The Regulatory Mechanisms and Therapeutic Potential of MicroRNAs: From Chronic Pain to Morphine Tolerance

The host evolves redundant mechanisms to preserve physiological processing and homeostasis. These functions range from sensing internal and external threats, creating a memory of the insult and generating reflexes, which aim to resolve inflammation. Impairment in such functioning leads to chronic inflammatory diseases. By interacting through a common language of ligands and receptors, the immune and sensory nervous systems work in concert to accomplish such protective functions. Whilst this bidirectional communication helps to protect from danger, it can contribute to disease pathophysiology. Thus, the somatosensory nervous system is anatomically positioned within primary and secondary lymphoid tissues and mucosa to modulate immunity directly. Upstream of this interplay, neurons detect danger, which prompts the release of neuropeptides initiating (i) defensive reflexes (ranging from withdrawal response to coughing) and (ii) chemotaxis, adhesion and local infiltration of immune cells. The resulting outcome of such neuro‐immune interplay is still ill‐defined, but consensual findings start to emerge and support neuropeptides not only as blockers of TH1‐mediated immunity but also as drivers of TH2 immune responses. However, the modalities detected by nociceptors revealed broader than mechanical pressure and temperature sensing and include signals as various as cytokines and pathogens to immunoglobulins and even microRNAs. Along these lines, we aggregated various dorsal root ganglion sensory neuron expression profiling datasets supporting such wide‐ranging sensing capabilities to help identifying new danger detection modalities of these cells. Thus, revealing unexpected aspects of nociceptor neuron biology might prompt the identification of novel drivers of immunity, means to resolve inflammation and strategies to safeguard homeostasis.

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“…Anti‐miRNAs and miRNA mimics might be considered to reverse neuropathic pain (reviewed by Dai et al . ).…”

Section: Endogenous Triggersmentioning

confidence: 97%

“…Therefore, miRNA emerged as a dynamic and endogenous axis of modulating neuronal excitability, independent of their effect on modulating gene expression. Anti-miRNAs and miRNA mimics might be considered to reverse neuropathic pain (reviewed by Dai et al [219]).…”

Section: Exosomementioning

confidence: 99%

Profiling of how nociceptor neurons detect danger – new and old foes

et al. 2019

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“…Although many miRNAs are abnormally expressed in chronic pain and morphine tolerance, few miRNAs overlap. Dai et al (2018) found that only one miRNA (miR-124) was deregulated in microglia in NPP and morphine tolerance. Therefore, miR-124-based treatment is an important potential treatment.…”

Section: Mirnasmentioning

confidence: 99%

Regulatory mechanisms and therapeutic potential of microglial inhibitors in neuropathic pain and morphine tolerance

Fan

Rong

et al. 2020

J. Zhejiang Univ. Sci. B

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Microglia are important cells involved in the regulation of neuropathic pain (NPP) and morphine tolerance. Information on their plasticity and polarity has been elucidated after determining their physiological structure, but there is still much to learn about the role of this type of cell in NPP and morphine tolerance. Microglia mediate multiple functions in health and disease by controlling damage in the central nervous system (CNS) and endogenous immune responses to disease. Microglial activation can result in altered opioid system activity, and NPP is characterized by resistance to morphine. Here we investigate the regulatory mechanisms of microglia and review the potential of microglial inhibitors for modulating NPP and morphine tolerance. Targeted inhibition of glial activation is a clinically promising approach to the treatment of NPP and the prevention of morphine tolerance. Finally, we suggest directions for future research on microglial inhibitors.

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“…miRNAs have emerged as important players in posttranscriptional control of neuronal plasticity (Z. Hu & Li, ). miRNA modulation has also emerged as a new source of possible pain therapeutics (Table ; Dai et al, ; Lopez‐Gonzalez, Landry, & Favereaux, ). For example, knockdown of miRNA 155 has anti‐hyperalgesic effects in a neuropathic pain model (Liu, Zhu, Sun, & Xie, ).…”

Section: Rna Therapeutics Directed Against Mrnamentioning

confidence: 99%

RNA control in pain: Blame it on the messenger

2019

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mRNA function is meticulously controlled. We provide an overview of the integral role that posttranscriptional controls play in the perception of painful stimuli by sensory neurons. These specialized cells, termed nociceptors, precisely regulate mRNA polarity, translation, and stability. A growing body of evidence has revealed that targeted disruption of mRNAs and RNA-binding proteins robustly diminishes pain-associated behaviors. We propose that the use of multiple independent regulatory paradigms facilitates robust temporal and spatial precision of protein expression in response to a range of pain-promoting stimuli.

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The Regulatory Mechanisms and Therapeutic Potential of MicroRNAs: From Chronic Pain to Morphine Tolerance

Cited by 39 publications

References 125 publications

Profiling of how nociceptor neurons detect danger – new and old foes

Profiling of how nociceptor neurons detect danger – new and old foes

Regulatory mechanisms and therapeutic potential of microglial inhibitors in neuropathic pain and morphine tolerance

RNA control in pain: Blame it on the messenger

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