The 5-HT2A receptor is mainly expressed in nociceptive sensory neurons in rat lumbar dorsal root ganglia

Multiple muscarinic receptor subtypes are present on sensory neurons that may be involved in the modulation of nociception. In this study we focused on the presence of the muscarinic receptor subtypes, M2 and M3 (M2R, M3R), in adult rat lumbar dorsal root ganglia (DRG) at the functional ([Ca2+]i measurement), transcriptional (RT-PCR), and translational level (immunohistochemistry). After 1 day in culture exposure of dissociated medium-sized neurons (20–35 μm diam) to muscarine was followed by rises in [Ca2+]i in 76% of the neurons. The [Ca2+]i increase was absent after removal of extracellular calcium and did not desensitize after repetitive application of the agonist. This rise in [Ca2+]i may be explained by the expression of M3R, which can induce release of calcium from internal stores via inositoltrisphospate. Indeed the effect was antagonized by the muscarinic receptor antagonist atropine as well as by the M3R antagonist, 4-diphenylacetoxy-N-(2 chloroethyl)-piperidine hydrochloride (4-DAMP). The pharmacological identification of M3R was corroborated by RT-PCR of total RNA and single-cell RT-PCR, which revealed the presence of mRNA for M3R in lumbar DRG and in single sensory neurons. In addition, RT-PCR also revealed the expression of M2R, which did not seem to contribute to the calcium changes since it was not prevented by the M2 receptor antagonist, gallamine. Immunohistochemistry demonstrated the presence of M2R and M3R in medium-sized lumbar DRG neurons that also coexpressed binding sites for the lectin I-B4, a marker for mainly cutaneous nociceptors. The occurrence of muscarinic receptors in putative nociceptive I-B4-positive neurons suggests the involvement of these acetylcholine receptors in the modulation of processing of nociceptive stimuli.

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Frataxin gene editing rescues Friedreich’s ataxia pathology in dorsal root ganglia organoid-derived sensory neurons

Nature Communications ◽

10.1038/s41467-020-17954-3 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Pietro Giuseppe Mazzara ◽

Sharon Muggeo ◽

Mirko Luoni ◽

Luca Massimino ◽

Mattia Zaghi ◽

...

Keyword(s):

Sensory Neurons ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Gene Editing ◽

Friedreich’S Ataxia ◽

Friedreich's Ataxia ◽

Frataxin Gene

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RNA-Binding Proteins HuB, HuC, and HuD are Distinctly Regulated in Dorsal Root Ganglia Neurons from STZ-Sensitive Compared to STZ-Resistant Diabetic Mice

International Journal of Molecular Sciences ◽

10.3390/ijms20081965 ◽

2019 ◽

Vol 20 (8) ◽

pp. 1965 ◽

Cited By ~ 1

Author(s):

Cosmin Cătălin Mustăciosu ◽

Adela Banciu ◽

Călin Mircea Rusu ◽

Daniel Dumitru Banciu ◽

Diana Savu ◽

...

Keyword(s):

Gene Expression ◽

Body Weight ◽

Sensory Neurons ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Transcriptional Control ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Diabetic Mice

