Top

Current Pain and Headache Reports

Published in:

12-02-2024 | Respiratory Microbiota | Chronic Pain Medicine (O Viswanath, Section Editor)

The Gut Microbiota and Chronic Pain

Authors: Ray Pak, Michelle Cho, Keth Pride, Alaa Abd-Elsayed

Published in: Current Pain and Headache Reports | Issue 4/2024

Abstract

Purpose of Review

To examine the effects and interactions between gut microbia and chronic pain.

Recent Findings

The gut microbiome has been an area of interest in both the scientific and general audience due to a growing body of evidence suggesting its influence in a variety of health and disease states. Communication between the central nervous system (CNS) and gut microbiome is said to be bidirectional, in what is referred to as the gut-brain axis.

Summary

Chronic pain is a prevalent costly personal and public health burden and so, there is a vested interest in devising safe and efficacious treatments. Numerous studies, many of which are animal studies, have been conducted to examine the gut microbiome’s role in the pathophysiology of chronic pain states, such as neuropathy, inflammation, visceral pain, etc. As the understanding of this relationship grows, so does the potential for therapeutic targeting of the gut microbiome in chronic pain.

Cresci GA, Bawden E. Gut microbiome: what we do and don’t know. Nutr Clin Pract. 2015;30(6):734–46. https://doi.org/10.1177/0884533615609899. Epub 2015 Oct 8. PMID: 26449893; PMCID: PMC4838018.CrossRefPubMedPubMedCentral

De Luca F, Shoenfeld Y. The microbiome in autoimmune diseases. Clin Exp Immunol. 2019;195(2):74–85. https://doi.org/10.1111/cei.13158. PMID: 29920643; PMCID: PMC6300652.CrossRefPubMed

Appleton J. The gut-brain axis: influence of microbiota on mood and mental health. Integr Med (Encinitas). 2018;17(4):28–32. PMID: 31043907; PMCID: PMC6469458.PubMed

John GK, Mullin GE. The gut microbiome and obesity. Curr Oncol Rep. 2016;18(7):45. https://doi.org/10.1007/s11912-016-0528-7.CrossRefPubMed

Interagency Pain Research Coordinating Committee. National pain strategy: a comprehensive population health-level strategy for pain. Washington, DC: US Department of Health and Human Services, National Institutes of Health; 2016. https://www.iprcc.nih.gov/node/5/national-pain-strategy-report.

Ditre JW, Zale EL, LaRowe LR. A reciprocal model of pain and substance use: transdiagnostic considerations, clinical implications, and future directions. Annu Rev Clin Psychol. 2019;15:503–28. https://doi.org/10.1146/annurev-clinpsy-050718-095440. PMID: 30566371.CrossRefPubMed

Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267–84. https://doi.org/10.1016/j.cell.2009.09.028. PMID: 19837031; PMCID: PMC2852643.CrossRefPubMedPubMedCentral

Chronic Pain Among Adults — United States, 2019–2021. https://www.cdc.gov/mmwr/volumes/72/wr/mm7215a1.htm.

Institute of Medicine (US) Committee on Pain, Disability, and Chronic Illness Behavior, Osterweis M, Kleinman A, Mechanic D. Pain and disability: clinical, behavioral, and public policy perspectives. Washington DC: National Academies Press US; 1987. p. 7. Available from https://www.ncbi.nlm.nih.gov/books/NBK219252/.

10.

Crowell MD. Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br J Pharmacol. 2004;141:1285–93.CrossRefPubMedPubMedCentral

11.

Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota. J Clin Invest. 2015;125:926–38.CrossRefPubMedPubMedCentral

12.

Vandeputte D, Falony G, Vieira-Silva S, Tito RY, Joossens M, Raes J. Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut. 2016;65(1):57–62. https://doi.org/10.1136/gutjnl-2015-309618. Epub 2015 Jun 11. PMID: 26069274; PMCID: PMC4717365.CrossRefPubMed

13.

Houlden A, Goldrick M, Brough D, Vizi ES, Lénárt N, Martinecz B, et al. Brain injury induces specific changes in the caecal microbiota of mice via altered autonomic activity and mucoprotein production. Brain Behav Immun. 2016;57:10–20. https://doi.org/10.1016/j.bbi.2016.04.003. Epub 2016 Apr 6. PMID: 27060191; PMCID: PMC5021180.CrossRefPubMedPubMedCentral

14.

Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by short chain fatty acids. Nutrients. 2011;3(10):858–76. https://doi.org/10.3390/nu3100858. Epub 2011 Oct 14. PMID: 22254083; PMCID: PMC3257741.CrossRefPubMedPubMedCentral

15.

