7]
Shen, S.; Lim, G.; You, Z.; Ding, W.; Huang, P.; Ran, C.; Doheny, J.; Caravan, P.; Tate, S.; Hu, K.; Kim, H.; McCabe, M.; Huang, B.; Xie, Z.; Kwon, D.; Chen, L.; Mao, J. Gut microbiota is critical for the induction of chemotherapy-induced pain. Nat. Neurosci., 2017, 20(9), 1213-1216.
[http://dx.doi.org/10.1038/nn.4606] [PMID: 28714953]
[8]
Tang, Y.; Liu, S.; Shu, H.; Yanagisawa, L.; Tao, F. Gut microbiota dysbiosis enhances migraine-like pain via TNFα upregulation. Mol. Neurobiol., 2020, 57(1), 461-468.
[http://dx.doi.org/10.1007/s12035-019-01721-7] [PMID: 31378003]
[9]
Crawford, J.; Liu, S.; Tao, F. Gut microbiota and migraine. Neurobiol. Pain, 2022, 11, 100090.
[http://dx.doi.org/10.1016/j.ynpai.2022.100090] [PMID: 35464185]
[10]
Minerbi, A.; Gonzalez, E.; Brereton, N.J.B.; Anjarkouchian, A.; Dewar, K.; Fitzcharles, M.A.; Chevalier, S.; Shir, Y. Altered microbiome composition in individuals with fibromyalgia. Pain, 2019, 160(11), 2589-2602.
[http://dx.doi.org/10.1097/j.pain.0000000000001640] [PMID: 31219947]
[11]
Ma, Y.; Liu, S.; Shu, H.; Crawford, J.; Xing, Y.; Tao, F. Resveratrol alleviates temporomandibular joint inflammatory pain by recovering disturbed gut microbiota. Brain Behav. Immun., 2020, 87, 455-464.
[http://dx.doi.org/10.1016/j.bbi.2020.01.016] [PMID: 32001342]
[12]
Crock, L.W.; Baldridge, M.T. A role for the microbiota in complex regional pain syndrome? Neurobiol. Pain, 2020, 8, 100054.
[http://dx.doi.org/10.1016/j.ynpai.2020.100054] [PMID: 33305068]
[13]
Cryan, J.F.; O’Riordan, K.J.; Cowan, C.S.M.; Sandhu, K.V.; Bastiaanssen, T.F.S.; Boehme, M.; Codagnone, M.G.; Cussotto, S.; Fulling, C.; Golubeva, A.V.; Guzzetta, K.E.; Jaggar, M.; Long-Smith, C.M.; Lyte, J.M.; Martin, J.A.; Molinero-Perez, A.; Moloney, G.; Morelli, E.; Morillas, E.; O’Connor, R.; Cruz-Pereira, J.S.; Peterson, V.L.; Rea, K.; Ritz, N.L.; Sherwin, E.; Spichak, S.; Teichman, E.M.; van de Wouw, M.; Ventura-Silva, A.P.; Wallace-Fitzsimons, S.E.; Hyland, N.; Clarke, G.; Dinan, T.G. The microbiota-gut-brain axis. Physiol. Rev., 2019, 99(4), 1877-2013.
[http://dx.doi.org/10.1152/physrev.00018.2018] [PMID: 31460832]
[14]
Morita, C.; Tsuji, H.; Hata, T.; Gondo, M.; Takakura, S.; Kawai, K.; Yoshihara, K.; Ogata, K.; Nomoto, K.; Miyazaki, K.; Sudo, N. Gut dysbiosis in patients with anorexia nervosa. PLoS One, 2015, 10(12), e0145274.
[http://dx.doi.org/10.1371/journal.pone.0145274] [PMID: 26682545]
[15]
Unger, M.M.; Spiegel, J.; Dillmann, K.U.; Grundmann, D.; Philippeit, H.; Bürmann, J.; Faßbender, K.; Schwiertz, A.; Schäfer, K.H. Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat. Disord., 2016, 32, 66-72.
[http://dx.doi.org/10.1016/j.parkreldis.2016.08.019] [PMID: 27591074]
[16]
Zhang, L.; Wang, Y.; Xiayu, X.; Shi, C.; Chen, W.; Song, N.; Fu, X.; Zhou, R.; Xu, Y.F.; Huang, L.; Zhu, H.; Han, Y.; Qin, C. Altered gut microbiota in a mouse model of Alzheimer’s disease. J. Alzheimers Dis., 2017, 60(4), 1241-1257.
[http://dx.doi.org/10.3233/JAD-170020] [PMID: 29036812]
[17]
Wang, L.; Christophersen, C.T.; Sorich, M.J.; Gerber, J.P.; Angley, M.T.; Conlon, M.A. Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder. Dig. Dis. Sci., 2012, 57(8), 2096-2102.
[http://dx.doi.org/10.1007/s10620-012-2167-7] [PMID: 22535281]
[18]
Liu, S.; Li, E.; Sun, Z.; Fu, D.; Duan, G.; Jiang, M.; Yu, Y.; Mei, L.; Yang, P.; Tang, Y.; Zheng, P. Altered gut microbiota and short chain fatty acids in Chinese children with autism spectrum disorder. Sci. Rep., 2019, 9(1), 287.
[http://dx.doi.org/10.1038/s41598-018-36430-z] [PMID: 30670726]
[19]
Maltz, R.M.; Keirsey, J.; Kim, S.C.; Mackos, A.R.; Gharaibeh, R.Z.; Moore, C.C.; Xu, J.; Bakthavatchalu, V.; Somogyi, A.; Bailey, M.T. Prolonged restraint stressor exposure in outbred CD-1 mice impacts microbiota, colonic inflammation, and short chain fatty acids. PLoS One, 2018, 13(5), e0196961.
[http://dx.doi.org/10.1371/journal.pone.0196961] [PMID: 29742146]
[20]
Dalile, B.; Van Oudenhove, L.; Vervliet, B.; Verbeke, K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat. Rev. Gastroenterol. Hepatol., 2019, 16(8), 461-478.
[http://dx.doi.org/10.1038/s41575-019-0157-3] [PMID: 31123355]
[21]
Macfarlane, S.; Macfarlane, G.T. Regulation of short-chain fatty acid production. Proc. Nutr. Soc., 2003, 62(1), 67-72.
[http://dx.doi.org/10.1079/PNS2002207] [PMID: 12740060]
[22]
Schönfeld, P.; Wojtczak, L. Short- and medium-chain fatty acids in energy metabolism: The cellular perspective. J. Lipid Res., 2016, 57(6), 943-954.
[http://dx.doi.org/10.1194/jlr.R067629] [PMID: 27080715]
[23]
Bhattacharya, I.; Boje, K.M.K. GHB (gamma-hydroxybutyrate) carrier-mediated transport across the blood-brain barrier. J. Pharmacol. Exp. Ther., 2004, 311(1), 92-98.
[http://dx.doi.org/10.1124/jpet.104.069682] [PMID: 15173314]
[24]
Vijay, N.; Morris, M. Role of monocarboxylate transporters in drug delivery to the brain. Curr. Pharm. Des., 2014, 20(10), 1487-1498.
[http://dx.doi.org/10.2174/13816128113199990462] [PMID: 23789956]
[25]
Oldendorf, W.H. Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids. Am. J. Physiol., 1973, 224(6), 1450-1453.
[http://dx.doi.org/10.1152/ajplegacy.1973.224.6.1450] [PMID: 4712154]
[26]
Silva, Y.P.; Bernardi, A.; Frozza, R.L. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front. Endocrinol. (Lausanne), 2020, 11, 25.
[http://dx.doi.org/10.3389/fendo.2020.00025] [PMID: 32082260]
[27]
Bachmann, C.; Colombo, J.P.; Berüter, J. Short chain fatty acids in plasma and brain: Quantitative determination by gas chromatography. Clin. Chim. Acta, 1979, 92(2), 153-159.
