scholarly journals Spike propagation through the dorsal root ganglia in an unmyelinated sensory neuron: a modeling study

2015 ◽  
Vol 114 (6) ◽  
pp. 3140-3153 ◽  
Author(s):  
Danielle Sundt ◽  
Nikita Gamper ◽  
David B. Jaffe
Keyword(s):  
Ion Channels ◽  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Major Type ◽  
Delayed Rectifier ◽  
Kcnq Channels ◽  
Voltage Gated ◽  
C Fibers ◽  
M Channels

Unmyelinated C-fibers are a major type of sensory neurons conveying pain information. Action potential conduction is regulated by the bifurcation (T-junction) of sensory neuron axons within the dorsal root ganglia (DRG). Understanding how C-fiber signaling is influenced by the morphology of the T-junction and the local expression of ion channels is important for understanding pain signaling. In this study we used biophysical computer modeling to investigate the influence of axon morphology within the DRG and various membrane conductances on the reliability of spike propagation. As expected, calculated input impedance and the amplitude of propagating action potentials were both lowest at the T-junction. Propagation reliability for single spikes was highly sensitive to the diameter of the stem axon and the density of voltage-gated Na+ channels. A model containing only fast voltage-gated Na+ and delayed-rectifier K+ channels conducted trains of spikes up to frequencies of 110 Hz. The addition of slowly activating KCNQ channels (i.e., KV7 or M-channels) to the model reduced the following frequency to 30 Hz. Hyperpolarization produced by addition of a much slower conductance, such as a Ca2+-dependent K+ current, was needed to reduce the following frequency to 6 Hz. Attenuation of driving force due to ion accumulation or hyperpolarization produced by a Na+-K+ pump had no effect on following frequency but could influence the reliability of spike propagation mutually with the voltage shift generated by a Ca2+-dependent K+ current. These simulations suggest how specific ion channels within the DRG may contribute toward therapeutic treatments for chronic pain.

scholarly journals P2X2 receptors differentiate placodal vs. neural crest C-fiber phenotypes innervating guinea pig lungs and esophagus

2008 ◽  
Vol 295 (5) ◽  
pp. L858-L865 ◽  
Author(s):  
Kevin Kwong ◽  
Marian Kollarik ◽  
Christina Nassenstein ◽  
Fei Ru ◽  
Bradley J. Undem
Keyword(s):  
Guinea Pig ◽  
Neural Crest ◽  
Single Cell ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Receptor Activation ◽  
Rt Pcr ◽  
C Fibers ◽  
Embryonic Origin ◽  
Ganglion Neurons

The lungs and esophagus are innervated by sensory neurons with somata in the nodose, jugular, and dorsal root ganglion. These sensory ganglia are derived from embryonic placode (nodose) and neural crest tissues (jugular and dorsal root ganglia; DRG). We addressed the hypothesis that the neuron's embryonic origin (e.g., placode vs. neural crest) plays a greater role in determining particular aspects of its phenotype than the environment in which it innervates (e.g., lungs vs. esophagus). This hypothesis was tested using a combination of extracellular and patch-clamp electrophysiology and single-cell RT-PCR from guinea pig neurons. Nodose, but not jugular C-fibers innervating the lungs and esophagus, responded to α,β-methylene ATP with action potential discharge that was sensitive to the P2X3 (P2X2/3) selective receptor antagonist A-317491. The somata of lung- and esophagus-specific sensory fibers were identified using retrograde tracing with a fluorescent dye. Esophageal- and lung-traced neurons from placodal tissue (nodose neurons) responded similarly to α,β-methylene ATP (30 μM) with a large sustained inward current, whereas in neurons derived from neural crest tissue (jugular and DRG neurons), the same dose of α,β-methylene ATP resulted in only a transient rapidly inactivating current or no detectable current. It has been shown previously that only activation of P2X2/3 heteromeric receptors produce sustained currents, whereas homomeric P2X3 receptor activation produces a rapidly inactivating current. Consistent with this, single-cell RT-PCR analysis revealed that the nodose ganglion neurons innervating the lungs and esophagus expressed mRNA for P2X2 and P2X3 subunits, whereas the vast majority of jugular and dorsal root ganglia innervating these tissues expressed only P2X3 mRNA with little to no P2X2 mRNA expression. We conclude that the responsiveness of C-fibers innervating the lungs and esophagus to ATP and other purinergic agonists is determined more by their embryonic origin than by the environment of the tissue they ultimately innervate.