Grabauskas G, Wu X, Gao J, Li JY, Turgeon DK, Owyang C. Prostaglandin E2, produced by mast cells in colon tissues from patients with irritable bowel syndrome, contributes to visceral hypersensitivity in mice. Gastroenterology. 2020;158(8):2195–2207.e6. https://doi.org/10.1053/j.gastro.2020.02.022. Epub 2020 Feb 19. PMID: 32084424; PMCID: PMC7282934.CrossRefPubMed

16.

• Pujo J, De Palma G, Lu J, Galipeau HJ, Surette MG, Collins SM, et al. Gut microbiota modulates visceral sensitivity through calcitonin gene-related peptide (CGRP) production. Gut Microbes. 2023;15(1):2188874. https://doi.org/10.1080/19490976.2023.2188874. Recent and relevant reference.CrossRefPubMedPubMedCentral

17.

•• De Palma G, Shimbori C, Reed DE, Yu Y, Rabbia V, Lu J, et al. Histamine production by the gut microbiota induces visceral hyperalgesia through histamine 4 receptor signaling in mice. Sci Transl Med. 2022;14(655):eabj1895. https://doi.org/10.1126/scitranslmed.abj1895. Recent research in animals.CrossRefPubMed

18.

Janssens Y, Wynendaele E, Verbeke F, Debunne N, Gevaert B, Audenaert K, De Spiegeleer B, et al. Screening of quorum sensing peptides for biological effects in neuronal cells. Peptides. 2018;101:150–6.CrossRefPubMed

19.

Qi J, Buzas K, Fan H, Cohen JI, Wang K, Mont E, et al. Painful pathways induced by TLR stimulation of dorsal root ganglion neurons. J Immunol Baltim Md. 2011;1950(186):6417–6426. https://doi.org/10.4049/jimmunol.1001241. Epub 2011 Apr 22. PMID: 21515789; PMCID: PMC3098909.CrossRef

20.

Luczynski P, Tramullas M, Viola M, Shanahan F, Clarke G, O’Mahony S, et al. Microbiota regulates visceral pain in the mouse. Elife. 2017;6:e25887. https://doi.org/10.7554/eLife.25887. PMID: 28629511; PMCID: PMC5478269.CrossRefPubMedPubMedCentral

21.

Dworsky-Fried Z, Kerr BJ, Taylor AMW. Microbes, microglia, and pain. Neurobiol Pain. 2020;7:100045. https://doi.org/10.1016/j.ynpai.2020.100045. PMID: 32072077; PMCID: PMC7016021.CrossRefPubMedPubMedCentral

22.

Perez-Burgos A, Wang L, McVey Neufeld KA, Mao YK, Ahmadzai M, Janssen LJ, et al. The TRPV1 channel in rodents is a major target for antinociceptive effect of the probiotic Lactobacillus reuteri DSM 17938. J Physiol. 2015;593(17):3943–57. https://doi.org/10.1113/JP270229. Epub 2015 Jul 20. PMID: 26084409; PMCID: PMC4575579.CrossRefPubMedPubMedCentral

23.

Mayer EA, Raybould HE. Role of visceral afferent mechanisms in functional bowel disorders. Gastroenterology. 1990;99:1688–704.CrossRefPubMed

24.

•• Chiu IM, Heesters BA, Ghasemlou N, Von Hehn CA, Zhao F, Tran J, et al. Bacteria activate sensory neurons that modulate pain and inflammation. Nature. 2013;501:52–7. Good article providing understanding of the topic.ADSCrossRefPubMedPubMedCentral

25.

Amaral FA, Sachs D, Costa VV, Fagundes CT, Cisalpino D, Cunha TM, Ferreira SH, Cunha FQ, et al. Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci USA. 2008;105(6):2193–7. https://doi.org/10.1073/pnas.0711891105. Epub 2008 Feb 11. PMID: 18268332; PMCID: PMC2538897.ADSCrossRefPubMedPubMedCentral

26.

Gadotti VM, Martins DF, Pinto HF, et al. Diacerein decreases visceral pain through inhibition of glutamatergic neurotransmission and cytokine signaling in mice. Pharmacol Biochem Behav. 2012;102:549–54. https://doi.org/10.1016/j.pbb.2012.06.018.CrossRefPubMed

27.

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):461–8. https://doi.org/10.1007/s12035-019-01721-7. Epub 2019 Aug 4. PMID: 31378003; PMCID: PMC6980505.CrossRefPubMed

28.

Erny D, Hrabě de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18(7):965–77. https://doi.org/10.1038/nn.4030. Epub 2015 Jun 1. PMID: 26030851; PMCID: PMC5528863.CrossRefPubMedPubMedCentral

29.

Barcelon EE, Cho WH, Jun SB, Lee SJ. Brain microglial activation in chronic pain-associated affective disorder. Front Neurosci. 2019;13:213. https://doi.org/10.3389/fnins.2019.00213. PMID: 30949019; PMCID: PMC6436078.CrossRefPubMedPubMedCentral

30.

