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

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jussi Kupari ◽  
Dmitry Usoskin ◽  
Marc Parisien ◽  
Daohua Lou ◽  
Yizhou Hu ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Sensory Neuron ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Species Conservation ◽  
Cell Types ◽  
Individual Gene ◽  
Cellular Origin ◽  
Neuronal Types

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

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

2020 ◽  
Author(s):  
Jussi Kupari ◽  
Dmitry Usoskin ◽  
Daohua Lou ◽  
Marc Parisien ◽  
Yizhou Hu ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Sensory Neuron ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Species Conservation ◽  
Cell Types ◽  
Individual Gene ◽  
Cellular Origin ◽  
Neuronal Types

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

Dorsal Root Ganglion Neuron Types and Their Functional Specialization

2018 ◽  
pp. 127-155 ◽  
Author(s):  
Edward C. Emery ◽  
Patrik Ernfors
Keyword(s):  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Drg Neurons ◽  
Low Threshold

Primary sensory neurons of the dorsal root ganglion (DRG) respond and relay sensations that are felt, such as those for touch, pain, temperature, itch, and more. The ability to discriminate between the various types of stimuli is reflected by the existence of specialized DRG neurons tuned to respond to specific stimuli. Because of this, a comprehensive classification of DRG neurons is critical for determining exactly how somatosensation works and for providing insights into cell types involved during chronic pain. This article reviews the recent advances in unbiased classification of molecular types of DRG neurons in the perspective of known functions as well as predicted functions based on gene expression profiles. The data show that sensory neurons are organized in a basal structure of three cold-sensitive neuron types, five mechano-heat sensitive nociceptor types, four A-Low threshold mechanoreceptor types, five itch-mechano-heat–sensitive nociceptor types and a single C–low-threshold mechanoreceptor type with a strong relation between molecular neuron types and functional types. As a general feature, each neuron type displays a unique and predicable response profile; at the same time, most neuron types convey multiple modalities and intensities. Therefore, sensation is likely determined by the summation of ensembles of active primary afferent types. The new classification scheme will be instructive in determining the exact cellular and molecular mechanisms underlying somatosensation, facilitating the development of rational strategies to identify causes for chronic pain.

scholarly journals Accumulation of Misfolded SOD1 in Dorsal Root Ganglion Degenerating Proprioceptive Sensory Neurons of Transgenic Mice with Amyotrophic Lateral Sclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Javier Sábado ◽  
Anna Casanovas ◽  
Olga Tarabal ◽  
Marta Hereu ◽  
Lídia Piedrafita ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Ventral Horn ◽  
Spinal Cord Dorsal Horn ◽  
Spinal Cord Dorsal ◽  
Neuronal Types ◽  
Misfolded Sod1 ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease affecting upper and lower motoneurons (MNs). Although the motor phenotype is a hallmark for ALS, there is increasing evidence that systems other than the efferent MN system can be involved. Mutations ofsuperoxide dismutase 1(SOD1) gene cause a proportion of familial forms of this disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a noncell autonomous manner, as evidenced in studies using transgenic mouse models. Here, we used theSOD1G93Amouse model for ALS to detect, by means of conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated neurotoxicity extended to neuronal types other than MNs. We report that large dorsal root ganglion (DRG) proprioceptive neurons accumulate misfolded SOD1 and suffer a degenerative process involving the inflammatory recruitment of macrophagic cells. Degenerating sensory axons were also detected in association with activated microglial cells in the spinal cord dorsal horn of diseased animals. As large proprioceptive DRG neurons project monosynaptically to ventral horn MNs, we hypothesise that a prion-like mechanism may be responsible for the transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory neurons.

scholarly journals Quantitative Sensory Testing of Spinal Cord and Dorsal Root Ganglion Stimulation in Chronic Pain Patients

2021 ◽  
Author(s):  
Vishwanath Sankarasubramanian ◽  
Srinivas Chiravuri ◽  
Ehsan Mirzakhalili ◽  
Carlos J. Anaya ◽  
John Ryan Scott ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Quantitative Sensory Testing ◽  
Sensory Testing ◽  
Chronic Pain Patients ◽  
Pain Patients

scholarly journals ATP metabolizing enzymes ENPP1, 2 and 3 are localized in sensory neurons of rat dorsal root ganglion

2018 ◽  
Author(s):  
Kentaro Nishida ◽  
Yuka Nomura ◽  
Kanako Kawamori ◽  
Akihiro Ohishi ◽  
Kazuki Nagasawa
Keyword(s):  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Adenine Nucleotide ◽  
Expression Profiles ◽  
Critical Role ◽  
Immunohistochemical Analysis ◽  
Uptake System ◽  
Nucleoside Transporter ◽  
Drg Neurons