The neuron-specific Elav-like Hu RNA-binding proteins were described to play an important role in neuronal differentiation and plasticity by ensuring the post-transcriptional control of RNAs encoding for various proteins. Although Elav-like Hu proteins alterations were reported in diabetes or neuropathy, little is known about the regulation of neuron-specific Elav-like Hu RNA-binding proteins in sensory neurons of dorsal root ganglia (DRG) due to the diabetic condition. The goal of our study was to analyze the gene and protein expression of HuB, HuC, and HuD in DRG sensory neurons in diabetes. The diabetic condition was induced in CD-1 adult male mice with single-intraperitoneal injection of streptozotocin (STZ, 150 mg/kg), and 8-weeks (advanced diabetes) after induction was quantified the Elav-like proteins expression. Based on the glycemia values, we identified two types of responses to STZ, and mice were classified in STZ-resistant (diabetic resistant, glycemia < 260 mg/dL) and STZ-sensitive (diabetic, glycemia > 260 mg/dL). Body weight measurements indicated that 8-weeks after STZ-induction of diabetes, control mice have a higher increase in body weight compared to the diabetic and diabetic resistant mice. Moreover, after 8-weeks, diabetic mice (19.52 ± 3.52 s) have longer paw withdrawal latencies in the hot-plate test than diabetic resistant (11.36 ± 1.92 s) and control (11.03 ± 1.97 s) mice, that correlates with the installation of warm hypoalgesia due to the diabetic condition. Further on, we evidenced the decrease of Elav-like gene expression in DRG neurons of diabetic mice (Elavl2, 0.68 ± 0.05 fold; Elavl3, 0.65 ± 0.01 fold; Elavl4, 0.53 ± 0.07 fold) and diabetic resistant mice (Ealvl2, 0.56 ± 0.07 fold; Elavl3, 0.32 ± 0.09 fold) compared to control mice. Interestingly, Elav-like genes have a more accentuated downregulation in diabetic resistant than in diabetic mice, although hypoalgesia was evidenced only in diabetic mice. The Elav-like gene expression changes do not always correlate with the Hu protein expression changes. To detail, HuB is upregulated and HuD is downregulated in diabetic mice, while HuB, HuC, and HuD are downregulated in diabetic resistant mice compared to control mice. To resume, we demonstrated HuD downregulation and HuB upregulation in DRG sensory neurons induced by diabetes, which might be correlated with altered post-transcriptional control of RNAs involved in the regulation of thermal hypoalgesia condition caused by the advanced diabetic neuropathy.

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Neuronal intermediate filament expression in rat dorsal root ganglia sensory neurons: An in vivo and in vitro study

Neuroscience ◽

10.1016/j.neuroscience.2008.02.080 ◽

2008 ◽

Vol 153 (4) ◽

pp. 1153-1163 ◽

Cited By ~ 42

Author(s):

M. Fornaro ◽

J.M. Lee ◽

S. Raimondo ◽

S. Nicolino ◽

S. Geuna ◽

...

Keyword(s):

Sensory Neurons ◽

Dorsal Root Ganglia ◽

Intermediate Filament ◽

Dorsal Root ◽

In Vitro Study ◽

Vitro Study

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Isolation and Culture of Sensory Neurons From the Dorsal-Root Ganglia of Embryonic or Adult Rats

Pain Research - Methods in Molecular Medicine ◽

10.1385/1-59259-770-x:055 ◽

2004 ◽

pp. 189-202 ◽

Cited By ~ 8

Author(s):

Thomas H. Burkey ◽

Cynthia M. Hingtgen ◽

Michael R. Vasko

Keyword(s):

Sensory Neurons ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Adult Rats

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An Evaluation of a Method for the Detection of Sensory Ganglia in Product Derived from Advanced Meat Recovery Systems†

Journal of Food Protection ◽

10.4315/0362-028x-71.11.2307 ◽

2008 ◽

Vol 71 (11) ◽

pp. 2307-2311 ◽

Cited By ~ 1

Author(s):

SCOTT HAFNER ◽

MARY T. SUTTON ◽

JOSEPH HILL ◽

PATRICK C. McCASKEY ◽

LYNDA COLLINS KELLEY

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Single Cell ◽

Sensory Neurons ◽

Dorsal Root Ganglia ◽

Satellite Cells ◽

Dorsal Root ◽

Immunohistochemical Staining ◽

Staining Pattern ◽

Acidic Protein ◽

Sensory Ganglia

A method is described for the identification of dorsal root ganglia (DRG)–associated sensory neurons within advanced meat recovery (AMR) product derived from bovine vertebral columns. This method relies on the unique microanatomy of sensory neurons and immunohistochemical staining, primarily for glial fibrillary acidic protein. Sensory neurons are variably sized unipolar neurons, exhibiting a single-cell process that is rarely seen in histologic sections. These neurons are surrounded by a prominent ring of glial fibrillary acidic protein–positive satellite cells that produce a distinctive and readily identifiable staining pattern in histologic sections. Fragmented DRG were detected to the 0.25% level in samples of ground beef or nonvertebral-origin AMR product spiked with these sensory ganglia. Similarly examined commercially produced nonvertebral-origin AMR product (n = 157) did not contain sensory ganglia, while 3.3% of vertebral-origin AMR product (n = 364) contained fragmented DRG.