Coyle DE. Partial peripheral nerve injury leads to activation of astroglia and microglia which parallels the development of allodynic behavior. Glia. 1998;23(1):75–83 PMID: 9562186.CrossRefPubMed

31.

Ramakrishna C, Corleto J, Ruegger PM, Logan GD, Peacock BB, Mendonca S, 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. PMID: 31889131; PMCID: PMC6937259.ADSCrossRefPubMedPubMedCentral

32.

Gu N, Peng J, Murugan M, Wang X, Eyo UB, Sun D, et al. Spinal microgliosis due to resident microglial proliferation is required for pain hypersensitivity after peripheral nerve injury. Cell Rep. 2016;16(3):605–14. https://doi.org/10.1016/j.celrep.2016.06.018. Epub 2016 Jun 30. PMID: 27373153; PMCID: PMC4956495.CrossRefPubMedPubMedCentral

33.

Guan Z, Kuhn JA, Wang X, Colquitt B, Solorzano C, Vaman S, et al. Injured sensory neuron-derived CSF1 induces microglial proliferation and DAP12-dependent pain. Nat Neurosci. 2016;19(1):94–101. https://doi.org/10.1038/nn.4189. Epub 2015 Dec 7. PMID: 26642091; PMCID: PMC4703328.CrossRefPubMed

34.

McMahon SB, Cafferty WB, Marchand F. Immune and glial cell factors as pain mediators and modulators. Exp Neurol. 2005;192(2):444–62. https://doi.org/10.1016/j.expneurol.2004.11.001. PMID: 15755561.CrossRefPubMed

35.

Watkins LR, Milligan ED, Maier SF. Glial proinflammatory cytokines mediate exaggerated pain states: implications for clinical pain. Adv Exp Med Biol. 2003;521:1–21 PMID: 12617561.PubMed

36.

DeLeo JA, Tanga FY, Tawfik VL. Neuroimmune activation and neuroinflammation in chronic pain and opioid tolerance/hyperalgesia. Neuroscientist. 2004;10(1):40–52. https://doi.org/10.1177/1073858403259950. PMID: 14987447.CrossRefPubMed

37.

Milligan ED, Twining C, Chacur M, Biedenkapp J, O’Connor K, Poole S, et al. Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats. J Neurosci. 2003;23(3):1026–40. https://doi.org/10.1523/JNEUROSCI.23-03-01026.2003. PMID: 12574433; PMCID: PMC6741915.CrossRefPubMedPubMedCentral

38.

Kawasaki Y, Zhang L, Cheng JK, Ji RR. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci. 2008;28(20):5189–94. https://doi.org/10.1523/JNEUROSCI.3338-07.2008. PMID: 18480275; PMCID: PMC2408767.CrossRefPubMedPubMedCentral

39.

Scholz J, Finnerup NB, Attal N, Aziz Q, Baron R, Bennett MI, et al. The IASP classification of chronic pain for ICD-11: chronic neuropathic pain. Pain. 2019;160(1):53–9. https://doi.org/10.1097/j.pain.0000000000001365. PMID: 30586071; PMCID: PMC6310153.CrossRefPubMedPubMedCentral

40.

Chen P, Wang C, Ren YN, Ye ZJ, Jiang C, Wu ZB. Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain. Mol Brain. 2021;14(1):50. https://doi.org/10.1186/s13041-021-00765-y. PMID: 33750430; PMCID: PMC7941960.CrossRefPubMedPubMedCentral

41.

Ellis RJ, Heaton RK, Gianella S, Rahman G, Knight R. Reduced gut microbiome diversity in people with HIV who have distal neuropathic pain. J Pain. 2022;23(2):318–25. https://doi.org/10.1016/j.jpain.2021.08.006. Epub 2021 Sep 13. PMID: 34530155; PMCID: PMC9854399.CrossRefPubMed

42.

Ding W, You Z, Chen Q, Yang L, Doheny J, Zhou X, et al. Gut microbiota influences neuropathic pain through modulating proinflammatory and anti-inflammatory T cells. Anesth Analg. 2021;132(4):1146–55. https://doi.org/10.1213/ANE.0000000000005155. Erratum in: Anesth Analg. 2022 Jul 1;135(1):e10. PMID: 32889847.CrossRefPubMed

43.

Ma P, Mo R, Liao H, Qiu C, Wu G, Yang C, et al. Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve injury, chemotherapy, and diabetes in mice. J Neuroinflammation. 2022;19(1):169. https://doi.org/10.1186/s12974-022-02523-w. PMID: 35764988; PMCID: PMC9237999.CrossRefPubMedPubMedCentral

44.