[http://dx.doi.org/10.1016/0009-8981(79)90109-8] [PMID: 487569]
[28]
Braniste, V.; Al-Asmakh, M.; Kowal, C.; Anuar, F.; Abbaspour, A.; Tóth, M.; Korecka, A.; Bakocevic, N.; Ng, L.G.; Kundu, P.; Gulyás, B.; Halldin, C.; Hultenby, K.; Nilsson, H.; Hebert, H.; Volpe, B.T.; Diamond, B.; Pettersson, S. The gut microbiota influences blood-brain barrier permeability in mice. Sci. Transl. Med., 2014, 6(263), 263ra158.
[http://dx.doi.org/10.1126/scitranslmed.3009759] [PMID: 25411471]
[29]
Smith, P.M.; Howitt, M.R.; Panikov, N.; Michaud, M.; Gallini, C.A.; Bohlooly-Y, M.; Glickman, J.N.; Garrett, W.S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 2013, 341(6145), 569-573.
[http://dx.doi.org/10.1126/science.1241165] [PMID: 23828891]
[30]
Zhang, J.; Liu, J.; Zhu, S.; Fang, Y.; Wang, B.; Jia, Q.; Hao, H.; Kao, J.Y.; He, Q.; Song, L.; Liu, F.; Zhu, B.; Owyang, C.; Duan, L. Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation. Acta Pharmacol. Sin., 2021, 42(11), 1821-1833.
[http://dx.doi.org/10.1038/s41401-020-00601-4] [PMID: 33558654]
[31]
Pozuelo, M.; Panda, S.; Santiago, A.; Mendez, S.; Accarino, A.; Santos, J.; Guarner, F.; Azpiroz, F.; Manichanh, C. Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome. Sci. Rep., 2015, 5(1), 12693.
[http://dx.doi.org/10.1038/srep12693] [PMID: 26239401]
[32]
Banasiewicz, T.; Krokowicz, Ł.; Stojcev, Z.; Kaczmarek, B.F.; Kaczmarek, E.; Maik, J.; Marciniak, R.; Krokowicz, P.; Walkowiak, J.; Drews, M. Microencapsulated sodium butyrate reduces the frequency of abdominal pain in patients with irritable bowel syndrome. Colorectal Dis., 2013, 15(2), 204-209.
[http://dx.doi.org/10.1111/j.1463-1318.2012.03152.x] [PMID: 22738315]
[33]
Pituch, A.; Walkowiak, J.; Banaszkiewicz, A. Butyric acid in functional constipation. Prz. Gastroenterol., 2013, 5(5), 295-298.
[http://dx.doi.org/10.5114/pg.2013.38731] [PMID: 24868272]
[34]
Krokowicz, L.; Kaczmarek, B.F.; Krokowicz, P.; Stojcev, Z.; Mackiewicz, J.; Walkowiak, J.; Drews, M.; Banasiewicz, T. Sodium butyrate and short chain fatty acids in prevention of travellers’ diarrhoea: A randomized prospective study. Travel Med. Infect. Dis., 2014, 12(2), 183-188.
[http://dx.doi.org/10.1016/j.tmaid.2013.08.008] [PMID: 24063909]
[35]
He, Y.; Tan, Y.; Zhu, J.; Wu, X.; Huang, Z.; Chen, H.; Yang, M.; Chen, D. Effect of sodium butyrate regulating IRAK1 (interleukin-1 receptor-associated kinase 1) on visceral hypersensitivity in irritable bowel syndrome and its mechanism. Bioengineered, 2021, 12(1), 1436-1444.
[http://dx.doi.org/10.1080/21655979.2021.1920324] [PMID: 33906562]
[36]
Nozu, T.; Miyagishi, S.; Nozu, R.; Takakusaki, K.; Okumura, T. Butyrate inhibits visceral allodynia and colonic hyperpermeability in rat models of irritable bowel syndrome. Sci. Rep., 2019, 9(1), 19603.
[http://dx.doi.org/10.1038/s41598-019-56132-4] [PMID: 31862976]
[37]
Russo, R.; De Caro, C.; Avagliano, C.; Cristiano, C.; La Rana, G.; Mattace Raso, G.; Berni Canani, R.; Meli, R.; Calignano, A. Sodium butyrate and its synthetic amide derivative modulate nociceptive behaviors in mice. Pharmacol. Res., 2016, 103, 279-291.
[http://dx.doi.org/10.1016/j.phrs.2015.11.026] [PMID: 26675718]
[38]
De Caro, C.; Di Cesare Mannelli, L.; Branca, J.J.V.; Micheli, L.; Citraro, R.; Russo, E.; De Sarro, G.; Ghelardini, C.; Calignano, A.; Russo, R. Pain modulation in WAG/Rij epileptic rats (a genetic model of absence epilepsy): Effects of biological and pharmacological histone deacetylase inhibitors. Front. Pharmacol., 2020, 11, 549191.
[http://dx.doi.org/10.3389/fphar.2020.549191] [PMID: 33343343]
[39]
Lanza, M.; Filippone, A.; Ardizzone, A.; Casili, G.; Paterniti, I.; Esposito, E.; Campolo, M. SCFA treatment alleviates pathological signs of migraine and related intestinal alterations in a mouse model of NTG-induced migraine. Cells, 2021, 10(10), 2756.
[http://dx.doi.org/10.3390/cells10102756] [PMID: 34685736]
[40]
Lanza, M.; Filippone, A.; Casili, G.; Giuffrè, L.; Scuderi, S.A.; Paterniti, I.; Campolo, M.; Cuzzocrea, S.; Esposito, E. Supplementation with SCFAs Re-Establishes microbiota composition and attenuates hyperalgesia and pain in a mouse model of NTG-induced migraine. Int. J. Mol. Sci., 2022, 23(9), 4847.
[http://dx.doi.org/10.3390/ijms23094847] [PMID: 35563235]
[41]
Rosser, E.C.; Piper, C.J.M.; Matei, D.E.; Blair, P.A.; Rendeiro, A.F.; Orford, M.; Alber, D.G.; Krausgruber, T.; Catalan, D.; Klein, N.; Manson, J.J.; Drozdov, I.; Bock, C.; Wedderburn, L.R.; Eaton, S.; Mauri, C. Microbiota-derived metabolites suppress arthritis by amplifying aryl-hydrocarbon receptor activation in regulatory B cells. Cell Metab., 2020, 31(4), 837-851.e10.
[http://dx.doi.org/10.1016/j.cmet.2020.03.003] [PMID: 32213346]
[42]
Filippone, A.; Lanza, M.; Campolo, M.; Casili, G.; Paterniti, I.; Cuzzocrea, S.; Esposito, E. The anti-inflammatory and antioxidant effects of sodium propionate. Int. J. Mol. Sci., 2020, 21(8), 3026.
[http://dx.doi.org/10.3390/ijms21083026] [PMID: 32344758]
[43]
Balmer, M.L.; Ma, E.H.; Thompson, A.J.; Epple, R.; Unterstab, G.; Lötscher, J.; Dehio, P.; Schürch, C.M.; Warncke, J.D.; Perrin, G.; Woischnig, A.K.; Grählert, J.; Löliger, J.; Assmann, N.; Bantug, G.R.; Schären, O.P.; Khanna, N.; Egli, A.; Bubendorf, L.; Rentsch, K.; Hapfelmeier, S.; Jones, R.G.; Hess, C. Memory CD8+ T cells balance Pro- and anti-inflammatory activity by reprogramming cellular acetate handling at sites of infection. Cell Metab., 2020, 32(3), 457-467.e5.
[http://dx.doi.org/10.1016/j.cmet.2020.07.004] [PMID: 32738204]
[44]
Reisenauer, C.J.; Bhatt, D.P.; Mitteness, D.J.; Slanczka, E.R.; Gienger, H.M.; Watt, J.A.; Rosenberger, T.A. Acetate supplementation attenuates lipopolysaccharide-induced neuroinflammation. J. Neurochem., 2011, 117(2), 264-274.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07198.x] [PMID: 21272004]
[45]
Soliman, M.L.; Smith, M.D.; Houdek, H.M.; Rosenberger, T.A. Acetate supplementation modulates brain histone acetylation and decreases interleukin-1β expression in a rat model of neuroinflammation. J. Neuroinflammation, 2012, 9(1), 51.