Suppression of KCNQ/M Potassium Channel in Dorsal Root Ganglia Neurons Contributes to the Development of Osteoarthritic Pain

Pharmacology ◽  
2019 ◽  
Vol 103 (5-6) ◽  
pp. 257-262 ◽  
Author(s):  
Fan Zhang ◽  
Yani Liu ◽  
Dandan Zhang ◽  
Xizhenzi Fan ◽  
Decheng Shao ◽  
...  
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Strong Impact ◽  
Drg Neurons ◽  
M Current ◽  
Mechanical Threshold ◽  
Dorsal Root Ganglia Neurons ◽  
M Channels ◽  
Osteoarthritic Pain

Osteoarthritic pain has a strong impact on patients’ quality of life. Understanding the pathogenic mechanisms underlying osteoarthritic pain will likely lead to the development of more effective treatments. In the present study of osteoarthritic model rats, we observed a reduction of M-current density and a remarkable decrease in the levels of KCNQ2 and KCNQ3 proteins and mRNAs in dorsal root ganglia (DRG) neurons, which were associated with hyperalgesic behaviors. The activation of KCNQ/M channels with flupirtine significantly increased the mechanical threshold and prolonged the withdrawal latency of osteoarthritic model rats at 3–14 days after model induction, and all effects of flupirtine were blocked by KCNQ/M-channel antagonist, XE-991. Together, these results indicate that suppression of KCNQ/M channels in primary DRG neurons plays a crucial role in the development of osteoarthritic pain.

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

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.

scholarly journals Identification of genes regulating sensory neuron genesis and differentiation in the avian dorsal root ganglia

2004 ◽  
Vol 229 (3) ◽  
pp. 618-629 ◽  
Author(s):  
Branden R. Nelson ◽  
Meru Sadhu ◽  
Jennifer C. Kasemeier ◽  
Lawrence W. Anderson ◽  
Frances Lefcort
Keyword(s):  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root

scholarly journals Functional Analysis of a Voltage-Gated Sodium Channel and Its Splice Variant from Rat Dorsal Root Ganglia

2002 ◽  
Vol 70 (6) ◽  
pp. 2262-2272 ◽  
Author(s):  
Paul S. Dietrich ◽  
Joseph G. McGivern ◽  
Stephen G. Delgado ◽  
Bruce D. Koch ◽  
Richard M. Eglen ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Sodium Channel ◽  
Dorsal Root Ganglia ◽  
Splice Variant ◽  
Dorsal Root ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

scholarly journals Cannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity

2021 ◽  
Vol 2 ◽  
Author(s):  
Zachary K. Ford ◽  
Ashlie N. Reker ◽  
Sisi Chen ◽  
Feni Kadakia ◽  
Alexander Bunk ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Cannabinoid Receptors ◽  
Calcium Influx ◽  
Membrane Properties ◽  
Neuron Activity ◽  
Membrane Excitability ◽  
Bidirectional Modulation

Cannabinoid receptors have been identified as potential targets for analgesia from studies on animal physiology and behavior, and from human clinical trials. Here, we sought to improve translational understanding of the mechanisms of cannabinoid-mediated peripheral analgesia. Human lumbar dorsal root ganglia were rapidly recovered from organ donors to perform physiological and anatomical investigations into the potential for cannabinoids to mediate analgesia at the level of the peripheral nervous system. Anatomical characterization of in situ gene expression and immunoreactivity showed that 61 and 53% of human sensory neurons express the CB1 gene and receptor, respectively. Calcium influx evoked by the algogen capsaicin was measured by Fura-2AM in dissociated human sensory neurons pre-exposed to the inflammatory mediator prostaglandin E2 (PGE2) alone or together with CB13 (1 μM), a cannabinoid agonist with limited blood–brain barrier permeability. Both a higher proportion of neurons and a greater magnitude of response to capsaicin were observed after exposure to CB13, indicating cannabinoid-mediated sensitization. In contrast, membrane properties measured by patch-clamp electrophysiology demonstrated that CB13 suppressed excitability and reduced action potential discharge in PGE2-pre-incubated sensory neurons, suggesting the suppression of sensitization. This bidirectional modulation of sensory neuron activity suggests that cannabinoids may suppress overall membrane excitability while simultaneously enhancing responsivity to TRPV1-mediated stimuli. We conclude that peripherally restricted cannabinoids may have both pro- and anti-nociceptive effects in human sensory neurons.

scholarly journals Expression of huntingtin-associated protein 1 in adult mouse dorsal root ganglia and its neurochemical characterization in reference to sensory neuron subpopulations

IBRO Reports ◽  
2020 ◽  
Vol 9 ◽  
pp. 258-269 ◽  
Author(s):  
Md Nabiul Islam ◽  
Naoki Maeda ◽  
Emi Miyasato ◽  
Mir Rubayet Jahan ◽  
Abu Md Mamun Tarif ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Adult Mouse
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