Shen S, Lim G, You Z, Ding W, Huang P, Ran C, et al. Gut microbiota is critical for the induction of chemotherapy-induced pain. Nat Neurosci. 2017;20(9):1213–6. https://doi.org/10.1038/nn.4606. Epub 2017 Jul 17. PMID: 28714953; PMCID: PMC5575957.CrossRefPubMedPubMedCentral

45.

Pevida M, Lastra A, Hidalgo A, Baamonde A, Menéndez L. Spinal CCL2 and microglial activation are involved in paclitaxel-evoked cold hyperalgesia. Brain Res Bull. 2013;95:21–7. https://doi.org/10.1016/j.brainresbull.2013.03.005. Epub 2013 Apr 2. PMID: 23562605.CrossRefPubMed

46.

Moloney RD, Johnson AC, O’Mahony SM, Dinan TG, Greenwood-Van Meerveld B, Cryan JF. Stress and the microbiota-gut-brain axis in visceral pain: relevance to irritable bowel syndrome. CNS Neurosci Ther. 2016;22(2):102–17. https://doi.org/10.1111/cns.12490. Epub 2015 Dec 10. PMID: 26662472; PMCID: PMC6492884.CrossRefPubMed

47.

Sengupta JN. Visceral pain: the neurophysiological mechanism. Handb Exp Pharmacol. 2009;194:31–74. https://doi.org/10.1007/978-3-540-79090-7_2. PMID: 19655104; PMCID: PMC3156094.CrossRef

48.

Bielefeldt K, Davis B, Binion DG. Pain and inflammatory bowel disease. Inflamm Bowel Dis. 2009;15(5):778–88. https://doi.org/10.1002/ibd.20848. PMID: 19130619; PMCID: PMC3180862.CrossRefPubMed

49.

Distrutti E, Monaldi L, Ricci P, Fiorucci S. Gut microbiota role in irritable bowel syndrome: new therapeutic strategies. World J Gastroenterol. 2016;22(7):2219–41. https://doi.org/10.3748/wjg.v22.i7.2219. PMID: 26900286; PMCID: PMC4734998.CrossRefPubMedPubMedCentral

50.

Kassinen A, Krogius-Kurikka L, Mäkivuokko H, Rinttilä T, Paulin L, Corander J, et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology. 2007;133(1):24–33. https://doi.org/10.1053/j.gastro.2007.04.005. Epub 2007 Apr 14. PMID: 17631127.CrossRefPubMed

51.

Si JM, Yu YC, Fan YJ, Chen SJ. Intestinal microecology and quality of life in irritable bowel syndrome patients. World J Gastroenterol. 2004 Jun 15;10(12):1802–5.

52.

Rajilić-Stojanović M, Biagi E, Heilig HG, Kajander K, Kekkonen RA, Tims S, de Vos WM. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology. 2011;141:1792–801.

53.

Saulnier DM, Riehle K, Mistretta TA, et al. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology. 2011;141:1782–91. https://doi.org/10.1053/j.gastro.2011.06.072.CrossRefPubMed

54.

Mamieva Z, Poluektova E, Svistushkin V, Sobolev V, Shifrin O, Guarner F, et al. Antibiotics, gut microbiota, and irritable bowel syndrome: what are the relations? World J Gastroenterol. 2022;28(12):1204–19. https://doi.org/10.3748/wjg.v28.i12.1204. PMID: 35431513; PMCID: PMC8968486.CrossRefPubMedPubMedCentral

55.

Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157:121–41. https://doi.org/10.1016/j.cell.2014.03.011.CrossRefPubMedPubMedCentral

56.

Esquerre N, Basso L, Defaye M, Vicentini FA, Cluny N, Bihan D, et al. Colitis-induced microbial perturbation promotes postinflammatory visceral hypersensitivity. Cell Mol Gastroenterol Hepatol. 2020;10(2):225–44. https://doi.org/10.1016/j.jcmgh.2020.04.003. Epub 2020 Apr 11. PMID: 32289500; PMCID: PMC7301239.CrossRefPubMedPubMedCentral

57.

Lucarini E, Di Pilato V, Parisio C, Micheli L, Toti A, Pacini A, et al. Visceral sensitivity modulation by faecal microbiota transplantation: the active role of gut bacteria in pain persistence. Pain. 2022;163(5):861–77. https://doi.org/10.1097/j.pain.0000000000002438. PMID: 34393197; PMCID: PMC9009324.CrossRefPubMed

58.

Rizzoli P, Mullally WJ. Headache. Am J Med. 2018;131(1):17–24. https://doi.org/10.1016/j.amjmed.2017.09.005. Epub 2017 Sep 20. PMID: 28939471.CrossRefPubMed

59.

Kang L, Tang W, Zhang Y, Zhang M, Liu J, Li Y, et al. The gut microbiome modulates nitroglycerin-induced migraine-related hyperalgesia in mice. Cephalalgia. 2022;42(6):490–9. https://doi.org/10.1177/03331024211050036. Epub 2021 Oct 13. PMID: 34644194.CrossRefPubMed

60.

