scholarly journals An integrative approach to the facile functional classification of dorsal root ganglion neuronal subclasses

2020 ◽  
Vol 117 (10) ◽  
pp. 5494-5501 ◽  
Author(s):  
Mario J. Giacobassi ◽  
Lee S. Leavitt ◽  
Shrinivasan Raghuraman ◽  
Rishi Alluri ◽  
Kevin Chase ◽  
...  

Somatosensory neurons have historically been classified by a variety of approaches, including structural, anatomical, and genetic markers; electrophysiological properties; pharmacological sensitivities; and more recently, transcriptional profile differentiation. These methodologies, used separately, have yielded inconsistent classification schemes. Here, we describe phenotypic differences in response to pharmacological agents as measured by changes in cytosolic calcium concentration for the rapid classification of neurons in vitro; further analysis with genetic markers, whole-cell recordings, and single-cell transcriptomics validated these findings in a functional context. Using this general approach, which we refer to as tripartite constellation analysis (TCA), we focused on large-diameter dorsal-root ganglion (L-DRG) neurons with myelinated axons. Divergent responses to the K-channel antagonist, κM-conopeptide RIIIJ (RIIIJ), reliably identified six discrete functional cell classes. In two neuronal subclasses (L1 and L2), block with RIIIJ led to an increase in [Ca]i. Simultaneous electrophysiology and calcium imaging showed that the RIIIJ-elicited increase in [Ca]i corresponded to different patterns of action potentials (APs), a train of APs in L1 neurons, and sporadic firing in L2 neurons. Genetically labeled mice established that L1 neurons are proprioceptors. The single-cell transcriptomes of L1 and L2 neurons showed that L2 neurons are Aδ–low-threshold mechanoreceptors. RIIIJ effects were replicated by application of the Kv1.1 selective antagonist, Dendrotoxin-K, in several L-DRG subclasses (L1, L2, L3, and L5), suggesting the presence of functional Kv1.1/Kv1.2 heteromeric channels. Using this approach on other neuronal subclasses should ultimately accelerate the comprehensive classification and characterization of individual somatosensory neuronal subclasses within a mixed population.

Author(s):  
Edward C. Emery ◽  
Patrik Ernfors

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.


Glia ◽  
2003 ◽  
Vol 45 (1) ◽  
pp. 54-58 ◽  
Author(s):  
Jewel L. Podratz ◽  
Esther H. Rodriguez ◽  
Anthony J. Windebank

2020 ◽  
Author(s):  
Jianjun Zhu ◽  
Keyue Xie ◽  
Songlei Liu ◽  
Qiuli He ◽  
Ge Luo ◽  
...  

Abstract Background: At present, different views have been proposed on the radiofrequency treatment modes and parameters of radiofrequency thermocoagulation of the spinal dorsal root ganglion for the treatment of postherpetic neuralgia. It is urgent to identify a novel and more effective radiofrequency therapy for patients with postherpetic neuralgia. Methods: A total of 60 patients who underwent radiofrequency thermocoagulation therapy for postherpetic neuralgia in the pain department of our Hospital were retrospectively reviewed from January 2013 to November 2017. According to the different surgical methods, the patients were divided into the following groups: unipolar group (CRF) and bipolar group (DCRF). Subsequently, the pain scores (NRS) were evaluated at the following specific time points: before the operation, on the 1st day after the operation, in 3 and 6 months after the operation and in 1 and 2 years after the operation. Moreover, the incidence of intraoperative and postoperative complications and the degree of pain relief were evaluated in order to assess the efficacy and prognosis of radiofrequency thermocoagulation in the two groups. The in vitro ovalbumin experiment was used to indicate the effects of unipolar and bipolar radiofrequency thermocoagulation.Results: In this study, the intra-group comparison indicated that compared with the preoperative NRS, the postoperative NRS decreased significantly; the inter-group comparison demonstrated that the NRS of the DCRF group was lower than that of the CRF group at all time points from 6 months to 2 years following the operation. The total effective rate of the DCRF group was significantly higher than that of the CRF group in 2 years following the operation. The incidence of numbness in the DCRF group was higher than that noted in the CRF group at each time point following the operation. The ovalbumin experiments in vitro indicated that the effects of radiofrequency thermocoagulation were optimal when the distance between the two needles was 5 mm.Conclusion: Bipolar spinal root ganglion radiofrequency thermocoagulation exhibits a longer duration and higher effective rate in the treatment of postherpetic neuralgia and it’s a treatment method worth promoting.


2012 ◽  
Vol 49 (4) ◽  
pp. 464-474 ◽  
Author(s):  
Steven J. Jacques ◽  
Zubair Ahmed ◽  
Anna Forbes ◽  
Michael R. Douglas ◽  
Vasanthy Vigenswara ◽  
...  

1989 ◽  
Vol 62 (3) ◽  
pp. 657-664 ◽  
Author(s):  
K. Morita ◽  
Y. Katayama

1. Intracellular recordings were made from bullfrog dorsal root ganglion (DRG) neurons in vitro. They were divided into three types, As, Ar, and C, according to their conduction velocity and their sensitivity to tetrodotoxin [TTX (less than or equal to 1 microM)]; an As neuron had a fast conduction velocity (13-50 m/s, mean = 31 m/s, n = 73) and TTX-sensitive sodium soma spikes: an Ar neuron showed a fast conduction velocity (4-28 m/s, mean = 14 m/s, n = 52) and TTX-resistant sodium soma spikes; and a C neuron had a slow conduction velocity (0.16-0.8 m/s, mean = 0.4 m/s, n = 49) and TTX-resistant sodium-calcium soma spikes. 2. Superfusion of acetylcholine [ACh (0.3 microM-1 mM)] produced a fast depolarization in 70% of Ar and in 50% of C neurons. No As neuron showed a fast depolarization in response to ACh. The ACh-induced fast response persisted in calcium-free or TTX-containing solutions. 3. The response in both Ar and C neurons was similar except in time course; the response was always more rapid in C than in Ar neurons. The response was always associated with a decreased membrane resistance and reversed in polarity at about -30 mV. The reversal potential varied with both sodium and potassium concentrations of the superfusing solutions. 4. Nicotine, (+)-tubocurarine [(+)-TC], and hexamethonium reversibly blocked the ACh fast response.(ABSTRACT TRUNCATED AT 250 WORDS)


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