[http://dx.doi.org/10.1186/1742-2094-9-51] [PMID: 22413888]
[46]
Xu, M.; Wang, C.; Li, N.; Wang, J.; Zhang, Y.; Deng, X. Intraperitoneal injection of acetate protects mice against lipopolysaccharide (LPS) induced acute lung injury through its anti-inflammatory and anti-oxidative ability. Med. Sci. Monit., 2019, 25, 2278-2288.
[http://dx.doi.org/10.12659/MSM.911444] [PMID: 30921298]
[47]
Huda-Faujan, N.; Abdulamir, A.S.; Fatimah, A.B.; Anas, O.M.; Shuhaimi, M.; Yazid, A.M.; Loong, Y.Y. The impact of the level of the intestinal short chain Fatty acids in inflammatory bowel disease patients versus healthy subjects. Open Biochem. J., 2010, 4, 53-58.
[http://dx.doi.org/10.2174/1874091X01004010053] [PMID: 20563285]
[48]
Long, X.; Li, M.; Li, L.X.; Sun, Y.Y.; Zhang, W.X.; Zhao, D.Y.; Li, Y.Q. Butyrate promotes visceral hypersensitivity in an IBS-like model via enteric glial cell-derived nerve growth factor. Neurogastroenterol. Motil., 2018, 30(4), e13227.
[http://dx.doi.org/10.1111/nmo.13227] [PMID: 29052293]
[49]
Esquerre, N.; Basso, L.; Defaye, M.; Vicentini, F.A.; Cluny, N.; Bihan, D.; Hirota, S.A.; Schick, A.; Jijon, H.B.; Lewis, I.A.; Geuking, M.B.; Sharkey, K.A.; Altier, C.; Nasser, Y. Colitis-induced microbial perturbation promotes postinflammatory visceral hypersensitivity. Cell. Mol. Gastroenterol. Hepatol., 2020, 10(2), 225-244.
[http://dx.doi.org/10.1016/j.jcmgh.2020.04.003] [PMID: 32289500]
[50]
Tan, J.; McKenzie, C.; Potamitis, M.; Thorburn, A.N.; Mackay, C.R.; Macia, L. The role of short-chain fatty acids in health and disease. Adv. Immunol., 2014, 121, 91-119.
[http://dx.doi.org/10.1016/B978-0-12-800100-4.00003-9] [PMID: 24388214]
[51]
Sivaprakasam, S.; Bhutia, Y.D.; Yang, S.; Ganapathy, V. Short-chain fatty acid transporters: Role in colonic homeostasis. Compr. Physiol., 2017, 8(1), 299-314.
[http://dx.doi.org/10.1002/cphy.c170014] [PMID: 29357130]
[52]
You, H.; Tan, Y.; Yu, D.; Qiu, S.; Bai, Y.; He, J.; Cao, H.; Che, Q.; Guo, J.; Su, Z. The Therapeutic effect of SCFA-mediated regulation of the intestinal environment on obesity. Front. Nutr., 2022, 9, 886902.
[http://dx.doi.org/10.3389/fnut.2022.886902] [PMID: 35662937]
[53]
Brown, A.J.; Goldsworthy, S.M.; Barnes, A.A.; Eilert, M.M.; Tcheang, L.; Daniels, D.; Muir, A.I.; Wigglesworth, M.J.; Kinghorn, I.; Fraser, N.J.; Pike, N.B.; Strum, J.C.; Steplewski, K.M.; Murdock, P.R.; Holder, J.C.; Marshall, F.H.; Szekeres, P.G.; Wilson, S.; Ignar, D.M.; Foord, S.M.; Wise, A.; Dowell, S.J. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem., 2003, 278(13), 11312-11319.
[http://dx.doi.org/10.1074/jbc.M211609200] [PMID: 12496283]
[54]
Le Poul, E.; Loison, C.; Struyf, S.; Springael, J.Y.; Lannoy, V.; Decobecq, M.E.; Brezillon, S.; Dupriez, V.; Vassart, G.; Van Damme, J.; Parmentier, M.; Detheux, M. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem., 2003, 278(28), 25481-25489.
[http://dx.doi.org/10.1074/jbc.M301403200] [PMID: 12711604]
[55]
Nilsson, N.E.; Kotarsky, K.; Owman, C.; Olde, B. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem. Biophys. Res. Commun., 2003, 303(4), 1047-1052.
[http://dx.doi.org/10.1016/S0006-291X(03)00488-1] [PMID: 12684041]
[56]
Tolhurst, G.; Heffron, H.; Lam, Y.S.; Parker, H.E.; Habib, A.M.; Diakogiannaki, E.; Cameron, J.; Grosse, J.; Reimann, F.; Gribble, F.M. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes, 2012, 61(2), 364-371.
[http://dx.doi.org/10.2337/db11-1019] [PMID: 22190648]
[57]
Nøhr, M.K.; Egerod, K.L.; Christiansen, S.H.; Gille, A.; Offermanns, S.; Schwartz, T.W.; Møller, M. Expression of the short chain fatty acid receptor GPR41/FFAR3 in autonomic and somatic sensory ganglia. Neuroscience, 2015, 290, 126-137.
[http://dx.doi.org/10.1016/j.neuroscience.2015.01.040] [PMID: 25637492]
[58]
Kimura, I.; Inoue, D.; Maeda, T.; Hara, T.; Ichimura, A.; Miyauchi, S.; Kobayashi, M.; Hirasawa, A.; Tsujimoto, G. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc. Natl. Acad. Sci. USA, 2011, 108(19), 8030-8035.
[http://dx.doi.org/10.1073/pnas.1016088108] [PMID: 21518883]
[59]
Bonini, J.A.; Anderson, S.M.; Steiner, D.F. Molecular cloning and tissue expression of a novel orphan G protein-coupled receptor from rat lung. Biochem. Biophys. Res. Commun., 1997, 234(1), 190-193.
[http://dx.doi.org/10.1006/bbrc.1997.6591] [PMID: 9168987]
[60]
Iwanaga, T.; Takebe, K.; Kato, I.; Karaki, S.I.; Kuwahara, A. Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8. Biomed. Res., 2006, 27(5), 243-254.
[http://dx.doi.org/10.2220/biomedres.27.243] [PMID: 17099289]
[61]
Waldecker, M.; Kautenburger, T.; Daumann, H.; Busch, C.; Schrenk, D. Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon. J. Nutr. Biochem., 2008, 19(9), 587-593.
[http://dx.doi.org/10.1016/j.jnutbio.2007.08.002] [PMID: 18061431]
[62]
Soliman, M.L.; Rosenberger, T.A. Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression. Mol. Cell. Biochem., 2011, 352(1-2), 173-180.
[http://dx.doi.org/10.1007/s11010-011-0751-3] [PMID: 21359531]
[63]
Wang, W.; Cui, S.; Lu, R.; Zhang, H. Is there any therapeutic value for the use of histone deacetylase inhibitors for chronic pain? Brain Res. Bull., 2016, 125, 44-52.
[http://dx.doi.org/10.1016/j.brainresbull.2016.04.010] [PMID: 27090944]
[64]
Penas, C.; Navarro, X. Epigenetic modifications associated to neuroinflammation and neuropathic pain after neural trauma. Front. Cell. Neurosci., 2018, 12, 158.
[http://dx.doi.org/10.3389/fncel.2018.00158] [PMID: 29930500]
[65]
Schroeder, F.A.; Lin, C.L.; Crusio, W.E.; Akbarian, S. Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol. Psychiatry, 2007, 62(1), 55-64.
[http://dx.doi.org/10.1016/j.biopsych.2006.06.036] [PMID: 16945350]
[66]
Fischer, A.; Sananbenesi, F.; Wang, X.; Dobbin, M.; Tsai, L.H. Recovery of learning and memory is associated with chromatin remodelling. Nature, 2007, 447(7141), 178-182.