Yong D, Lee H, Min HG, Kim K, Oh HS, Chu MK. Altered gut microbiota in individuals with episodic and chronic migraine. Sci Rep. 2023;13(1):626. https://doi.org/10.1038/s41598-023-27586-4. PMID: 36635330; PMCID: PMC9835027.ADSCrossRefPubMedPubMedCentral

61.

Kopchak OO, Hrytsenko OY, Pulyk OR. Peculiarities of the gut microbiota in patients with migraine comparing to healthy individuals. Wiad Lek. 2022;75(9):2218–21. https://doi.org/10.36740/WLek202209207. PMID: 36378698.CrossRefPubMed

62.

He Q, Wang W, Xiong Y, Tao C, Ma L, Ma J, et al. A causal effects of gut microbiota in the development of migraine. J Headache Pain. 2023;24(1):90. https://doi.org/10.1186/s10194-023-01609-x. PMID: 37460956; PMCID: PMC10353251.CrossRefPubMedPubMedCentral

63.

Urita Y, Goto M, Watanabe T, Matsuzaki M, Gomi A, Kano M, et al. Continuous consumption of fermented milk containing Bifidobacterium bifidum YIT 10347 improves gastrointestinal and psychological symptoms in patients with functional gastrointestinal disorders. Biosci Microbiota Food Health. 2015;34(2):37–44. https://doi.org/10.12938/bmfh.2014-017. Epub 2015 Jan 21. PMID: 25918671; PMCID: PMC4405396.CrossRefPubMedPubMedCentral

64.

Guglielmetti S, Mora D, Gschwender M, Popp K. Randomised clinical trial: Bifidobacterium bifidum MIMBb75 significantly alleviates irritable bowel syndrome and improves quality of life–a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011;33(10):1123–32. https://doi.org/10.1111/j.1365-2036.2011.04633.x. Epub 2011 Mar 21. PMID: 21418261.CrossRefPubMed

65.

Andresen V, Gschossmann J, Layer P. Heat-inactivated Bifidobacterium bifidum MIMBb75 (SYN-HI-001) in the treatment of irritable bowel syndrome: a multicentre, randomised, double-blind, placebo-controlled clinical trial. Lancet Gastroenterol Hepatol. 2020;5(7):658–66. https://doi.org/10.1016/S2468-1253(20)30056-X. Epub 2020 Apr 8. PMID: 32277872.CrossRefPubMed

66.

Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, O’Mahony L, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol. 2006;101(7):1581–90. https://doi.org/10.1111/j.1572-0241.2006.00734.x. PMID: 16863564.CrossRefPubMed

67.

O’Mahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128(3):541–51. https://doi.org/10.1053/j.gastro.2004.11.050. PMID: 15765388.CrossRefPubMed

68.

Charbonneau D, Gibb RD, Quigley EM. Fecal excretion of Bifidobacterium infantis 35624 and changes in fecal microbiota after eight weeks of oral supplementation with encapsulated probiotic. Gut Microbes. 2013;4(3):201–11. https://doi.org/10.4161/gmic.24196. Epub 2013 Apr 2. PMID: 23549409; PMCID: PMC3669165.CrossRefPubMedPubMedCentral

69.

Yoon JS, Sohn W, Lee OY, Lee SP, Lee KN, Jun DW, et al. Effect of multispecies probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Gastroenterol Hepatol. 2014;29(1):52–9. https://doi.org/10.1111/jgh.12322. PMID: 23829297.CrossRefPubMed

70.

Sisson G, Ayis S, Sherwood RA, Bjarnason I. Randomised clinical trial a liquid multi-strain probiotic vs. placebo in the irritable bowel syndrome--a 12 week double-blind study. Aliment Pharmacol Ther. 2014;40(1):51–62. https://doi.org/10.1111/apt.12787. Epub 2014 May 11. PMID: 24815298.CrossRefPubMed

71.

Connell M, Shin A, James-Stevenson T, Xu H, Imperiale TF, Herron J. Systematic review and meta-analysis: efficacy of patented probiotic, VSL#3, in irritable bowel syndrome. Neurogastroenterol Motil. 2018;30(12):e13427. https://doi.org/10.1111/nmo.13427. Epub 2018 Aug 1. PMID: 30069978; PMCID: PMC6249050.CrossRefPubMedPubMedCentral

72.

Guandalini S, Magazzù G, Chiaro A, La Balestra V, Di Nardo G, Gopalan S, et al. VSL#3 improves symptoms in children with irritable bowel syndrome: a multicenter, randomized, placebo-controlled, double-blind, crossover study. J Pediatr Gastroenterol Nutr. 2010;51(1):24–30. https://doi.org/10.1097/MPG.0b013e3181ca4d95. PMID: 20453678.CrossRefPubMed

73.