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Epigenomic signatures underpin the axonal regenerative ability of dorsal root ganglia sensory neurons

Nature Neuroscience ◽

10.1038/s41593-019-0490-4 ◽

2019 ◽

Vol 22 (11) ◽

pp. 1913-1924 ◽

Cited By ~ 18

Author(s):

Ilaria Palmisano ◽

Matt C. Danzi ◽

Thomas H. Hutson ◽

Luming Zhou ◽

Eilidh McLachlan ◽

...

Keyword(s):

Sensory Neurons ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Regenerative Ability

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Enhanced T-type calcium channel 3.2 activity in sensory neurons contributes to neuropathic-like pain of monosodium iodoacetate-induced knee osteoarthritis

Molecular Pain ◽

10.1177/1744806920963807 ◽

2020 ◽

Vol 16 ◽

pp. 174480692096380

Author(s):

Seung Min Shin ◽

Yongsong Cai ◽

Brandon Itson-Zoske ◽

Chensheng Qiu ◽

Xu Hao ◽

...

Keyword(s):

Sensory Neuron ◽

Sensory Neurons ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Spinal Dorsal Horn ◽

Primary Sensory Neurons ◽

Primary Sensory Neuron ◽

Spinal Dorsal ◽

Osteoarthritis Pain ◽

Monosodium Iodoacetate

The monosodium iodoacetate knee osteoarthritis model has been widely used for the evaluation of osteoarthritis pain, but the pathogenesis of associated chronic pain is not fully understood. The T-type calcium channel 3.2 (CaV3.2) is abundantly expressed in the primary sensory neurons, in which it regulates neuronal excitability at both the somata and peripheral terminals and facilitates spontaneous neurotransmitter release at the spinal terminals. In this study, we investigated the involvement of primary sensory neuron-CaV3.2 activation in monosodium iodoacetate osteoarthritis pain. Knee joint osteoarthritis pain was induced by intra-articular injection of monosodium iodoacetate (2 mg) in rats, and sensory behavior was evaluated for 35 days. At that time, knee joint structural histology, primary sensory neuron injury, and inflammatory gliosis in lumbar dorsal root ganglia, and spinal dorsal horn were examined. Primary sensory neuron-T-type calcium channel current by patch-clamp recording and CaV3.2 expression by immunohistochemistry and immunoblots were determined. In a subset of animals, pain relief by CaV3.2 inhibition after delivery of CaV3.2 inhibitor TTA-P2 into sciatic nerve was investigated. Knee injection of monosodium iodoacetate resulted in osteoarthritis histopathology, weight-bearing asymmetry, sensory hypersensitivity of the ipsilateral hindpaw, and inflammatory gliosis in the ipsilateral dorsal root ganglia, sciatic nerve, and spinal dorsal horn. Neuronal injury marker ATF-3 was extensively upregulated in primary sensory neurons, suggesting that neuronal damage was beyond merely knee-innervating primary sensory neurons. T-type current in dissociated primary sensory neurons from lumbar dorsal root ganglia of monosodium iodoacetate rats was significantly increased, and CaV3.2 protein levels in the dorsal root ganglia and spinal dorsal horn ipsilateral to monosodium iodoacetate by immunoblots were significantly increased, compared to controls. Perineural application of TTA-P2 into the ipsilateral sciatic nerve alleviated mechanical hypersensitivity and weight-bearing asymmetry in monosodium iodoacetate osteoarthritis rats. Overall, our findings demonstrate an elevated CaV3.2 expression and enhanced function of primary sensory neuron-T channels in the monosodium iodoacetate osteoarthritis pain. Further study is needed to delineate the importance of dysfunctional primary sensory neuron-CaV3.2 in osteoarthritis pain.

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