[http://dx.doi.org/10.1038/nature05772] [PMID: 17468743]
[67]
Stafford, J.M.; Raybuck, J.D.; Ryabinin, A.E.; Lattal, K.M. Increasing histone acetylation in the hippocampus-infralimbic network enhances fear extinction. Biol. Psychiatry, 2012, 72(1), 25-33.
[http://dx.doi.org/10.1016/j.biopsych.2011.12.012] [PMID: 22290116]
[68]
Cousens, L.S.; Gallwitz, D.; Alberts, B.M. Different accessibilities in chromatin to histone acetylase. J. Biol. Chem., 1979, 254(5), 1716-1723.
[http://dx.doi.org/10.1016/S0021-9258(17)37831-6] [PMID: 762168]
[69]
Descalzi, G.; Ikegami, D.; Ushijima, T.; Nestler, E.J.; Zachariou, V.; Narita, M. Epigenetic mechanisms of chronic pain. Trends Neurosci., 2015, 38(4), 237-246.
[http://dx.doi.org/10.1016/j.tins.2015.02.001] [PMID: 25765319]
[70]
Cherng, C.H.; Lee, K.C.; Chien, C.C.; Chou, K.Y.; Cheng, Y.C.; Hsin, S.T.; Lee, S.O.; Shen, C.H.; Tsai, R.Y.; Wong, C.S. Baicalin ameliorates neuropathic pain by suppressing HDAC1 expression in the spinal cord of spinal nerve ligation rats. J. Formos. Med. Assoc., 2014, 113(8), 513-520.
[http://dx.doi.org/10.1016/j.jfma.2013.04.007] [PMID: 23684218]
[71]
Yuan, L.; Liu, C.; Wan, Y.; Yan, H.; Li, T. Effect of HDAC2/Inpp5f on neuropathic pain and cognitive function through regulating PI3K/Akt/GSK-3β signal pathway in rats with neuropathic pain. Exp. Ther. Med., 2019, 18(1), 678-684.
[http://dx.doi.org/10.3892/etm.2019.7622] [PMID: 31281447]
[72]
Kukkar, A.; Singh, N.; Jaggi, A.S. Attenuation of neuropathic pain by sodium butyrate in an experimental model of chronic constriction injury in rats. J. Formos. Med. Assoc., 2014, 113(12), 921-928.
[http://dx.doi.org/10.1016/j.jfma.2013.05.013] [PMID: 23870713]
[73]
Mao, Y.; Zhou, J.; Liu, X.; Gu, E.; Zhang, Z.; Tao, W. Comparison of different histone deacetylase inhibitors in attenuating inflammatory pain in rats. Pain Res. Manag., 2019, 2019, 1-10.
[http://dx.doi.org/10.1155/2019/1648919] [PMID: 30809320]
[74]
Romanelli, M.N.; Borgonetti, V.; Galeotti, N. Dual BET/HDAC inhibition to relieve neuropathic pain: Recent advances, perspectives, and future opportunities. Pharmacol. Res., 2021, 173, 105901.
[http://dx.doi.org/10.1016/j.phrs.2021.105901] [PMID: 34547384]
[75]
Borgonetti, V.; Meacci, E.; Pierucci, F.; Romanelli, M.N.; Galeotti, N. Dual HDAC/BRD4 inhibitors relieves neuropathic pain by attenuating inflammatory response in microglia after spared nerve injury. Neurotherapeutics, 2022, 173, 105901.
[http://dx.doi.org/10.1007/s13311-022-01243-6] [PMID: 35501470]
[76]
Zhang, Z.; Cai, Y.Q.; Zou, F.; Bie, B.; Pan, Z.Z. Epigenetic suppression of GAD65 expression mediates persistent pain. Nat. Med., 2011, 17(11), 1448-1455.
[http://dx.doi.org/10.1038/nm.2442] [PMID: 21983856]
[77]
Hou, X.; Weng, Y.; Ouyang, B.; Ding, Z.; Song, Z.; Zou, W.; Huang, C.; Guo, Q. HDAC inhibitor TSA ameliorates mechanical hypersensitivity and potentiates analgesic effect of morphine in a rat model of bone cancer pain by restoring μ-opioid receptor in spinal cord. Brain Res., 2017, 1669, 97-105.
[http://dx.doi.org/10.1016/j.brainres.2017.05.014] [PMID: 28559159]
[78]
Zammataro, M.; Sortino, M.A.; Parenti, C.; Gereau, R.W., IV; Chiechio, S. HDAC and HAT inhibitors differently affect analgesia mediated by group II metabotropic glutamate receptors. Mol. Pain, 2014, 10, 1744-8069-10-68.
[http://dx.doi.org/10.1186/1744-8069-10-68] [PMID: 25406541]
[79]
Matsushita, Y.; Araki, K.; Omotuyi, O.; Mukae, T.; Ueda, H. HDAC inhibitors restore C-fibre sensitivity in experimental neuropathic pain model. Br. J. Pharmacol., 2013, 170(5), 991-998.
[http://dx.doi.org/10.1111/bph.12366] [PMID: 24032674]
[80]
He, X.T.; Hu, X.F.; Zhu, C.; Zhou, K.X.; Zhao, W.J.; Zhang, C.; Han, X.; Wu, C.L.; Wei, Y.Y.; Wang, W.; Deng, J.P.; Chen, F.M.; Gu, Z.X.; Dong, Y.L. Suppression of histone deacetylases by SAHA relieves bone cancer pain in rats via inhibiting activation of glial cells in spinal dorsal horn and dorsal root ganglia. J. Neuroinflammation, 2020, 17(1), 125.
[http://dx.doi.org/10.1186/s12974-020-01740-5] [PMID: 32321538]
[81]
Borgonetti, V.; Galeotti, N. Combined inhibition of histone deacetylases and BET family proteins as epigenetic therapy for nerve injury-induced neuropathic pain. Pharmacol. Res., 2021, 165, 105431.
[http://dx.doi.org/10.1016/j.phrs.2021.105431] [PMID: 33529752]
[82]
Winkler, I.; Blotnik, S.; Shimshoni, J.; Yagen, B.; Devor, M.; Bialer, M. Efficacy of antiepileptic isomers of valproic acid and valpromide in a rat model of neuropathic pain. Br. J. Pharmacol., 2005, 146(2), 198-208.
[http://dx.doi.org/10.1038/sj.bjp.0706310] [PMID: 15997234]
[83]
Sabari, B.R.; Tang, Z.; Huang, H.; Yong-Gonzalez, V.; Molina, H.; Kong, H.E.; Dai, L.; Shimada, M.; Cross, J.R.; Zhao, Y.; Roeder, R.G.; Allis, C.D. Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation. Mol. Cell, 2015, 58(2), 203-215.
[http://dx.doi.org/10.1016/j.molcel.2015.02.029] [PMID: 25818647]
[84]
Fellows, R.; Denizot, J.; Stellato, C.; Cuomo, A.; Jain, P.; Stoyanova, E.; Balázsi, S.; Hajnády, Z.; Liebert, A.; Kazakevych, J.; Blackburn, H.; Corrêa, R.O.; Fachi, J.L.; Sato, F.T.; Ribeiro, W.R.; Ferreira, C.M.; Perée, H.; Spagnuolo, M.; Mattiuz, R.; Matolcsi, C.; Guedes, J.; Clark, J.; Veldhoen, M.; Bonaldi, T.; Vinolo, M.A.R.; Varga-Weisz, P. Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. Nat. Commun., 2018, 9(1), 105.
[http://dx.doi.org/10.1038/s41467-017-02651-5] [PMID: 29317660]
[85]
Chriett, S.; Dąbek, A.; Wojtala, M.; Vidal, H.; Balcerczyk, A.; Pirola, L. Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. Sci. Rep., 2019, 9(1), 742.
