Non-coding RNAs in neuropathic pain

Kalpachidou, Theodora; Kummer, Kai K.; Kress, Michaela

doi:10.1042/ns20190099

Cited by 35 publications

(34 citation statements)

References 208 publications

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“…Whether the differential miRNAs and circRNAs were located within nerve endings, skin immune cells or extracellular space is unclear. Importantly, recent mounting literature has suggested that ncRNAs may act as 'master switches' in regulating the neuroimmune balance within the skin (183,184). Further investigation into ncRNA function may present exciting diagnostic and treatment applications for neuropathic pain states.…”

Section: Viral Disease-induced Neuropathymentioning

confidence: 99%

Cutaneous Neuroimmune Interactions in Peripheral Neuropathic Pain States

2021

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Bidirectional interplay between the peripheral immune and nervous systems plays a crucial role in maintaining homeostasis and responding to noxious stimuli. This crosstalk is facilitated by a variety of cytokines, inflammatory mediators and neuropeptides. Dysregulation of this delicate physiological balance is implicated in the pathological mechanisms of various skin disorders and peripheral neuropathies. The skin is a highly complex biological structure within which peripheral sensory nerve terminals and immune cells colocalise. Herein, we provide an overview of the sensory innervation of the skin and immune cells resident to the skin. We discuss modulation of cutaneous immune response by sensory neurons and their mediators (e.g., nociceptor-derived neuropeptides), and sensory neuron regulation by cutaneous immune cells (e.g., nociceptor sensitization by immune-derived mediators). In particular, we discuss recent findings concerning neuroimmune communication in skin infections, psoriasis, allergic contact dermatitis and atopic dermatitis. We then summarize evidence of neuroimmune mechanisms in the skin in the context of peripheral neuropathic pain states, including chemotherapy-induced peripheral neuropathy, diabetic polyneuropathy, post-herpetic neuralgia, HIV-induced neuropathy, as well as entrapment and traumatic neuropathies. Finally, we highlight the future promise of emerging therapies associated with skin neuroimmune crosstalk in neuropathic pain.

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Section: Viral Disease-induced Neuropathymentioning

confidence: 99%

Cutaneous Neuroimmune Interactions in Peripheral Neuropathic Pain States

2021

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“…As master regulators of pain gene expression, miRNAs have emerged as critical pain modulators 14,15 . miR-544-3p is widely expressed in a variety of cell types and has been implicated in multiple physiological and pathological processes, such as cancer, stroke and cardiovascular disease 37,39,40 .…”

Section: Discussionmentioning

confidence: 99%

“…Primary sensory neurons with cell bodies in trigeminal ganglia or dorsal root ganglia (DRG) represent the primary origin of nociception, and are involved in both initiation and maintenance of pathological pain states 13 . Growing evidence suggests that miRNAs expressed in the DRG function as crucial pain modulators via the regulation of pain associated genes 14,15 . miRNA cluster miR-17-92 (including miR-17, miR-18, miR-19a, miR-19b and miR-92) were upregulated in the DRG in neuropathic pain models and in turn down-regulated potassium channels including Kcna1, Kcna4, Kcnc4, Kcnd3 and Kcnq5 16 .…”

