Neuropathic Pain: From Mechanisms to Treatment

Physiological Reviews, Год журнала: 2020, Номер 101(1), С. 259 - 301

Опубликована: Июнь 25, 2020

Neuropathic pain caused by a lesion or disease of the somatosensory nervous system is common chronic condition with major impact on quality life. Examples include trigeminal neuralgia, painful polyneuropathy, postherpetic and central poststroke pain. Most patients complain an ongoing intermittent spontaneous of, for example, burning, pricking, squeezing quality, which may be accompanied evoked pain, particular to light touch cold. Ectopic activity in, nerve-end neuroma, compressed nerves nerve roots, dorsal root ganglia, thalamus in different conditions underlie Evoked spread neighboring areas, underlying pathophysiology involves peripheral sensitization. Maladaptive structural changes number cell-cell interactions molecular signaling sensitization nociceptive pathways. These alteration ion channels, activation immune cells, glial-derived mediators, epigenetic regulation. The classes therapeutics drugs acting α 2 δ subunits calcium sodium descending modulatory inhibitory

Язык: Английский

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Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Март 8, 2021

Abstract Distinct types of dorsal root ganglion sensory neurons may have unique contributions to chronic pain. Identification primate neuron is critical for understanding the cellular origin and heritability However, molecular insights into are missing. Here we classify non-human based on their transcriptome map human pain neuronal types. First, identified cell correlates between two major datasets mouse Machine learning exposes an overall cross-species conservation somatosensory mouse, although with differences at individual gene level, highlighting importance data clinical translation. We genomic loci associated in onto identify Genome-wide associations converge different distributed disorders that display genetic susceptibilities, suggesting both shared mechanisms conditions.

Язык: Английский

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Single-cell transcriptomic analysis of somatosensory neurons uncovers temporal development of neuropathic pain

Cell Research, Год журнала: 2021, Номер 31(8), С. 904 - 918

Опубликована: Март 10, 2021

Peripheral nerve injury could lead to chronic neuropathic pain. Understanding transcriptional changes induced by provide fundamental insights into the complex pathogenesis of Gene expression profiles dorsal root ganglia (DRG) in pain condition have been studied. However, little is known about transcriptomic individual DRG neurons after peripheral injury. Here we performed single-cell RNA sequencing on dissociated mouse cells spared (SNI). In addition neuron types that are found under physiological conditions, identified three SNI-induced neuronal clusters (SNIICs) characterized Atf3/Gfra3/Gal (SNIIC1), Atf3/Mrgprd (SNIIC2) and Atf3/S100b/Gal (SNIIC3). These SNIICs originated from Cldn9+/Gal+, Mrgprd+ Trappc3l+ neurons, respectively. Interestingly, SNIIC2 switched SNIIC1 increasing Gal reducing Mrgprd 2 days Inferring gene regulatory networks injury, revealed activated transcription factors Atf3 Egr1 enhance while Cpeb1 might suppress within SNI. Furthermore, mined development identify potential analgesic targets. We cardiotrophin-like cytokine factor 1, which activates astrocytes horn spinal cord, was upregulated contributed mechanical allodynia. Therefore, our results a new landscape understand dynamic course type their underlying molecular mechanisms during

Язык: Английский

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Distinct thalamocortical circuits underlie allodynia induced by tissue injury and by depression-like states

Nature Neuroscience, Год журнала: 2021, Номер 24(4), С. 542 - 553

Опубликована: Март 8, 2021

Язык: Английский

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Joint European Academy of Neurology–European Pain Federation–Neuropathic Pain Special Interest Group of the International Association for the Study of Pain guidelines on neuropathic pain assessment