[http://dx.doi.org/10.1038/s41598-018-36941-9] [PMID: 30679586]
[86]
Oleskin, A.V.; Shenderov, B.A. Neuromodulatory effects and targets of the SCFAs and gasotransmitters produced by the human symbiotic microbiota. Microb. Ecol. Health Dis., 2016, 27, 30971.
[PMID: 27389418]
[87]
Frost, G.; Sleeth, M.L.; Sahuri-Arisoylu, M.; Lizarbe, B.; Cerdan, S.; Brody, L.; Anastasovska, J.; Ghourab, S.; Hankir, M.; Zhang, S.; Carling, D.; Swann, J.R.; Gibson, G.; Viardot, A.; Morrison, D.; Louise Thomas, E.; Bell, J.D. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat. Commun., 2014, 5(1), 3611.
[http://dx.doi.org/10.1038/ncomms4611] [PMID: 24781306]
[88]
Peek, A.L.; Rebbeck, T.; Puts, N.A.J.; Watson, J.; Aguila, M.E.R.; Leaver, A.M. Brain GABA and glutamate levels across pain conditions: A systematic literature review and meta-analysis of 1H-MRS studies using the MRS-Q quality assessment tool. Neuroimage, 2020, 210, 116532.
[http://dx.doi.org/10.1016/j.neuroimage.2020.116532] [PMID: 31958584]
[89]
Clarke, G.; Stilling, R.M.; Kennedy, P.J.; Stanton, C.; Cryan, J.F.; Dinan, T.G. Minireview: Gut microbiota: The neglected endocrine organ. Mol. Endocrinol., 2014, 28(8), 1221-1238.
[http://dx.doi.org/10.1210/me.2014-1108] [PMID: 24892638]
[90]
Hooten, W.M. Chronic pain and mental health disorders. Mayo Clin. Proc., 2016, 91(7), 955-970.
[http://dx.doi.org/10.1016/j.mayocp.2016.04.029] [PMID: 27344405]
[91]
Savignac, H.M.; Corona, G.; Mills, H.; Chen, L.; Spencer, J.P.E.; Tzortzis, G.; Burnet, P.W.J. Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-d-aspartate receptor subunits and d-serine. Neurochem. Int., 2013, 63(8), 756-764.
[http://dx.doi.org/10.1016/j.neuint.2013.10.006] [PMID: 24140431]
[92]
Barichello, T.; Generoso, J.S.; Simões, L.R.; Faller, C.J.; Ceretta, R.A.; Petronilho, F.; Lopes-Borges, J.; Valvassori, S.S.; Quevedo, J. Sodium butyrate prevents memory impairment by re-establishing BDNF and GDNF expression in experimental pneumococcal meningitis. Mol. Neurobiol., 2015, 52(1), 734-740.
[http://dx.doi.org/10.1007/s12035-014-8914-3] [PMID: 25284351]
[93]
Varela, R.B.; Valvassori, S.S.; Lopes-Borges, J.; Mariot, E.; Dal-Pont, G.C.; Amboni, R.T.; Bianchini, G.; Quevedo, J. Sodium butyrate and mood stabilizers block ouabain-induced hyperlocomotion and increase BDNF, NGF and GDNF levels in brain of Wistar rats. J. Psychiatr. Res., 2015, 61, 114-121.
[http://dx.doi.org/10.1016/j.jpsychires.2014.11.003] [PMID: 25467060]
[94]
Obara, I.; Telezhkin, V.; Alrashdi, I.; Chazot, P.L. Histamine, histamine receptors, and neuropathic pain relief. Br. J. Pharmacol., 2020, 177(3), 580-599.
[http://dx.doi.org/10.1111/bph.14696] [PMID: 31046146]
[95]
Cui, J.G.; Linderoth, B.; Meyerson, B.A. Effects of spinal cord stimulation on touch-evoked allodynia involve GABAergic mechanisms. An experimental study in the mononeuropathic rat. Pain, 1996, 66(2), 287-295.
[http://dx.doi.org/10.1016/0304-3959(96)03069-2] [PMID: 8880852]
[96]
Wang, C.; Gu, L.; Ruan, Y.; Geng, X.; Xu, M.; Yang, N.; Yu, L.; Jiang, Y.; Zhu, C.; Yang, Y.; Zhou, Y.; Guan, X.; Luo, W.; Liu, Q.; Dong, X.; Yu, G.; Lan, L.; Tang, Z. Facilitation of MrgprD by TRP‐A1 promotes neuropathic pain. FASEB J., 2019, 33(1), 1360-1373.
[http://dx.doi.org/10.1096/fj.201800615RR] [PMID: 30148678]
[97]
Kinfe, T.; Buchfelder, M.; Chaudhry, S.; Chakravarthy, K.; Deer, T.; Russo, M.; Georgius, P.; Hurlemann, R.; Rasheed, M.; Muhammad, S.; Yearwood, T. Leptin and associated mediators of immunometabolic signaling: Novel molecular outcome measures for neurostimulation to treat chronic pain. Int. J. Mol. Sci., 2019, 20(19), 4737.
[http://dx.doi.org/10.3390/ijms20194737] [PMID: 31554241]
[98]
Hassan, A.M.; Jain, P.; Mayerhofer, R.; Fröhlich, E.E.; Farzi, A.; Reichmann, F.; Herzog, H.; Holzer, P. Visceral hyperalgesia caused by peptide YY deletion and Y2 receptor antagonism. Sci. Rep., 2017, 7(1), 40968.
[http://dx.doi.org/10.1038/srep40968] [PMID: 28106168]
[99]
Apkarian, A.V.; Bushnell, M.C.; Treede, R.D.; Zubieta, J.K. Human brain mechanisms of pain perception and regulation in health and disease. Eur. J. Pain, 2005, 9(4), 463-484.
[http://dx.doi.org/10.1016/j.ejpain.2004.11.001] [PMID: 15979027]
[100]
Psichas, A.; Sleeth, M.L.; Murphy, K.G.; Brooks, L.; Bewick, G.A.; Hanyaloglu, A.C.; Ghatei, M.A.; Bloom, S.R.; Frost, G. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int. J. Obes., 2015, 39(3), 424-429.
[http://dx.doi.org/10.1038/ijo.2014.153] [PMID: 25109781]
[101]
Larraufie, P.; Martin-Gallausiaux, C.; Lapaque, N.; Dore, J.; Gribble, F.M.; Reimann, F.; Blottiere, H.M. SCFAs strongly stimulate PYY production in human enteroendocrine cells. Sci. Rep., 2018, 8(1), 74.
[http://dx.doi.org/10.1038/s41598-017-18259-0] [PMID: 29311617]
[102]
Cani, P.D.; Lecourt, E.; Dewulf, E.M.; Sohet, F.M.; Pachikian, B.D.; Naslain, D.; De Backer, F.; Neyrinck, A.M.; Delzenne, N.M. Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am. J. Clin. Nutr., 2009, 90(5), 1236-1243.
[http://dx.doi.org/10.3945/ajcn.2009.28095] [PMID: 19776140]
[103]
Trapp, S.; Richards, J.E. The gut hormone glucagon-like peptide-1 produced in brain: Is this physiologically relevant? Curr. Opin. Pharmacol., 2013, 13(6), 964-969.
[http://dx.doi.org/10.1016/j.coph.2013.09.006] [PMID: 24075717]
[104]
Yang, Y.; Cui, X.; Chen, Y.; Wang, Y.; Li, X.; Lin, L.; Zhang, H. Exendin-4, an analogue of glucagon-like peptide-1, attenuates hyperalgesia through serotonergic pathways in rats with neonatal colonic sensitivity. J. Physiol. Pharmacol., 2014, 65(3), 349-357.
[PMID: 24930506]
[105]
Li, Z.Y.; Zhang, N.; Wen, S.; Zhang, J.; Sun, X.L.; Fan, X.M.; Sun, Y.H. Decreased glucagon-like peptide-1 correlates with abdominal pain in patients with constipation-predominant irritable bowel syndrome. Clin. Res. Hepatol. Gastroenterol., 2017, 41(4), 459-465.
