Localized and non-contact mechanical stimulation of dorsal root ganglion sensory neurons using scanning ion conductance microscopy

2007 ◽  
Vol 159 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Daniel Sánchez ◽  
Uma Anand ◽  
Julia Gorelik ◽  
Christopher D. Benham ◽  
Chas Bountra ◽  
...  
Pain ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Dongman Chao ◽  
Christina M. Mecca ◽  
Guoliang Yu ◽  
Ian Segel ◽  
Michael S. Gold ◽  
...  

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.


Author(s):  
Kentaro Nishida ◽  
Yuka Nomura ◽  
Kanako Kawamori ◽  
Akihiro Ohishi ◽  
Kazuki Nagasawa

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.


1986 ◽  
Vol 55 (4) ◽  
pp. 635-643 ◽  
Author(s):  
P. Grigg ◽  
H. G. Schaible ◽  
R. F. Schmidt

Recordings were performed from sciatic nerve or dorsal root filaments in 28 cats to study single group III (conduction velocity 2.5-20 m/s) and group IV (conduction velocity less than 2.5 m/s) units supplying the knee joint via the posterior articular nerve (PAN). In seven of these cats the knee joint had been inflamed artificially. Recordings from sciatic nerve filaments revealed responses to local mechanical stimulation of the joint in only 3 of 41 group IV units and in 12 of 18 group III units from the normal joint. In the inflamed joint 14 of 36 group IV units and 24 of 36 group III units were excited with local mechanical stimulation. In recordings from dorsal root filaments (normal joint) 4 of 11 group IV units and 7 of 13 group III units were activated by stimulating the joint locally. In the normal joint four group IV units (recorded from dorsal root filaments) responded only to rotations against the resistance of the tissue, whereas the majority of the fibers did not respond even to forceful movements. Group III units with local mechanosensitivity in the normal joint reacted strongly or weakly to movements in the working range of the joint or only to movements against resistance of the tissue. In the inflamed joint, group IV fibers (recorded in sciatic nerve filaments) with detectable receptive fields responded strongly to gentle movements or only to movements against resistance of tissue. Some did not react to movements. Group III units reacted strongly or weakly to gentle movements or only to movements against resistance of the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)


2014 ◽  
Vol 5;17 (5;9) ◽  
pp. E609-E618
Author(s):  
Nebojsa N. Knezevic

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


2015 ◽  
Vol 39 (2) ◽  
pp. 42-46
Author(s):  
Ali Ghanim Al-Okaili

     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.


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