In dorsal root ganglion (DRG) neurons, ATP is an important neurotransmitter in nociceptive signaling through P2 receptors (P2Rs) such as P2X2/3R, and adenosine is also involved in anti-nociceptive signaling through adenosine A1R. Thus, the clearance system for adenine nucleotide/nucleoside plays a critical role in regulation of nociceptive signaling, but there is little information on it, especially ectoenzyme expression profiles in DRG. In this study, we examined expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterases (ENPPs), by which ATP is metabolized to AMP, in rat DRG. The mRNA expression levels of ENPP2 were greater than those of ENPP1 and ENPP3 in rat DRGs. On immunohistochemical analysis, ENPP1, 2 and 3 were found in soma of DRG neurons. Immunopositive rate of ENPP3 was greater than that of ENPP1 and ENPP2 in all DRG neurons. ENPP3, as compared with ENPP1 and ENPP2, was expressed mainly by isolectin B4-positive cells, and slightly by neurofilament 200-positive ones. In this way, the expression profile of ENPP1, 2 and 3 was different in DRGs, and they were mainly expressed in small/medium-sized DRG neurons. Moreover, ENPP1-, 2- and 3-immunoreactivities were colocalized with P2X2R, P2X3R and prostatic acid phosphatase (PAP), as an ectoenzyme for metabolism from AMP to adenosine. Additionally, PAP-immunoreactivity was colocalized with equilibrative nucleoside transporter (ENT) 1, as an adenosine uptake system. These results suggest that the clearance system consisted of ENPPs, PAP and ENT1 plays an important role in regulation of nociceptive signaling in sensory neurons.

scholarly journals Cytotoxic Effect of Commercially Available Methylprednisolone Acetate with and without Reduced Preservatives on Dorsal Root Ganglion Sensory Neurons in Rats

2014 ◽  
Vol 5;17 (5;9) ◽  
pp. E609-E618
Author(s):  
Nebojsa N. Knezevic
Keyword(s):  
Polyethylene Glycol ◽  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Cytotoxic Effect ◽  
Caspase 3 ◽  
Tunel Assay ◽  
Methylprednisolone Acetate ◽  
Drg Neurons ◽  
Isolated Rat

Background: Epidural and intrathecal injections of methylprednisolone acetate (MPA) have become the most commonly performed interventional procedures in the United States and worldwide in the last 2 decades. However neuraxial MPA injection has been dogged by controversy regarding the presence of different additives used in commercially prepared glucocorticoids. We previously showed that MPA could be rendered 85% free of polyethylene glycol (PEG) by a simple physical separation of elements in the suspension. Objective: The objective of the present study was to explore a possible cytotoxic effect of commercially available MPA (with intact or reduced preservatives) on rat sensory neurons. Methods: We exposed primary dissociated rat dorsal root ganglia (DRG) sensory neurons to commercially available MPA for 24 hours with either the standard (commercial) concentration of preservatives or to different fractions following separation (MPA suspension whose preservative concentration had been reduced, or fractions containing higher concentrations of preservatives). Cells were stained with the TUNEL assay kit to detect apoptotic cells and images were taken on the Bio-Rad Laser Sharp-2000 system. We also detected expression of caspase-3, as an indicator of apoptosis in cell lysates. Results: We exposed sensory neurons from rat DRG to different concentrations of MPA from the original commercially prepared vial. TUNEL assay showed dose-related responses and increased percentages of apoptotic cells with increasing concentrations of MPA. Increased concentrations of MPA caused 1.5 – 2 times higher caspase-3 expression in DRG sensory neurons than in control cells (ANOVA, P = 0.001). Our results showed that MPA with reduced preservatives caused significantly less apoptosis observed with TUNEL assay labeling (P < 0.001) and caspase-3 immunoblotting (P ≤ 0.001) than in neurons exposed to MPA from a commercially prepared vial or “clear phase” that contained higher concentrations of preservatives. Even though MPA with reduced preservatives caused 12.5% more apoptosis in DRG sensory neurons than in control cells, post hoc analysis showed no differences between these 2 groups. Limitations: Our data was collected from in vitro isolated rat DRG neurons. There is a possibility that in vivo neurons have different extents of vulnerability compared to isolated neurons. Conclusions: Results of the present study identified a cytotoxic effect of commercially available MPA with preservatives or with a “clear phase” containing higher concentrations of preservatives on primary isolated rat DRG sensory neurons. This was shown by TUNEL positive assay and by increased caspase-3 expression as one of the final executing steps in apoptotic pathways in DRG neurons. However, our results showed no statistically significant difference between the control cells (salinetreated) and cells treated with MPA with reduced concentrations of preservatives, pointing out that either PEG or myristylgamma-picolinium chloride (MGPC) or their combination have harmful effects on these cells. Reduction of concentrations of preservatives from commercially available MPA suspensions by using the simple method of inverting vials for 2 hours could be considered useful in clinical practice to enhance the safety of this depot steroid when injected neuraxially. Key words: Methylprednisolone acetate, preservatives, dorsal root ganglion sensory neurons, cytotoxic effect, polyethylene glycol, myristylgamma-picolinium chloride