[http://dx.doi.org/10.1016/j.clinre.2016.12.007] [PMID: 28215540]
[106]
O’Malley, D. Endocrine regulation of gut function - a role for glucagon-like peptide-1 in the pathophysiology of irritable bowel syndrome. Exp. Physiol., 2019, 104(1), 3-10.
[PMID: 30444291]
[107]
Hellström, P.M.; Hein, J.; Bytzer, P.; Björnssön, E.; Kristensen, J.; Schambye, H. Clinical trial: the glucagon-like peptide-1 analogue ROSE-010 for management of acute pain in patients with irritable bowel syndrome: A randomized, placebo-controlled, double-blind study. Aliment. Pharmacol. Ther., 2009, 29(2), 198-206.
[http://dx.doi.org/10.1111/j.1365-2036.2008.03870.x] [PMID: 18945254]
[108]
Tang, X.; Wu, H.; Mao, X.; Li, X.; Wang, Y. The GLP-1 receptor herbal agonist morroniside attenuates neuropathic pain via spinal microglial expression of IL-10 and β-endorphin. Biochem. Biophys. Res. Commun., 2020, 530(3), 494-499.
[http://dx.doi.org/10.1016/j.bbrc.2020.05.080] [PMID: 32595037]
[109]
Wang, Y.R.; Mao, X.F.; Wu, H.Y.; Wang, Y.X. Liposome-encapsulated clodronate specifically depletes spinal microglia and reduces initial neuropathic pain. Biochem. Biophys. Res. Commun., 2018, 499(3), 499-505.
[http://dx.doi.org/10.1016/j.bbrc.2018.03.177] [PMID: 29596830]
[110]
Morimoto, R.; Satoh, F.; Murakami, O.; Totsune, K.; Saruta, M.; Suzuki, T.; Sasano, H.; Ito, S.; Takahashi, K. Expression of peptide YY in human brain and pituitary tissues. Nutrition, 2008, 24(9), 878-884.
[http://dx.doi.org/10.1016/j.nut.2008.06.011] [PMID: 18662857]
[111]
Nonaka, N.; Shioda, S.; Niehoff, M.L.; Banks, W.A. Characterization of blood-brain barrier permeability to PYY3-36 in the mouse. J. Pharmacol. Exp. Ther., 2003, 306(3), 948-953.
[http://dx.doi.org/10.1124/jpet.103.051821] [PMID: 12750431]
[112]
Koda, S.; Date, Y.; Murakami, N.; Shimbara, T.; Hanada, T.; Toshinai, K.; Niijima, A.; Furuya, M.; Inomata, N.; Osuye, K.; Nakazato, M. The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats. Endocrinology, 2005, 146(5), 2369-2375.
[http://dx.doi.org/10.1210/en.2004-1266] [PMID: 15718279]
[113]
Waise, T.M.Z.; Dranse, H.J.; Lam, T.K.T. The metabolic role of vagal afferent innervation. Nat. Rev. Gastroenterol. Hepatol., 2018, 15(10), 625-636.
[http://dx.doi.org/10.1038/s41575-018-0062-1] [PMID: 30185916]
[114]
Ly, H.G.; Dupont, P.; Van Laere, K.; Depoortere, I.; Tack, J.; Van Oudenhove, L. Differential brain responses to gradual intragastric nutrient infusion and gastric balloon distension: A role for gut peptides? Neuroimage., 2017, 144(Pt A), 101-112.
[http://dx.doi.org/10.1016/j.neuroimage.2016.09.032] [PMID: 27639359]
[115]
Gibbs, J.L.; Diogenes, A.; Hargreaves, K.M. Neuropeptide Y modulates effects of bradykinin and prostaglandin E2 on trigeminal nociceptors via activation of the Y1 and Y2 receptors. Br. J. Pharmacol., 2007, 150(1), 72-79.
[http://dx.doi.org/10.1038/sj.bjp.0706967] [PMID: 17143304]
[116]
Paredes, S.; Cantillo, S.; Candido, K.D.; Knezevic, N.N. An Association of Serotonin with Pain Disorders and Its Modulation by Estrogens. Int. J. Mol. Sci., 2019, 20(22), 5729.
[http://dx.doi.org/10.3390/ijms20225729] [PMID: 31731606]
[117]
Gershon, M.D.; Tack, J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology, 2007, 132(1), 397-414.
[http://dx.doi.org/10.1053/j.gastro.2006.11.002] [PMID: 17241888]
[118]
Bonaz, B.; Bazin, T.; Pellissier, S. The vagus nerve at the interface of the microbiota-gut-brain Axis. Front. Neurosci., 2018, 12, 49.
[http://dx.doi.org/10.3389/fnins.2018.00049] [PMID: 29467611]
[119]
Reigstad, C.S.; Salmonson, C.E.; Iii, J.F.R.; Szurszewski, J.H.; Linden, D.R.; Sonnenburg, J.L.; Farrugia, G.; Kashyap, P.C. Gut microbes promote colonic serotonin production through an effect of short‐chain fatty acids on enterochromaffin cells. FASEB J., 2015, 29(4), 1395-1403.
[http://dx.doi.org/10.1096/fj.14-259598] [PMID: 25550456]
[120]
Fukumoto, S.; Tatewaki, M.; Yamada, T.; Fujimiya, M.; Mantyh, C.; Voss, M.; Eubanks, S.; Harris, M.; Pappas, T.N.; Takahashi, T. Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2003, 284(5), R1269-R1276.
[http://dx.doi.org/10.1152/ajpregu.00442.2002] [PMID: 12676748]
[121]
Yano, J.M.; Yu, K.; Donaldson, G.P.; Shastri, G.G.; Ann, P.; Ma, L.; Nagler, C.R.; Ismagilov, R.F.; Mazmanian, S.K.; Hsiao, E.Y. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 2015, 161(2), 264-276.
[http://dx.doi.org/10.1016/j.cell.2015.02.047] [PMID: 25860609]
[122]
Srikanthan, K.; Feyh, A.; Visweshwar, H.; Shapiro, J.I.; Sodhi, K. Systematic review of metabolic syndrome biomarkers: A panel for early detection, management, and risk stratification in the west virginian population. Int. J. Med. Sci., 2016, 13(1), 25-38.
[http://dx.doi.org/10.7150/ijms.13800] [PMID: 26816492]
[123]
Byrne, C.S.; Chambers, E.S.; Morrison, D.J.; Frost, G. The role of short chain fatty acids in appetite regulation and energy homeostasis. Int. J. Obes., 2015, 39(9), 1331-1338.
[http://dx.doi.org/10.1038/ijo.2015.84] [PMID: 25971927]
[124]
Ezquerro, S.; Frühbeck, G.; Rodríguez, A. Ghrelin and autophagy. Curr. Opin. Clin. Nutr. Metab. Care, 2017, 20(5), 402-408.
[http://dx.doi.org/10.1097/MCO.0000000000000390] [PMID: 28590260]
[125]
Raghay, K.; Akki, R.; Bensaid, D.; Errami, M. Ghrelin as an anti-inflammatory and protective agent in ischemia/reperfusion injury. Peptides, 2020, 124, 170226.
[http://dx.doi.org/10.1016/j.peptides.2019.170226] [PMID: 31786283]
[126]
Yamashita, K.; Yamamoto, K.; Takata, A.; Miyazaki, Y.; Saito, T.; Tanaka, K.; Makino, T.; Takahashi, T.; Kurokawa, Y.; Yamasaki, M.; Mano, M.; Nakajima, K.; Eguchi, H.; Doki, Y. Continuous ghrelin infusion attenuates the postoperative inflammatory response in patients with esophageal cancer. Esophagus, 2021, 18(2), 239-247.
[http://dx.doi.org/10.1007/s10388-020-00776-z] [PMID: 32856182]
[127]
Pirzadeh, S.; Sajedianfard, J.; Aloisi, A.M.; Ashrafi, M. Effects of intracerebroventricular and intra-arcuate nucleus injection of ghrelin on pain behavioral responses and met-enkephalin and β-endorphin concentrations in the periaqueductal gray area in rats. Int. J. Mol. Sci., 2019, 20(10), 2475.