Shulman RJ, Smith EO. Does VSL#3 really improve symptoms in children with IBS? J Pediatr Gastroenterol Nutr. 2012;54(1):109; author reply 109. https://doi.org/10.1097/MPG.0b013e31823df69b. PMID: 22064630; PMCID: PMC4419702.CrossRefPubMedPubMedCentral

74.

Miquel S, Martín R, Lashermes A, Gillet M, Meleine M, Gelot A, et al. Anti-nociceptive effect of Faecalibacterium prausnitzii in non-inflammatory IBS-like models. Sci Rep. 2016;6(1):19399. https://doi.org/10.1038/srep19399. ADSCrossRefPubMedPubMedCentral

75.

Farup PG, Jacobsen M, Ligaarden SC, Rudi K. Probiotics, symptoms, and gut microbiota: what are the relations? A randomized controlled trial in subjects with irritable bowel syndrome. Gastroenterol Res Pract. 2012;2012:214102. https://doi.org/10.1155/2012/214102. Epub 2012 Jul 31. PMID: 22899904; PMCID: PMC3415104.CrossRefPubMedPubMedCentral

76.

Liebregts T, Adam B, Bertel A, Jones S, Schulze J. Effect of E. coli Nissle, 1917 on post-inflammatory visceral sensory function in a rat model. Neurogastroenterol Motility. 2005;17:410–4.CrossRef

77.

Kannampalli P, Pochiraju S, Chichlowski M, Berg BM, Rudolph C. Probiotic Lactobacillus rhamnosus GG (LGG) and prebiotic prevent neonatal inflammation-induced visceral hypersensitivity in adult rats. Neurogastroenterol Motil. 2014;26:1694–704.CrossRefPubMed

78.

Johnson AC, Greenwood-Van Meerveld B, McRorie J. Effects of Bifidobacterium infantis 35624 on post-inflammatory visceral hypersensitivity in the rat. Dig Dis Sci. 2011;56:3179–86.CrossRefPubMed

79.

Martami F, Togha M, Seifishahpar M, Ghorbani Z, Ansari H, Karimi T, et al. The effects of a multispecies probiotic supplement on inflammatory markers and episodic and chronic migraine characteristics: a randomized double-blind controlled trial. Cephalalgia. 2019;39(7):841–53. https://doi.org/10.1177/0333102418820102. Epub 2019 Jan 8. PMID: 30621517.CrossRefPubMed

80.

Bidabadi E, Elyasi M, Hassanzadeh Rad A, Kazemnezhad E. The effect of probiotics on headaches in children with migraine treated with sodium valproate: a randomized controlled clinical trial. Iran J Child Neurol. 2023;17(2):119–26. https://doi.org/10.22037/ijcn.v17i2.40369. Epub 2023 Mar 15. PMID: 37091466; PMCID: PMC10114277.CrossRefPubMedPubMedCentral

81.

de Roos NM, van Hemert S, Rovers JMP, Smits MG, Witteman BJM. The effects of a multispecies probiotic on migraine and markers of intestinal permeability-results of a randomized placebo-controlled study. Eur J Clin Nutr. 2017;71(12):1455–62. https://doi.org/10.1038/ejcn.2017.57. Epub 2017 May 24. PMID: 28537581.CrossRefPubMed

82.

Parohan M, Djalali M, Sarraf P, Yaghoubi S, Seraj A, Foroushani AR, et al. Effect of probiotic supplementation on migraine prophylaxis: a systematic review and meta-analysis of randomized controlled trials. Nutr Neurosci. 2022;25(3):511–8. https://doi.org/10.1080/1028415X.2020.1764292. Epub 2020 May 18. PMID: 32420827.CrossRefPubMed

83.

Ghavami A, Khorvash F, Heidari Z, Khalesi S, Askari G. Effect of synbiotic supplementation on migraine characteristics and inflammatory biomarkers in women with migraine: results of a randomized controlled trial. Pharmacol Res. 2021;169:105668. https://doi.org/10.1016/j.phrs.2021.105668. Epub 2021 May 12. PMID: 33989763.CrossRefPubMed

84.

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;87:455–64. https://doi.org/10.1016/j.bbi.2020.01.016. Epub 2020 Jan 27. PMID: 32001342; PMCID: PMC9444375.CrossRefPubMedPubMedCentral

85.

Staniland AA, Clark AK, Wodarski R, Sasso O, Maione F, D’Acquisto F, et al. Reduced inflammatory and neuropathic pain and decreased spinal microglial response in fractalkine receptor (CX3CR1) knockout mice. J Neurochem. 2010;114(4):1143–57. https://doi.org/10.1111/j.1471-4159.2010.06837.x. Epub 2010 May 28. PMID: 20524966.CrossRefPubMed

86.