European Journal of Neurology, Год журнала: 2023, Номер 30(8), С. 2177 - 2196

Опубликована: Май 30, 2023

Abstract Background and Purpose In these guidelines, we aimed to develop evidence‐based recommendations for the use of screening questionnaires diagnostic tests in patients with neuropathic pain (NeP). Methods We systematically reviewed studies providing information on sensitivity specificity questionnaires, quantitative sensory testing, neurophysiology, skin biopsy, corneal confocal microscopy. also analysed how functional neuroimaging, peripheral nerve blocks, genetic testing might provide useful diagnosing NeP. Results Of Douleur Neuropathique en 4 Questions (DN4), I‐DN4 (self‐administered DN4), Leeds Assessment Neuropathic Symptoms Signs (LANSS) received a strong recommendation, S‐LANSS LANSS) PainDETECT weak their pathway possible devised recommendation biopsy nociceptive evoked potentials NeP diagnosis. Trigeminal reflex secondary trigeminal neuralgia. Although many support usefulness microscopy neuropathy, no study specifically investigated accuracy this technique Functional neuroimaging blocks are helpful disclosing pathophysiology and/or predicting outcomes, but current literature does not Genetic may be considered at specialist centres, selected cases. Conclusions These clinical practice guidelines Due poor‐to‐moderate quality evidence identified by review, future large‐scale, well‐designed, multicentre assessing needed.

Язык: Английский

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Terahertz wave alleviates comorbidity anxiety in pain by reducing the binding capacity of nanostructured glutamate molecules to GluA2

Research, Год журнала: 2024, Номер 7

Опубликована: Янв. 1, 2024

Comorbid anxiety in chronic pain is clinically common, with a comorbidity rate of over 50%. The main treatments are based on pharmacological, interventional, and implantable approaches, which have limited efficacy carry risk side effects. Here, we report terahertz (THz, 10 12 Hz) wave stimulation (THS) technique, exerts nonthermal, long-term modulatory effects neuronal activity by reducing the binding between nano-sized glutamate molecules GluA2, leading to relief comorbid anxiety-like behaviors mice. In mice co-occurring induced complete Freund’s adjuvant (CFA) injection, hyperactivity was observed glutamatergic neurons anterior cingulate cortex (ACC Glu ). Using whole-cell recording ACC slices, demonstrated that THS (34 THz) effectively inhibited excitability . Moreover, molecular dynamics simulations showed reduced number hydrogen bonds bound GluA2. Furthermore, target CFA-treatment suppressed and, as result, alleviated behaviors. Consistently, inhibition chemogenetics mimics THS-induced antinociceptive antianxiety behavior. Together, our study provides evidence for an intervention technique modulating viable clinical treatment strategy anxiety.

Язык: Английский

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Long-lasting analgesia via targeted in situ repression of Na _V 1.7 in mice

Science Translational Medicine, Год журнала: 2021, Номер 13(584)

Опубликована: Март 10, 2021

Current treatments for chronic pain rely largely on opioids despite their substantial side effects and risk of addiction. Genetic studies have identified in humans key targets pivotal to nociceptive processing. In particular, a hereditary loss-of-function mutation Na

Язык: Английский

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Animal models of pain: Diversity and benefits

Journal of Neuroscience Methods, Год журнала: 2020, Номер 348, С. 108997 - 108997

Опубликована: Ноя. 11, 2020

Язык: Английский

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GPR151 in nociceptors modulates neuropathic pain via regulating P2X3 function and microglial activation

Brain, Год журнала: 2021, Номер 144(11), С. 3405 - 3420

Опубликована: Июль 5, 2021

Neuropathic pain is a major health problem that affects up to 7-10% of the population worldwide. Currently, neuropathic difficult treat because its elusive mechanisms. Here we report orphan G protein-coupled receptor 151 (GPR151) in nociceptive sensory neurons controls induced by nerve injury. GPR151 was mainly expressed non-peptidergic C-fibre dorsal root ganglion and highly upregulated after Importantly, conditional knockout Gpr151 adult significantly alleviated chronic constriction injury-induced pain-like behaviour but did not affect basal nociception. Moreover, DRG required for neuronal hyperexcitability upregulation colony-stimulating factor 1 (CSF1), which necessary microglial activation spinal cord Mechanistically, coupled with P2X3 ion channels promoted their functional activities hypersensitivity. Knockout suppressed P2X3-mediated calcium elevation spontaneous injury mice. Conversely, overexpression enhanced excitability. Furthermore, knockdown ganglia reversed CSF1 upregulation, behaviour. Finally, coexpression confirmed small-diameter human neurons, indicating clinical relevance our findings. Together, results indicate plays key role pathogenesis could be potential target treating pain.

Язык: Английский

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Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets

Frontiers in Pain Research, Год журнала: 2021, Номер 2

Опубликована: Дек. 13, 2021

The persistence of increased excitability and spontaneous activity in injured peripheral neurons is imperative for the development many forms neuropathic pain. This aberrant involves and/or expression voltage-gated Na

Язык: Английский

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