Role of gut microbiota in neuropathy and neuropathic pain states: A systematic preclinical review

Pane, Katia; Boccella, Serena; Guida, Francesca; Franzese, Monica; Maione, Sabatino; Salvatore, Marco

doi:10.1016/j.nbd.2022.105773

Cited by 26 publications

(17 citation statements)

References 67 publications

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“…Finally, it is well recognized that gut microbiota have a great impact in human health [ 47 , 48 ]. Recent studies have shown that neuropathic pain induced by nerve injury [ 49 , 50 ] or by long-term use of morphine [ 51 ] can lead to gut dysbiosis, by altering the composition of the microbiota [ 52 ], thereby impairing intestinal immune function, promoting neurodegenerative diseases such as Alzheimer and Parkinson [ 48 , 53 , 54 ], and aggravating the pain associated with neurodegenerative disease [ 55 ]. Other studies have also demonstrated that fecal microbiota transplantation and treatments with prebiotics and probiotics are potential therapeutic approaches for Alzheimer [ 56 , 57 ] and Parkinson [ 58 , 59 ], by modifying gut microbiota.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Increases the Analgesic Effects of µ- and δ-Opioid Receptors during Neuropathic Pain: Pathways Implicated

et al. 2022

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Recent studies have revealed that hydrogen sulfide (H2S) increases the analgesic actions of the δ-opioid receptor (DOR) in inflammatory pain. However, the possible improvement of the analgesia of μ-opioid receptor (MOR) and DOR agonists during neuropathic pain, through pretreatment with two slow-releasing H2S donors—DADS (diallyl disulfide) and GYY4137 (morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex)—is still unknown. In male C57BL/6J mice with neuropathic pain incited by chronic constriction of the sciatic nerve (CCI), we evaluated: (1) the influence of DADS (3.5 mg/kg) and GYY4137 (0.7 mg/kg) on the inhibition of the allodynia and hyperalgesia produced by the systemic or local administration of morphine (3 mg/kg or 65 µg) and UFP-512 (1 mg/kg or 12.5 µg); (2) the reversion of the antinociceptive actions of high doses of DADS (30 mg/kg) and GYY4137 (24 mg/kg) with MOR and DOR antagonists; and (3) the effects of H2S donors on oxidative stress, apoptotic responses, and MOR and DOR expression in the medial septum (MS) and dorsal root ganglia (DRG). The results revealed that both DADS and GYY4137 improved the antiallodynic effects of morphine and UFP-512, possibly by up-regulating MOR and DOR expression in DRG. The administration of MOR and DOR antagonists blocked the analgesic properties of DADS and GYY4137, revealing the feasible participation of the endogenous opioid system in H2S analgesic effects. Moreover, both H2S donors inhibited oxidative stress and apoptosis generated by CCI in the MS and/or DRG. This study suggests the co-treatment of H2S donors with MOR or DOR agonists as a potential therapy for neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Increases the Analgesic Effects of µ- and δ-Opioid Receptors during Neuropathic Pain: Pathways Implicated

et al. 2022

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“…Research suggests that increased abundance of Parcubacteria and lower Verrucomicrobia results in neuropathic pain and anhedonia (loss of pleasure) in test rats [ 33 ]. The species Akkermansia muciniphila of the phylum Verrucomicrobia may be associated with pain inhibition [ 34 ]. A. muciniphila also plays a role in controlling immunological function, enhances the synthesis of antimicrobial peptides and improves gut homeostasis [ 35 ].…”

Section: Dysbiosis—imbalance In the Gutmentioning

confidence: 99%

“…The intestinal microbiota also modulates a range of neurotrophins, e.g., brain-derived neurotrophic factor (BDNF) and proteins involved in brain development and plasticity [ 40 ]. GIT dysbiosis can induce local immune activation leading to systemic inflammation, neuroinflammation and changes in CNS functioning [ 34 ]. Activation of neurogenic inflammation via innate immune mechanisms initiates and maintains neuropathic pain as afferent nociceptive nerves communicate with the immune system [ 58 ].…”

Section: Chronic Pain Conditionsmentioning

confidence: 99%

The Association between Dysbiosis and Neurological Conditions Often Manifesting with Chronic Pain

Garvey

2023

Biomedicines

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The prevalence of neurological conditions which manifest with chronic pain is increasing globally, where the World Health Organisation has now classified chronic pain as a risk factor for death by suicide. While many chronic pain conditions have a definitive underlying aetiology, non-somatic conditions represent difficult-to-diagnose and difficult-to-treat public health issues. The interaction of the immune system and nervous system has become an important area in understanding the occurrence of neuroinflammation, nociception, peripheral and central sensitisation seen in chronic pain. More recently, however, the role of the resident microbial species in the human gastrointestinal tract has become evident. Dysbiosis, an alteration in the microbial species present in favour of non-beneficial and pathogenic species has emerged as important in many chronic pain conditions, including functional somatic syndromes, autoimmune disease and neurological diseases. In particular, a decreased abundance of small chain fatty acid, e.g., butyrate-producing bacteria, including Faecalibacterium, Firmicutes and some Bacteroides spp., is frequently evident in morbidities associated with long-term pain. Microbes involved in the production of neurotransmitters serotonin, GABA, glutamate and dopamine, which mediate the gut-brain, axis are also important. This review outlines the dysbiosis present in many disease states manifesting with chronic pain, where an overlap in morbidities is also frequently present in patients.

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“…Despite clinical studies are mostly observational, proofs for a causal role of gut microbiota alterations in pain conditions are provided by a wide number of preclinical studies, as comprehensively reviewed in [34].…”

Section: Pathological Alterations Of Gut-brain Communication: Neurode...mentioning

confidence: 99%

Flavonoids bridging the gut and the brain: Intestinal metabolic fate, and direct or indirect effects of natural supporters against neuroinflammation and neurodegeneration

Magni

Riboldi

Petroni

et al. 2022

Biochemical Pharmacology

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Role of gut microbiota in neuropathy and neuropathic pain states: A systematic preclinical review

Cited by 26 publications

References 67 publications

Hydrogen Sulfide Increases the Analgesic Effects of µ- and δ-Opioid Receptors during Neuropathic Pain: Pathways Implicated

Hydrogen Sulfide Increases the Analgesic Effects of µ- and δ-Opioid Receptors during Neuropathic Pain: Pathways Implicated

The Association between Dysbiosis and Neurological Conditions Often Manifesting with Chronic Pain

Flavonoids bridging the gut and the brain: Intestinal metabolic fate, and direct or indirect effects of natural supporters against neuroinflammation and neurodegeneration

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