Mei XP, Xu H, Xie C, Ren J, Zhou Y, Zhang H, et al. Post-injury administration of minocycline: an effective treatment for nerve-injury induced neuropathic pain. Neurosci Res. 2011;70(3):305–12. https://doi.org/10.1016/j.neures.2011.03.012. Epub 2011 Apr 14. PMID: 21515316.CrossRefPubMed

87.

Ledeboer A, Sloane EM, Milligan ED, Frank MG, Mahony JH, Maier SF, et al. Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain. 2005;115(1–2):71–83. https://doi.org/10.1016/j.pain.2005.02.009. PMID: 15836971.CrossRefPubMed

88.

Mika J, Rojewska E, Makuch W, Przewlocka B. Minocycline reduces the injury-induced expression of prodynorphin and pronociceptin in the dorsal root ganglion in a rat model of neuropathic pain. Neuroscience. 2010;165(4):1420–8. https://doi.org/10.1016/j.neuroscience.2009.11.064. Epub 2009 Dec 1. PMID: 19961904.CrossRefPubMed

89.

Owolabi SA, Saab CY. Fractalkine and minocycline alter neuronal activity in the spinal cord dorsal horn. FEBS Lett. 2006;580(18):4306–10. https://doi.org/10.1016/j.febslet.2006.06.087. Epub 2006 Jul 7. PMID: 16842787.CrossRefPubMed

90.

Raghavendra V, Tanga F, DeLeo JA. Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J Pharmacol Exp Ther. 2003;306(2):624–30. https://doi.org/10.1124/jpet.103.052407. Epub 2003 May 6. PMID: 12734393.CrossRefPubMed

91.

Cho IH, Chung YM, Park CK, Park SH, Lee H, Kim D, et al. Systemic administration of minocycline inhibits formalin-induced inflammatory pain in rat. Brain Res. 2006;1072(1):208–14. https://doi.org/10.1016/j.brainres.2005.12.039. Epub 2006 Jan 19. Erratum in: Brain Res. 2012 Jun 29;1464:89. Li, Hai Ying [corrected to Lee, Haeyeong]. PMID: 16427032.CrossRefPubMed

92.

Hua XY, Svensson CI, Matsui T, Fitzsimmons B, Yaksh TL, Webb M. Intrathecal minocycline attenuates peripheral inflammation-induced hyperalgesia by inhibiting p38 MAPK in spinal microglia. Eur J Neurosci. 2005;22(10):2431–40. https://doi.org/10.1111/j.1460-9568.2005.04451.x. PMID: 16307586.CrossRefPubMed

93.

Sun JS, Yang YJ, Zhang YZ, Huang W, Li ZS, Zhang Y. Minocycline attenuates pain by inhibiting spinal microglia activation in diabetic rats. Mol Med Rep. 2015;12(2):2677–82. https://doi.org/10.3892/mmr.2015.3735. Epub 2015 May 6. PMID: 25955348.CrossRefPubMed

94.

Hains BC, Waxman SG. Activated microglia contribute to the maintenance of chronic pain after spinal cord injury. J Neurosci. 2006;26(16):4308–17. https://doi.org/10.1523/JNEUROSCI.0003-06.2006. PMID: 16624951; PMCID: PMC6674010.CrossRefPubMedPubMedCentral

95.

Shin DA, Kim TU, Chang MC. Minocycline for controlling neuropathic pain: a systematic narrative review of studies in humans. J Pain Res. 2021;14:139–45. https://doi.org/10.2147/JPR.S292824. PMID: 33536779; PMCID: PMC7849188.CrossRefPubMedPubMedCentral

96.

Zhang JD, Liu J, Zhu SW, Fang Y, Wang B, Jia Q, et al. Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation. Acta Pharmacol Sin. 2021;42(11):1821–33. https://doi.org/10.1038/s41401-020-00601-4. Epub 2021 Feb 8. PMID: 33558654; PMCID: PMC8563748.CrossRefPubMedPubMedCentral

97.

Marchand F, Tsantoulas C, Singh D, Grist J, Clark AK, Bradbury EJ, et al. Effects of Etanercept and Minocycline in a rat model of spinal cord injury. Eur J Pain. 2009;13(7):673–81. https://doi.org/10.1016/j.ejpain.2008.08.001. Epub 2008 Oct 11. PMID: 18849175.CrossRefPubMed

98.

Wagner R, Janjigian M, Myers RR. Anti-inflammatory interleukin-10 therapy in CCI neuropathy decreases thermal hyperalgesia, macrophage recruitment, and endoneurial TNF-alpha expression. Pain. 1998;74(1):35–42. https://doi.org/10.1016/S0304-3959(97)00148-6. PMID: 9514558.CrossRefPubMed

99.

