Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy

Lin, Binbin; Wang, Yuting; Zhang, Haining; Yuan, Yanyan; Zhang, Ying; Chen, Gang

doi:10.1186/s10194-020-01170-x

Cited by 81 publications

(69 citation statements)

References 171 publications

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“…Dysfunction of this bidirectional communication is involved in numerous diseases of the nervous system, such as Parkinson’s disease, Alzheimer's disease, stroke, multiple sclerosis and spinal cord injury [ 9 – 13 ]. Additionally, the gut microbiota has been reported to be a pivotal regulator that directly or indirectly mediates the development of neuropathic pain through a complex network of immune, metabolic, endocrine, and neural signalling pathways [ 14 ]. To date, the specific mechanisms underlying gut microbiota-mediated pain progression remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain

et al. 2021

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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 Helicobacter, Phascolarctobacterium, Christensenella, Blautia, Streptococcus, Rothia and Lactobacillus were significantly increased, whereas the abundances of Ignatzschineria, Butyricimonas, Escherichia, AF12, and Corynebacterium 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.

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Section: Introductionmentioning

confidence: 99%

“…The gut microbiota regulates several metabolic and neurological signalling pathways in the host that can be associated with neuropathic pain [ 14 ]. The spinal dorsal horn (SDH) is the primary centre for the processing and transmission of pain perception and plays an essential role in the initiation and maintenance of neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain

et al. 2021

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“…depression and anxiety), 24 , 32 , 33 Parkinson’s disease, 34 increased hypothalamic pituitary adrenal axis (HPA) activity, 35 systemic lupus erythematosus 36 and systemic inflammation. 37 , 38 And, there is a growing appreciation that the gut microbiome may contribute to chronic extra-abdominal pain states, 1 , 3 – 6 for example in cutaneous inflammatory hyperalgesia 39 and paclitaxel-induced cutaneous thermal and mechanical nociception. 11 However, to the best of our knowledge evaluation of the role of the gut microbiome on skeletal muscle mechanical hyperalgesia has not previously been evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…There is an increasing appreciation that the gastrointestinal (gut) microbiome affects the course and severity of many biological processes and diseases, including pain. [1][2][3][4][5][6] Most studies evaluating the role of the gut microbiome in pain have focused on modulation of visceral pain and hypersensitivity (e.g. preclinical models, as well as in inflammatory bowel disease and colitis), [7][8][9][10] and others have shown that the gut microbiome may affect chemotherapy-induced neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

A role for gut microbiota in early-life stress-induced widespread muscle pain in the adult rat

2021

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Adult rats that experienced neonatal limited bedding (NLB), a form of early-life stress, experience persistent muscle mechanical hyperalgesia. Since there is a growing recognition that the gut microbiome regulates pain and nociception, and that early-life stress produces a long-lasting impact on the gut microbiome, we tested the hypothesis that persistent muscle hyperalgesia seen in adult NLB rats could be ameliorated by interventions that modify the gut microbiome. Adult NLB rats received probiotics, either Lactobacillus rhamnosus GG (10 billion CFU/150 ml) or De Simone Formulation (DSF) (112.5 billion CFU/150 ml mixture of 8 bacterial species), in their drinking water, or non-absorbable antibiotics, rifaximin or neomycin, admixed with cookie dough, to provide 50 mg/kg. Mechanical nociceptive threshold in the gastrocnemius muscle was evaluated before and at several time points after administration of probiotics or antibiotics. Adult NLB rats fed probiotics L. Rhamnosus or DSF, antibiotics, as well as rats fed non-absorbable antibiotics rifaximin or neomycin, had markedly attenuated muscle mechanical hyperalgesia. We hypothesize that persistent skeletal muscle hyperalgesia produced by NLB stress may be, at least in part, due to a contribution of the gut microbiome, and that modulation of gut microbiome using probiotics or non-absorbable antibiotics, may be novel therapeutic approaches for the treatment of chronic musculoskeletal pain.

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“…A key role of the intestinal microbiota in the development of inflammatory pain has been detected by measuring the hypernociceptive responses in germ-free and conventional mice [ 138 ]. Recent evidence supports the significant impact of the gut microbiome on neuropathic pain providing the potential for novel therapeutic strategies [ 139 ]. CIPN and the gut microbiome may be linked via the immune-nervous-endocrine axis [ 140 ].…”

Section: Chemotherapy-induced Dysbiosis Associated With Cognitive mentioning

confidence: 99%

Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity

Ciernikova

Mego

Chovanec

2021

Cancers

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Chemotherapy, targeting not only malignant but also healthy cells, causes many undesirable side effects in cancer patients. Due to this fact, long-term cancer survivors often suffer from late effects, including cognitive impairment and cardiovascular toxicity. Chemotherapy damages the intestinal mucosa and heavily disrupts the gut ecosystem, leading to gastrointestinal toxicity. Animal models and clinical studies have revealed the associations between intestinal dysbiosis and depression, anxiety, pain, impaired cognitive functions, and cardiovascular diseases. Recently, a possible link between chemotherapy-induced gut microbiota disruption and late effects in cancer survivors has been proposed. In this review, we summarize the current understanding of preclinical and clinical findings regarding the emerging role of the microbiome and the microbiota–gut–brain axis in chemotherapy-related late effects affecting the central nervous system (CNS) and heart functions. Importantly, we provide an overview of clinical trials evaluating the relationship between the gut microbiome and cancer survivorship. Moreover, the beneficial effects of probiotics in experimental models and non-cancer patients with neurocognitive disorders and cardiovascular diseases as well as several studies on microbiota modulations via probiotics or fecal microbiota transplantation in cancer patients are discussed.

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Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy

Cited by 81 publications

References 171 publications

Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain

Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain

A role for gut microbiota in early-life stress-induced widespread muscle pain in the adult rat

Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity

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