[http://dx.doi.org/10.3390/ijms20102475] [PMID: 31109149]
[128]
Carniglia, L.; Ramírez, D.; Durand, D.; Saba, J.; Turati, J.; Caruso, C.; Scimonelli, T.N.; Lasaga, M. Neuropeptides and microglial activation in inflammation, pain, and neurodegenerative diseases. Mediators Inflamm., 2017, 2017, 1-23.
[http://dx.doi.org/10.1155/2017/5048616] [PMID: 28154473]
[129]
Zhou, C.H.; Li, X.; Zhu, Y.Z.; Huang, H.; Li, J.; Liu, L.; Hu, Q.; Ma, T.F.; Shao, Y.; Wu, Y.Q. Ghrelin alleviates neuropathic pain through GHSR-1a-mediated suppression of the p38 MAPK/NF-κB pathway in a rat chronic constriction injury model. Reg. Anesth. Pain Med., 2014, 39(2), 137-148.
[http://dx.doi.org/10.1097/AAP.0000000000000050] [PMID: 24513955]
[130]
Fukumori, R.; Sugino, T.; Hasegawa, Y.; Kojima, M.; Kangawa, K.; Obitsu, T.; Taniguchi, K. Plasma ghrelin concentration is decreased by short chain fatty acids in wethers. Domest. Anim. Endocrinol., 2011, 41(1), 50-55.
[http://dx.doi.org/10.1016/j.domaniend.2011.04.001] [PMID: 21645807]
[131]
Okine, B.N.; Gaspar, J.C.; Finn, D.P. PPARs and pain. Br. J. Pharmacol., 2019, 176(10), 1421-1442.
[http://dx.doi.org/10.1111/bph.14339] [PMID: 29679493]
[132]
Manickam, R.; Duszka, K.; Wahli, W. PPARs and microbiota in skeletal muscle health and wasting. Int. J. Mol. Sci., 2020, 21(21), 8056.
[http://dx.doi.org/10.3390/ijms21218056] [PMID: 33137899]
[133]
Higashimura, Y.; Naito, Y.; Takagi, T.; Uchiyama, K.; Mizushima, K.; Yoshikawa, T. Propionate promotes fatty acid oxidation through the up-regulation of peroxisome proliferator-activated Receptor α in intestinal epithelial cells. J. Nutr. Sci. Vitaminol. (Tokyo), 2015, 61(6), 511-515.
[http://dx.doi.org/10.3177/jnsv.61.511] [PMID: 26875495]
[134]
Leong, W.; Huang, G.; Liao, W.; Xia, W.; Li, X.; Su, Z.; Liu, L.; Wu, Q.; Wong, V.K.W.; Law, B.Y.K.; Xia, C.; Guo, X.; Khan, I.; Wendy Hsiao, W.L. Traditional Patchouli essential oil modulates the host’s immune responses and gut microbiota and exhibits potent anti-cancer effects in Apc mice. Pharmacol. Res., 2022, 176, 106082.
[http://dx.doi.org/10.1016/j.phrs.2022.106082] [PMID: 35032662]
[135]
Alex, S.; Lange, K.; Amolo, T.; Grinstead, J.S.; Haakonsson, A.K.; Szalowska, E.; Koppen, A.; Mudde, K.; Haenen, D.; Al-Lahham, S.; Roelofsen, H.; Houtman, R.; van der Burg, B.; Mandrup, S.; Bonvin, A.M.J.J.; Kalkhoven, E.; Müller, M.; Hooiveld, G.J.; Kersten, S. Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptor γ. Mol. Cell. Biol., 2013, 33(7), 1303-1316.
[http://dx.doi.org/10.1128/MCB.00858-12] [PMID: 23339868]
[136]
Nakamura, M.T.; Yudell, B.E.; Loor, J.J. Regulation of energy metabolism by long-chain fatty acids. Prog. Lipid Res., 2014, 53, 124-144.
[http://dx.doi.org/10.1016/j.plipres.2013.12.001] [PMID: 24362249]
[137]
Botta, M.; Audano, M.; Sahebkar, A.; Sirtori, C.; Mitro, N.; Ruscica, M. PPAR agonists and metabolic syndrome: An established role? Int. J. Mol. Sci., 2018, 19(4), 1197.
[http://dx.doi.org/10.3390/ijms19041197] [PMID: 29662003]
[138]
Montaigne, D.; Butruille, L.; Staels, B. PPAR control of metabolism and cardiovascular functions. Nat. Rev. Cardiol., 2021, 18(12), 809-823.
[http://dx.doi.org/10.1038/s41569-021-00569-6] [PMID: 34127848]
[139]
Cook, T.M.; Gavini, C.K.; Jesse, J.; Aubert, G.; Gornick, E.; Bonomo, R.; Gautron, L.; Layden, B.T.; Mansuy-Aubert, V. Vagal neuron expression of the microbiota-derived metabolite receptor, free fatty acid receptor (FFAR3), is necessary for normal feeding behavior. Mol. Metab., 2021, 54, 101350.
[http://dx.doi.org/10.1016/j.molmet.2021.101350] [PMID: 34626852]
[140]
Goswami, C.; Iwasaki, Y.; Yada, T. Short-chain fatty acids suppress food intake by activating vagal afferent neurons. J. Nutr. Biochem., 2018, 57, 130-135.
[http://dx.doi.org/10.1016/j.jnutbio.2018.03.009] [PMID: 29702431]
[141]
Tanida, M.; Yamano, T.; Maeda, K.; Okumura, N.; Fukushima, Y.; Nagai, K. Effects of intraduodenal injection of Lactobacillus johnsonii La1 on renal sympathetic nerve activity and blood pressure in urethane-anesthetized rats. Neurosci. Lett., 2005, 389(2), 109-114.
[http://dx.doi.org/10.1016/j.neulet.2005.07.036] [PMID: 16118039]
[142]
Bravo, J.A.; Forsythe, P.; Chew, M.V.; Escaravage, E.; Savignac, H.M.; Dinan, T.G.; Bienenstock, J.; Cryan, J.F. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. USA, 2011, 108(38), 16050-16055.
[http://dx.doi.org/10.1073/pnas.1102999108] [PMID: 21876150]
[143]
Onyszkiewicz, M.; Gawrys-Kopczynska, M.; Konopelski, P.; Aleksandrowicz, M.; Sawicka, A.; Koźniewska, E.; Samborowska, E.; Ufnal, M. Butyric acid, a gut bacteria metabolite, lowers arterial blood pressure via colon-vagus nerve signaling and GPR41/43 receptors. Pflugers Arch., 2019, 471(11-12), 1441-1453.
[http://dx.doi.org/10.1007/s00424-019-02322-y] [PMID: 31728701]
[144]
Li, Y.; Hao, Y.; Zhu, J.; Owyang, C. Serotonin released from intestinal enterochromaffin cells mediates luminal non–cholecystokininstimulated pancreatic secretion in rats. Gastroenterology, 2000, 118(6), 1197-1207.
[http://dx.doi.org/10.1016/S0016-5085(00)70373-8] [PMID: 10833495]
[145]
Strader, A.D.; Woods, S.C. Gastrointestinal hormones and food intake. Gastroenterology, 2005, 128(1), 175-191.
[http://dx.doi.org/10.1053/j.gastro.2004.10.043] [PMID: 15633135]
[146]
Lal, S.; Kirkup, A.J.; Brunsden, A.M.; Thompson, D.G.; Grundy, D. Vagal afferent responses to fatty acids of different chain length in the rat. Am. J. Physiol. Gastrointest. Liver Physiol., 2001, 281(4), G907-G915.
[http://dx.doi.org/10.1152/ajpgi.2001.281.4.G907] [PMID: 11557510]
[147]
Yuan, H.; Silberstein, S.D. Vagus nerve and vagus nerve stimulation, a comprehensive review: Part I. Headache, 2016, 56(1), 71-78.