Huang Y, Zhu L, Zhang W, Tang Q, Zhong Y. IL-10 alleviates radicular pain by inhibiting TNF-α/p65 dependent Nav1.7 up-regulation in DRG neurons of rats. Brain Res. 2022;1791:147997. https://doi.org/10.1016/j.brainres.2022.147997. Epub 2022 Jun 30. PMID: 35779581.CrossRefPubMed

100.

Li C, Deng T, Shang Z, Wang D, Xiao Y. Blocking TRPA1 and TNF-α signal improves bortezomib-induced neuropathic pain. Cell Physiol Biochem. 2018;51(5):2098–110. https://doi.org/10.1159/000495828. Epub 2018 Dec 6. PMID: 30522101.CrossRefPubMed

101.

Hess A, Axmann R, Rech J, Finzel S, Heindl C, Kreitz S, et al. Blockade of TNF-α rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci USA. 2011;108(9):3731–6. https://doi.org/10.1073/pnas.1011774108. Epub 2011 Jan 18. PMID: 21245297; PMCID: PMC3048151.ADSCrossRefPubMedPubMedCentral

102.

Li Y, Zhang Y, Liu DB, Liu HY, Hou WG, Dong YS. Curcumin attenuates diabetic neuropathic pain by downregulating TNF-α in a rat model. Int J Med Sci. 2013;10(4):377–81. https://doi.org/10.7150/ijms.5224. Epub 2013 Feb 20. PMID: 23471081; PMCID: PMC3590595.CrossRefPubMedPubMedCentral

103.

Yang L, Cao C, Kantor ED, et al. Trends in sedentary behavior among the US population, 2001–2016. JAMA. 2019;321(16):1587–97. https://doi.org/10.1001/jama.2019.3636.CrossRefPubMedPubMedCentral

104.

Malfliet A, Quiroz Marnef A, Nijs J, Clarys P, Huybrechts I, Elma Ö, et al. Obesity hurts: the why and how of integrating weight reduction with chronic pain management. Phys Ther. 2021;101(11):pzab198. https://doi.org/10.1093/ptj/pzab198. PMID: 34403478.CrossRefPubMed

105.

Singh GK, Kim IE, Girmay M, Perry C, Daus GP, Vedamuthu IP, et al. Opioid epidemic in the United States: empirical trends, and a literature review of social determinants and epidemiological, pain management, and treatment patterns. Int J Mch Aids. 2019;8(2):89–100. https://doi.org/10.21106/ijma.284. Epub 2019 Aug 8. PMID: 31723479; PMCID: PMC6804319.CrossRefPubMedPubMedCentral

106.

Mailing LJ, Allen JM, Buford TW, Fields CJ, Woods JA. Exercise and the gut microbiome: a review of the evidence, potential mechanisms, and implications for human health. Exerc Sport Sci Rev. 2019;47(2):75–85. https://doi.org/10.1249/JES.0000000000000183. PMID: 30883471.CrossRefPubMed

107.

Medawar E, Haange SB, Rolle-Kampczyk U, et al. Gut microbiota link dietary fiber intake and short-chain fatty acid metabolism with eating behavior. Transl Psychiatry. 2021;11:500. https://doi.org/10.1038/s41398-021-01620-3.CrossRefPubMedPubMedCentral

108.

Capuco A, Urits I, Hasoon J, Chun R, Gerald B, Wang JK, et al. Current perspectives on gut microbiome dysbiosis and depression. Adv Ther. 2020;37(4):1328–46. https://doi.org/10.1007/s12325-020-01272-7. Epub 2020 Mar 4. PMID: 32130662; PMCID: PMC7140737.CrossRefPubMedPubMedCentral

Title: The Gut Microbiota and Chronic Pain
Authors: Ray Pak
Michelle Cho
Keth Pride
Alaa Abd-Elsayed
Publication date: 12-02-2024
Publisher: Springer US
Keywords: Respiratory Microbiota
Migraine
Neuropathic Pain
Irritable Bowel Syndrome
Published in: Current Pain and Headache Reports / Issue 4/2024
Print ISSN: 1531-3433
Electronic ISSN: 1534-3081
DOI: https://doi.org/10.1007/s11916-024-01221-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The Gut Microbiota and Chronic Pain

Abstract

Purpose of Review

Recent Findings

Summary

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 4/2024

Treatment Options for Posttraumatic Headache: A Current Review of the Literature

Managing trigeminal postherpetic neuralgia

Does weather trigger migraine?

Efficacy and Safety of Ketamine-Dexmedetomidine Versus Ketamine-Propofol Combination for Periprocedural Sedation: A Systematic Review and Meta-analysis

Influences of Genetic and Environmental Factors on Chronic Migraine: A Narrative Review

The Diagnostic Value of Carnett’s Test with Chronic Abdominal Pain: A Narrative Review