Erratum: Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

Cl, Li; Li, KC; Wu, Dong‐Dong; Chen, Y; Luo, Hao; Zhao, Xiujian; Ss, Wang; Sun, MM; Lu, Yue; Zhong, Yanqiang; Xy, Hu; Hou, Rui; Zhou, BB; Liu, Bao; Xiao, HS; Zhang, X

doi:10.1038/cr.2016.90

Cited by 104 publications

(102 citation statements)

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“…Reducing CXCR4-mediated nociceptor hyperexcitability reverses painful diabetic neuropathy DRG neuron subtypes are identified using molecular markers (42)(43)(44). Because more than 90% of DRG nociceptors express Na v 1.8 (23), we targeted our studies to this population.…”

Section: Introductionmentioning

confidence: 99%

Reducing CXCR4-mediated nociceptor hyperexcitability reverses painful diabetic neuropathy

Jayaraj¹,

Bhattacharyya²,

Belmadani³

et al. 2018

Journal of Clinical Investigation

110

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Painful diabetic neuropathy (PDN) is an intractable complication of diabetes that affects 25% of patients. PDN is characterized by neuropathic pain and small-fiber degeneration, accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability and loss of their axons within the skin. The molecular mechanisms underlying DRG nociceptor hyperexcitability and small-fiber degeneration in PDN are unknown. We hypothesize that chemokine CXCL12/CXCR4 signaling is central to this mechanism, as we have shown that CXCL12/CXCR4 signaling is necessary for the development of mechanical allodynia, a pain hypersensitivity behavior common in PDN. Focusing on DRG neurons expressing the sodium channel Nav1.8, we applied transgenic, electrophysiological, imaging, and chemogenetic techniques to test this hypothesis. In the high-fat diet mouse model of PDN, we were able to prevent and reverse mechanical allodynia and small-fiber degeneration by limiting CXCR4 signaling or neuronal excitability. This study reveals that excitatory CXCR4/CXCL12 signaling in Nav1.8-positive DRG neurons plays a critical role in the pathogenesis of mechanical allodynia and small-fiber degeneration in a mouse model of PDN. Hence, we propose that targeting CXCR4-mediated DRG nociceptor hyperexcitability is a promising therapeutic approach for disease-modifying treatments for this currently intractable and widespread affliction.

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Section: Introductionmentioning

confidence: 99%

Reducing CXCR4-mediated nociceptor hyperexcitability reverses painful diabetic neuropathy

Jayaraj¹,

Bhattacharyya²,

Belmadani³

et al. 2018

Journal of Clinical Investigation

110

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“…TRPA1 is expressed in a subpopulation of primary sensory neurons of the trigeminal, nodose, and dorsal root ganglia (DRG) [ 40 ]. In DRG, according to a newly-developed cataloging method, expression of TRPA1 was detected in five clusters or subclusters among a total of 14 neuronal subclusters [ 41 ]. These TPRA1-positive neurons participate in pain, thermal and mechanoreceptive sensation [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

“…In DRG, according to a newly-developed cataloging method, expression of TRPA1 was detected in five clusters or subclusters among a total of 14 neuronal subclusters [ 41 ]. These TPRA1-positive neurons participate in pain, thermal and mechanoreceptive sensation [ 41 ]. Isolated mouse DRG neurons were stimulated with malathion and changes in [Ca 2+ ] i were monitored.…”

Section: Resultsmentioning

confidence: 99%

TRPA1 channel mediates organophosphate-induced delayed neuropathy

et al. 2017

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The organophosphate-induced delayed neuropathy (OPIDN), often leads to paresthesias, ataxia and paralysis, occurs in the late-stage of acute poisoning or after repeated exposures to organophosphate (OP) insecticides or nerve agents, and may contribute to the Gulf War Syndrome. The acute phase of OP poisoning is often attributed to acetylcholinesterase inhibition. However, the underlying mechanism for the delayed neuropathy remains unknown and no treatment is available. Here we demonstrate that TRPA1 channel (Transient receptor potential cation channel, member A1) mediates OPIDN. A variety of OPs, exemplified by malathion, activates TRPA1 but not other neuronal TRP channels. Malathion increases the intracellular calcium levels and upregulates the excitability of mouse dorsal root ganglion neurons in vitro. Mice with repeated exposures to malathion also develop local tissue nerve injuries and pain-related behaviors, which resembles OPIDN. Both the neuropathological changes and the nocifensive behaviors can be attenuated by treatment of TRPA1 antagonist HC030031 or abolished by knockout of Trpa1 gene. In the classic hens OPIDN model, malathion causes nerve injuries and ataxia to a similar level as the positive inducer tri-ortho-cresyl phosphate (TOCP), which also activates TRPA1 channel. Treatment with HC030031 reduces the damages caused by malathion or tri-ortho-cresyl phosphate. Duloxetine and Ketotifen, two commercially available drugs exhibiting TRPA1 inhibitory activity, show neuroprotective effects against OPIDN and might be used in emergency situations. The current study suggests TRPA1 is the major mediator of OPIDN and targeting TRPA1 is an effective way for the treatment of OPIDN.

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“…In addition, TRPC5 has been found to be localized to small and medium diameter sensory neurons [65]. A single cell RNA sequencing study also determined a subset of DRG neurons express TRPC subunits [66,67]. Interestingly, the majority of the TRPC3-positive neurons did not show TRPV1 immunoreactivity [57].…”

Section: Trpc Protein Expression In the Drgmentioning

confidence: 99%

Canonical Transient Receptor Potential (TRPC) Channels in Nociception and Pathological Pain

Sun

Chu

et al. 2020

Neural Plasticity

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Chronic pathological pain is one of the most intractable clinical problems faced by clinicians and can be devastating for patients. Despite much progress we have made in understanding chronic pain in the last decades, its underlying mechanisms remain elusive. It is assumed that abnormal increase of calcium levels in the cells is a key determinant in the transition from acute to chronic pain. Exploring molecular players mediating Ca2+ entry into cells and molecular mechanisms underlying activity-dependent changes in Ca2+ signaling in the somatosensory pain pathway is therefore helpful towards understanding the development of chronic, pathological pain. Canonical transient receptor potential (TRPC) channels form a subfamily of nonselective cation channels, which permit the permeability of Ca2+ and Na+ into the cells. Initiation of Ca2+ entry pathways by these channels triggers the development of many physiological and pathological functions. In this review, we will focus on the functional implication of TRPC channels in nociception with the elucidation of their role in the detection of external stimuli and nociceptive hypersensitivity.

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Erratum: Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

Cited by 104 publications

References 0 publications

Reducing CXCR4-mediated nociceptor hyperexcitability reverses painful diabetic neuropathy

Reducing CXCR4-mediated nociceptor hyperexcitability reverses painful diabetic neuropathy

TRPA1 channel mediates organophosphate-induced delayed neuropathy

Canonical Transient Receptor Potential (TRPC) Channels in Nociception and Pathological Pain

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