[http://dx.doi.org/10.1111/head.12647] [PMID: 26364692]
[148]
Ressler, K.J.; Mayberg, H.S. Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat. Neurosci., 2007, 10(9), 1116-1124.
[http://dx.doi.org/10.1038/nn1944] [PMID: 17726478]
[149]
Hosoi, T.; Okuma, Y.; Matsuda, T.; Nomura, Y. Novel pathway for LPS-induced afferent vagus nerve activation: Possible role of nodose ganglion. Auton. Neurosci., 2005, 120(1-2), 104-107.
[http://dx.doi.org/10.1016/j.autneu.2004.11.012] [PMID: 15919243]
[150]
Bonaz, B.; Sinniger, V.; Pellissier, S. Vagal tone: effects on sensitivity, motility, and inflammation. Neurogastroenterol. Motil., 2016, 28(4), 455-462.
[http://dx.doi.org/10.1111/nmo.12817] [PMID: 27010234]
[151]
Tanimoto, T.; Takeda, M.; Matsumoto, S. Suppressive effect of vagal afferents on cervical dorsal horn neurons responding to tooth pulp electrical stimulation in the rat. Exp. Brain Res., 2002, 145(4), 468-479.
[http://dx.doi.org/10.1007/s00221-002-1138-1] [PMID: 12172658]
[152]
Thurston, C.L.; Randich, A. Quantitative characterization and spinal substrates of antinociception produced by electrical stimulation of the subdiaphragmatic vagus in rats. Pain, 1991, 44(2), 201-209.
[http://dx.doi.org/10.1016/0304-3959(91)90138-N] [PMID: 2052387]
[153]
Erny, D.; Hrabě de Angelis, A.L.; Jaitin, D.; Wieghofer, P.; Staszewski, O.; David, E.; Keren-Shaul, H.; Mahlakoiv, T.; Jakobshagen, K.; Buch, T.; Schwierzeck, V.; Utermöhlen, O.; Chun, E.; Garrett, W.S.; McCoy, K.D.; Diefenbach, A.; Staeheli, P.; Stecher, B.; Amit, I.; Prinz, M. Host microbiota constantly control maturation and function of microglia in the CNS. Nat. Neurosci., 2015, 18(7), 965-977.
[http://dx.doi.org/10.1038/nn.4030] [PMID: 26030851]
[154]
Lupori, L.; Cornuti, S.; Mazziotti, R.; Borghi, E.; Ottaviano, E.; Cas, M.D.; Sagona, G.; Pizzorusso, T.; Tognini, P. The gut microbiota of environmentally enriched mice regulates visual cortical plasticity. Cell Rep., 2022, 38(2), 110212.
[http://dx.doi.org/10.1016/j.celrep.2021.110212] [PMID: 35021093]
[155]
Erny, D.; Dokalis, N.; Mezö, C.; Castoldi, A.; Mossad, O.; Staszewski, O.; Frosch, M.; Villa, M.; Fuchs, V.; Mayer, A.; Neuber, J.; Sosat, J.; Tholen, S.; Schilling, O.; Vlachos, A.; Blank, T.; Gomez de Agüero, M.; Macpherson, A.J.; Pearce, E.J.; Prinz, M. Microbiota-derived acetate enables the metabolic fitness of the brain innate immune system during health and disease. Cell Metab., 2021, 33(11), 2260-2276.e7.
[http://dx.doi.org/10.1016/j.cmet.2021.10.010] [PMID: 34731656]
[156]
Huuskonen, J.; Suuronen, T.; Nuutinen, T.; Kyrylenko, S.; Salminen, A. Regulation of microglial inflammatory response by sodium butyrate and short-chain fatty acids. Br. J. Pharmacol., 2004, 141(5), 874-880.
[http://dx.doi.org/10.1038/sj.bjp.0705682] [PMID: 14744800]
[157]
Liu, J.; Li, H.; Gong, T.; Chen, W.; Mao, S.; Kong, Y.; Yu, J.; Sun, J. Anti-neuroinflammatory effect of short-chain fatty acid acetate against Alzheimer’s disease via upregulating GPR41 and inhibiting ERK/JNK/NF-κB. J. Agric. Food Chem., 2020, 68(27), 7152-7161.
[http://dx.doi.org/10.1021/acs.jafc.0c02807] [PMID: 32583667]
[158]
Matt, S.M.; Allen, J.M.; Lawson, M.A.; Mailing, L.J.; Woods, J.A.; Johnson, R.W. Butyrate and dietary soluble fiber improve neuroinflammation associated with aging in mice. Front. Immunol., 2018, 9, 1832.
[http://dx.doi.org/10.3389/fimmu.2018.01832] [PMID: 30154787]
[159]
Sadler, R.; Cramer, J.V.; Heindl, S.; Kostidis, S.; Betz, D.; Zuurbier, K.R.; Northoff, B.H.; Heijink, M.; Goldberg, M.P.; Plautz, E.J.; Roth, S.; Malik, R.; Dichgans, M.; Holdt, L.M.; Benakis, C.; Giera, M.; Stowe, A.M.; Liesz, A. Short-chain fatty acids improve poststroke recovery via immunological mechanisms. J. Neurosci., 2020, 40(5), 1162-1173.
[http://dx.doi.org/10.1523/JNEUROSCI.1359-19.2019] [PMID: 31889008]
[160]
Wenzel, T.J.; Gates, E.J.; Ranger, A.L.; Klegeris, A. Short-chain fatty acids (SCFAs) alone or in combination regulate select immune functions of microglia-like cells. Mol. Cell. Neurosci., 2020, 105, 103493.
[http://dx.doi.org/10.1016/j.mcn.2020.103493] [PMID: 32333962]
[161]
Li, H.; Xiang, Y.; Zhu, Z.; Wang, W.; Jiang, Z.; Zhao, M.; Cheng, S.; Pan, F.; Liu, D.; Ho, R.C.M.; Ho, C.S.H. Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat. J. Neuroinflammation, 2021, 18(1), 254.
[http://dx.doi.org/10.1186/s12974-021-02303-y] [PMID: 34736493]
[162]
Liu, Q.; Xie, T.; Xi, Y.; Li, L.; Mo, F.; Liu, X.; Liu, Z.; Gao, J.M.; Yuan, T. Sesamol attenuates amyloid peptide accumulation and cognitive deficits in APP/PS1 mice: The mediating role of the gut-brain axis. J. Agric. Food Chem., 2021, 69(43), 12717-12729.
[http://dx.doi.org/10.1021/acs.jafc.1c04687] [PMID: 34669408]
[163]
Hu, L.; Zhu, S.; Peng, X.; Li, K.; Peng, W.; Zhong, Y.; Kang, C.; Cao, X.; Liu, Z.; Zhao, B. High salt elicits brain inflammation and cognitive dysfunction, accompanied by alternations in the gut microbiota and decreased SCFA production. J. Alzheimers Dis., 2020, 77(2), 629-640.
[http://dx.doi.org/10.3233/JAD-200035] [PMID: 32741809]
[164]
Shi, H.; Ge, X.; Ma, X.; Zheng, M.; Cui, X.; Pan, W.; Zheng, P.; Yang, X.; Zhang, P.; Hu, M.; Hu, T.; Tang, R.; Zheng, K.; Huang, X.F.; Yu, Y. A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites. Microbiome, 2021, 9(1), 223.
[http://dx.doi.org/10.1186/s40168-021-01172-0] [PMID: 34758889]
[165]
Calvo-Barreiro, L.; Eixarch, H.; Cornejo, T.; Costa, C.; Castillo, M.; Mestre, L.; Guaza, C.; Martínez-Cuesta, M.C.; Tanoue, T.; Honda, K.; González-López, J.J.; Montalban, X.; Espejo, C. Selected clostridia strains from the human microbiota and their metabolite, butyrate, improve experimental autoimmune encephalomyelitis. Neurotherapeutics, 2021, 18(2), 920-937.
[http://dx.doi.org/10.1007/s13311-021-01016-7] [PMID: 33829410]

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