Section: Introductionmentioning

confidence: 99%

miR-544-3p mediates arthritis pain through regulation of FcγRI

Liu

Jeon

2021

Preprint

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Chronic or episodic joint pain is a major symptom in rheumatoid arthritis (RA) and its adequate treatment represents an unmet medical need. However, the cellular and molecular mechanisms underlying RA pain remain elusive. Non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of RA as negative regulators of the stability or translation of specific target mRNAs. Yet, their significance in RA pain is still not well defined. We and other groups recently identified neuronally expressed FcγRI as a key driver of arthritis pain in mouse RA models. Thus, we tested the hypothesis that miRNAs that target and regulate neuronal FcγRI attenuate RA pain. Here, we show that miR-544-3p was robustly downregulated whereas FcγRI was significantly upregulated in the dorsal root ganglion (DRG) in mouse RA models. Intrathecal injection of miR-544-3p mimic attenuated established mechanical and heat hyperalgesia in a mouse model of collagen II-induced arthritis (CIA). Moreover, this effect was likely mediated, at least in part, by FcγRI since miR-544-3p mimic downregulated FcγRI in the DRG during arthritis and genetic deletion of FcγRI produced similar antihyperalgesic effects in the CIA model. This notion was further supported by a dual luciferase assay showing that miR-544-3p targeted FcγRI by directly binding to its 3’UTR. In addition, FcγRI expression in DRG neurons in vitro was downregulated by miR-544-3p mimic and upregulated by miR-544-3p inhibitor. In naïve mice, miR-544-3p mimic alleviated acute joint pain hypersensitivity induced by IgG immune complex (IgG-IC), whereas miR-544-3p inhibitor potentiated the pro-nociceptive behavioral effect of IgG-IC. These findings suggest that miR-544-3p causally participates in the maintenance of arthritis pain by targeting neuronal FcγRI, and thus define miR-544-3p as a new potential therapeutic target for treating RA pain.

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“…At present, many miRNAs have been reported in neurodegenerative diseases (22), cancer (23,24), bowel disease (25), and diabetic heart disease (DHD) (26). Although some lncRNAs (27,28) and miRNAs (29,30) have been reported in NP, there are still few reports on how lncRNAs, miRNAs and mRNAs jointly regulate the pathogenesis of NP. Zhou and colleagues (5) analyzed the expression pro le of non-coding RNAs in the spinal cord following spared nerve injury-induced NP by sequencing, and constructed lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks in NP.…”

Section: Discussionmentioning

confidence: 99%

“…Herein, we constructed the lncRNA-mRNA-miRNA network in NP. The lncRNAs can be used as candidate indicators for NP (30). Various studies have provided new mechanisms for the molecular roles of miRNAs in the pathogenesis of NP (37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of the regulatory lncRNA-miRNA-mRNA network in patients with neuropathic pain and prediction of potential therapeutics

Zhang¹,

Liu²,

Song³

et al. 2020

Preprint

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Background: Neuropathic pain (NP) is the main form of chronic pain, caused by damage to the nervous system and dysfunction. Here, we aimed at exploring the key molecules involved in NP pathogenesis via the identification of its regulatory lncRNA-miRNA-mRNA network.Methods: We downloaded NP-related data from public databases and identified differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs through differential gene expression analysis. The lncRNA and miRNA target predictions were performed and an integration of the three datasets was used for construction of the lncRNA-miRNA-mRNA network. Subsequently, functional enrichment analysis and protein-protein interaction (PPI) analysis were performed to explore the role and the interactions of the mRNAs. The drug prediction was performed based on the mRNAs in the lncRNA-miRNA-mRNA network. Results: A total of 8,251 differentially expressed mRNAs (4,193 upregulated and 4,058 downregulated), 959 differentially expressed miRNAs (455 upregulated and 504 downregulated), 2,848 differentially expressed lncRNAs (1,324 upregulated and 1,524 downregulated) were identified by integrating the results of the three microarray datasets. We found that differentially expressed mRNAs were mainly enriched in blood circulation, metal ion transmembrane transporter activity, and synaptic membrane. The most significant pathway of mRNAs in lncRNA-miRNA-mRNA network were GTPase, cell cycle, and platelet activation. A total of 1,200 drugs were predicted as potential therapeutics for NP based on the regulatory genes.Conclusion: Our study predicted drugs that may be effective for NP based on the NP regulatory network. This information will help further reveal the pathological mechanism of NP and provide more treatment options for NP patients.

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Non-coding RNAs in neuropathic pain

Cited by 35 publications

References 208 publications

Cutaneous Neuroimmune Interactions in Peripheral Neuropathic Pain States

Cutaneous Neuroimmune Interactions in Peripheral Neuropathic Pain States

miR-544-3p mediates arthritis pain through regulation of FcγRI

Bioinformatics analysis of the regulatory lncRNA-miRNA-mRNA network in patients with neuropathic pain and prediction of potential therapeutics

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