Molecular, Cellular and Circuit Basis of Cholinergic Modulation of Pain

Naser, Paul Vincent; Kuner, Rohini

doi:10.1016/j.neuroscience.2017.08.049

Cited by 100 publications

(78 citation statements)

References 124 publications

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“…Nicotinic receptors are prominently expressed in DRG neurons and are known to play a role in sensory neuron excitability [33]. We focused on several subunits, alpha 6, 9 and 10, that show prominent species differences in DRG mRNA expression or specificity based on RNA sequencing experiments [37].…”

Section: Nicotinic Acetylcholine Receptorsmentioning

confidence: 99%

Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscopein situhybridization

Shiers

Klein

Price

2020

Preprint

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Next generation transcriptomics in combination with imaging-based approaches have emerged as powerful tools for the characterization of dorsal root ganglion (DRG) neuronal subpopulations. The mouse DRG has been wellcharacterized by many independently conducted studies with convergent findings, but few studies have directly compared expression of population markers between mouse and human. This is important because of our increasing reliance on the mouse as a preclinical model for translational studies. While calcitonin gene-related peptide (CGRP) and P2X purinergic ion channel type 3 receptor (P2X3R) have been used to define peptidergic and non-peptidergic nociceptor subpopulations, respectively, in mouse DRG, these populations may be different in other species. To directly test this, as well as a host of other markers, we used multiplex RNAscope in-situ hybridization to elucidate the distribution of a multitude of unique and classic neuronal mRNAs in peptidergic (CGRP expressing) and non-peptidergic (P2X3R expressing) nociceptor subpopulations in mouse and human DRG. We found a large overlapping CGRP and P2X3R neuronal subpopulation in human, lumbar DRG that was not present in mouse. We also found differential expression in a variety of mRNAs for Trp-channels, cholinergic receptors, potassium channels, sodium channels, other markers/targets. These data offer insights into the spatial and functional organization of neuronal cell subpopulations in the rodent and human DRG and support the idea that sensory system organizational principles are likely different between both species.

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Section: Nicotinic Acetylcholine Receptorsmentioning

confidence: 99%

Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscopein situhybridization

Shiers

Klein

Price

2020

Preprint

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“…Interestingly, two members of the muscarinic acetylcholine receptor family, Chrm4 (+2.1 log2FC) and Chrm5 (+2.1 log2FC), were also significantly enriched. As cholinergic signaling is well-known to contribute to pain modulation in the spinal cord, these two receptors may play particular roles in SST neurons gating mechanical pain (Naser and Kuner, 2017).…”

Section: G-protein Coupled Receptorsmentioning

confidence: 99%

Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn

Chamessian

Young

Qadri

et al. 2017

Preprint

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The spinal dorsal horn (SDH) is comprised of distinct neuronal populations that process different . CC-BY-NC-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/215657 doi: bioRxiv preprint first posted online Nov. 8, 2017; and Gpr26). Taken together, our study unveils a comprehensive transcriptional signature for SST neurons, highlights promising candidate genes for future analgesic development, and establishes a flexible method for transcriptional profiling of any spinal cord cell type.

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“…For instance, there is a large body of evidence pointing to the importance of muscarinic signaling in pain control at the level of the spinal dorsal horns. In particular, ACh receptors profoundly regulate nociceptive transmission in the spinal cord via pre-and postsynaptic mechanisms and the direct activation of mAChRs reduces pain in rodents and humans, while their inhibition induces hypersensitivity (for review see Naser and Kuner, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Besides its modulatory quality, acetylcholine (ACh) also acts as one of the most prominent neurotransmitters in the peripheral and central nervous system. Interestingly, cholinergic transmission profoundly affects the perception of pain via both nicotinic (nAChRs) and muscarinic (mAChRs) receptors (for review see Naser and Kuner, 2017). There is considerable direct and indirect evidence that ACh is widely distributed in the region of NTS (Kobayashi et al, 1978;Criscione et al, 1983;Ernsberger et al, 1988;Ruggiero et al, 1990;Zoccal et al, 2014) where both mAChRs and nAChRs are present.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory modulation of the cough reflex by acetylcholine in the caudal nucleus tractus solitarii of the rabbit

Cinelli

Iovino

Bongianni

et al. 2018

Respiratory Physiology & Neurobiology

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A cholinergic system has been described in the nucleus tractus solitarii (NTS). However, no information is available on the role played by acetylcholine (ACh) in the modulation of the cough reflex within the caudal NTS that has an important function in cough regulation. We addressed this issue making use of bilateral microinjections (30-50 nl) of 10 mM ACh combined with 5 mM physostigmine as well as of 10 mM mecamylamine or 10 mM scopolamine into the caudal NTS of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Microinjections of ACh/physostigmine caused depressant effects on the cough reflex induced by mechanical and chemical stimulation of the tracheobronchial tree. They also elicited transient increases in respiratory frequency and decreases in abdominal activity. These effects were prevented by scopolamine, but not by mecamylamine. The results show for the first time that ACh exerts an inhibitory modulation of the cough reflex through muscarinic receptors within the caudal NTS. They also may provide hints for novel antitussive approaches.

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Molecular, Cellular and Circuit Basis of Cholinergic Modulation of Pain

Cited by 100 publications

References 124 publications

Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscopein situhybridization

Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscopein situhybridization

Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn

Inhibitory modulation of the cough reflex by acetylcholine in the caudal nucleus tractus solitarii of the rabbit

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