scholarly journals Comparison of histological changes of sensory neurons of Dorsal Root Ganglion of spinal nerve in different age groups in rabbits

2015 ◽  
Vol 39 (2) ◽  
pp. 42-46
Author(s):  
Ali Ghanim Al-Okaili
Keyword(s):  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Light Microscope ◽  
Dorsal Root ◽  
Age Factors ◽  
Age Groups ◽  
Spinal Nerve ◽  
Histological Changes ◽  
Made In

     The aim of the study is to compare the histological changes that occur in the sensory neurons of dorsal root ganglion at L6 and L7 levels of the spinal nerve in different age groups in rabbits. Fifteen rabbits were divided into three groups of equal number according to their age (weaning, maturation and adult). Dorsal root ganglion of spinal nerve at L6 and L7 levels were removed and examined histologically under light microscope. Comparison were made in diameters of neurons and their numbers in different age. The results showed a significant (P<0.05) decrease in the number of sensory neurons and a significant (P<0.05) increase in their diameters with advancing age. In conclusion, the structures of sensory neurons are altering by the age factors in which morphology, number, and color of neurons change also.

Dorsal root ganglion stimulation lead fractures: potential mechanisms and ways to avoid

2021 ◽  
Vol 14 (5) ◽  
pp. e241353
Author(s):  
Gaurav Chauhan ◽  
Brandon I Roth ◽  
Nagy Mekhail
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Case Report ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Unusual Case ◽  
Pain Syndrome ◽  
Structural Instability ◽  
Probable Mechanism ◽  
Lead Fracture

Dorsal root ganglion stimulation (DRGS) therapy is a rapidly emerging tool being used by pain physicians in the treatment of chronic pain. Complex regional pain syndrome (CRPS), a debilitating disease whose mechanism is still has yet to be fully elucidated, is a common pathology targeted by DRGS therapy, often better results than traditional spinal cord stimulation. DRGS therapy, however, is not bereft of complications. Lead migration and fracture are two examples in particular that are among the most common of these complications. The authors report an unusual case of lost efficacy due to lead fractures in patients with CRPS treated with DRGS. The case report narrates identification, management and probable mechanism of DRGS lead fracture. The structural instability of DRGS leads can yield distressing symptoms at any point during the therapy, and physicians should be cognisant of the complications of DRGS therapy.

Delta/Notch signaling promotes formation of zebrafish neural crest by repressing Neurogenin 1 function

Development ◽  
2002 ◽  
Vol 129 (11) ◽  
pp. 2639-2648 ◽  
Author(s):  
Robert A. Cornell ◽  
Judith S. Eisen
Keyword(s):  
Dorsal Root Ganglion ◽  
Neural Crest ◽  
Notch Signaling ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Cell Formation ◽  
Dorsal Root Ganglion Neurons ◽  
Primary Neurons ◽  
Different Types ◽  
Ganglion Neurons

In zebrafish, cells at the lateral edge of the neural plate become Rohon-Beard primary sensory neurons or neural crest. Delta/Notch signaling is required for neural crest formation. ngn1 is expressed in primary neurons; inhibiting Ngn1 activity prevents Rohon-Beard cell formation but not formation of other primary neurons. Reducing Ngn1 activity in embryos lacking Delta/Notch signaling restores neural crest formation, indicating Delta/Notch signaling inhibits neurogenesis without actively promoting neural crest. Ngn1 activity is also required for later development of dorsal root ganglion sensory neurons; however, Rohon-Beard neurons and dorsal root ganglion neurons are not necessarily derived from the same precursor cell. We propose that temporally distinct episodes of Ngn1 activity in the same precursor population specify these two different types of sensory neurons.

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