Ion channels and neuropathic pain

Klein, Madeleine C; Oaklander, Anne Louise

doi:10.7554/elife.42849

Cited by 8 publications

(7 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6 Even though other ion channels might also be involved, this demonstrated that increased amounts of Gb3 can lead to pathological, physiological, and behavioral signs of neuropathy. 109 Neuron hyperexcitability in DRGs soma has been analyzed in relation to Na v channels. Local anesthetics, block pain via nonselective inhibition of Nav channels in primary afferent nerve fibers of the somatosensory nervous system.…”

Section: Ion Channels and Pain In Fdmentioning

confidence: 99%

See 1 more Smart Citation

Ion channels and pain in Fabry disease

et al. 2021

View full text Add to dashboard Cite

Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A (α-Gal A) activity which results in progressive accumulation of globotriaosylceramide (Gb3) and related metabolites. One prominent feature of Fabry disease is neuropathic pain. Accumulation of Gb3 has been documented in dorsal root ganglia (DRG) as well as other neurons, and has lately been associated with the mechanism of pain though the pathophysiology is still unclear. Small fiber (SF) neuropathy in FD differs from other entities in several aspects related to the perception of pain, alteration of fibers as well as drug therapies used in the practice with patients, with therapies far from satisfying. In order to develop better treatments, more information on the underlying mechanisms of pain is needed. Research in neuropathy has gained momentum from the development of preclinical models where different aspects of pain can be modelled and further analyzed. This review aims at describing the different in vitro and FD animal models that have been used so far, as well as some of the insights gained from their use. We focus especially in recent findings associated with ion channel alterations -that apart from the vascular alterations-, could provide targets for improved therapies in pain.

show abstract

Section: Ion Channels and Pain In Fdmentioning

confidence: 99%

“…6 Even though other ion channels might also be involved, this demonstrated that increased amounts of Gb3 can lead to pathological, physiological, and behavioral signs of neuropathy. 109…”

Section: Ion Channels and Pain In Fdmentioning

confidence: 99%

Ion channels and pain in Fabry disease

et al. 2021

View full text Add to dashboard Cite

show abstract

“…G protein-coupled receptors (GPCRs), ion channels, and lncRNAs are critical in the transmission and modulation of nociceptive information ( Zhao et al, 2013 ; Campbell and Smrcka, 2018 ; Klein and Oaklander, 2018 ). Besides 7–8% of the whole transcriptome that are lncRNAs, about 617, 552, and 598 DEGs were identified as GPCR mRNAs and 257, 253, and 250 DEGs were identified as ion channel mRNAs in the SC, ACC, and AMY, respectively.…”

Section: Resultsmentioning

confidence: 99%

Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Chronic neuropathic pain caused by nerve damage is a most common clinical symptom, often accompanied by anxiety- and depression-like symptoms. Current treatments are very limited at least in part due to incompletely understanding mechanisms underlying this disorder. Changes in gene expression in the dorsal root ganglion (DRG) have been acknowledged to implicate in neuropathic pain genesis, but how peripheral nerve injury alters the gene expression in other pain-associated regions remains elusive. The present study carried out strand-specific next-generation RNA sequencing with a higher sequencing depth and observed the changes in whole transcriptomes in the spinal cord (SC), anterior cingulate cortex (ACC), and amygdala (AMY) following unilateral fourth lumbar spinal nerve ligation (SNL). In addition to providing novel transcriptome profiles of long non-coding RNAs (lncRNAs) and mRNAs, we identified pain- and emotion-related differentially expressed genes (DEGs) and revealed that numbers of these DEGs displayed a high correlation to neuroinflammation and apoptosis. Consistently, functional analyses showed that the most significant enriched biological processes of the upregulated mRNAs were involved in the immune system process, apoptotic process, defense response, inflammation response, and sensory perception of pain across three regions. Moreover, the comparisons of pain-, anxiety-, and depression-related DEGs among three regions present a particular molecular map among the spinal cord and supraspinal structures and indicate the region-dependent and region-independent alterations of gene expression after nerve injury. Our study provides a resource for gene transcript expression patterns in three distinct pain-related regions after peripheral nerve injury. Our findings suggest that neuroinflammation and apoptosis are important pathogenic mechanisms underlying neuropathic pain and that some DEGs might be promising therapeutic targets.

show abstract

“…17,20 Considering hyperexcitability is a hallmark of pain, epilepsy, and anxiety disorders, potassium channels may provide a molecular target to influence neuronal excitability. 39,40 Various plasma membrane and intracellular potassium channels could be pharmacologically targeted to treat pain diseases, [41][42][43][44] such as Piezo2, Nav1.8 and TACAN. 45,46 Kv1.1 channel controls the excitability of neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

miR-155-5p in the spinal cord regulates hypersensitivity in a rat model of bone cancer pain

Liu

Wang

et al. 2022

Mol Pain

View full text Add to dashboard Cite

Background: Noncoding microRNAs have emerged as critical players of gene expression in the nervous system, where they contribute to regulating nervous disease. As stated in previous research, the miR-155-5p upregulation happens in the spinal cord at the nociceptive state. It was unclear if miR-155-5p is linked to bone cancer pain (BCP). Herein, we aimed at investigating the miR-155-5p functional regulatory function in BCP process and delineating the underlying mechanism. Methods: The miRNA-155-5p levels and cellular distribution were determined by RNA sequencing, fluorescent in situ hybridization (FISH), and quantitative real-time PCR (qPCR). Immunoblotting, qPCR, dual-luciferase reporter gene assays, immunofluorescence, recombinant overexpression adeno-associated virus, small interfering RNA, intraspinal administration, and behavioral tests were utilized for exploring the downstream signaling pathway. Results: The miR-155-5p high expression in spinal neurons contributes to BCP maintenance. The miR-155-5p blockage via the intrathecal injection of miR-155-5p antagomir alleviated the pain behavior; in contrast, upregulating miR-155-5p by agomir induced pain hypersensitivity. The miR-155-5p bounds directly to TCF4 mRNA’s 3′ UTR. BCP significantly reduced protein expression of TCF4 versus the Sham group. The miR-155-5p inhibition relieved the spinal TCF4 protein’s down-expression level, while miR-155-5p upregulation by miR-155-5p agomir intrathecal injection decreased TCF4 protein expression in naïve rats. Additionally, TCF4 overexpression in BCP rats could increase Kv1.1. Moreover, TCF4 knockdown inhibited Kv1.1 expression in BCP rats. Indeed, TCF4 and Kv1.1 were co-expressed in BCP spinal cord neurons. Conclusion: The study findings stated the miR-155-5p pivotal role in regulating BCP by directly targeting TCF4 in spinal neurons and suggested that miR-155 could be a promising target in treating BCP.

show abstract

Ion channels and neuropathic pain

Abstract: Pain behaviors in a Fabry mouse model are associated with the accumulation of a fat molecule that disrupts sodium ion channels in small fiber neurons.

Cited by 8 publications

References 9 publications

Ion channels and pain in Fabry disease

Ion channels and pain in Fabry disease

Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury

miR-155-5p in the spinal cord regulates hypersensitivity in a rat model of bone cancer pain

Contact Info

Product

Resources

About