scholarly journals Electrophysiological Identification of Tonic and Phasic Neurons in Sensory Dorsal Root Ganglion and Their Distinct Implications in Inflammatory Pain

2014 ◽  
pp. 793-799 ◽  
Author(s):  
Y.-Q. YU ◽  
X.-F. CHEN ◽  
Y. YANG ◽  
F. YANG ◽  
J. CHEN
Keyword(s):  
Sensory Neurons ◽  
Inflammatory Pain ◽  
Action Potentials ◽  
Dorsal Root ◽  
Dependent Manner ◽  
Primary Sensory Neurons ◽  
Drg Neurons ◽  
Fluorescent Tracer ◽  
Firing Patterns ◽  
Venom Toxin

In the mammalian autonomic nervous system, tonic and phasic neurons can be differentiated on firing patterns in response to long depolarizing current pulse. However, the similar firing patterns in the somatic primary sensory neurons and their functional significance are not well investigated. Here, we identified two types of neurons innervating somatic sensory in rat dorsal root ganglia (DRG). Tonic neurons fire action potentials (APs) in an intensity-dependent manner, whereas phasic neurons typically generate only one AP firing at the onset of stimulation regardless of intensity. Combining retrograde labeling of somatic DRG neurons with fluorescent tracer DiI, we further find that these neurons demonstrate distinct changes under inflammatory pain states induced by complete Freund’s adjuvant (CFA) or bee venom toxin melittin. In tonic neurons, CFA and melittin treatments significantly decrease rheobase and AP durations (depolarization and repolarization), enhance amplitudes of overshoot and afterhyperpolarization (AHP), and increase the number of evoked action potentials. In phasic neurons, however, the same inflammation treatments cause fewer changes in these electrophysiological parameters except for the increased overshoot and decreased AP durations. In the present study, we find that tonic neurons are more hyperexcitable than phasic neurons after peripheral noxious inflammatory stimulation. The results indicate the distinct contributions of two types of DRG neurons in inflammatory pain.

Interaction of opioids and membrane potential to modulate Ca2+ channels in rat dorsal root ganglion neurons

1995 ◽  
Vol 73 (5) ◽  
pp. 1793-1798 ◽  
Author(s):  
M. D. Womack ◽  
E. W. McCleskey
Keyword(s):  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Action Potentials ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
High Threshold ◽  
Partial Recovery ◽  
Drg Neurons ◽  
Ganglion Neurons ◽  
Ca2 Channels

1. Using patch-clamp methods, we show that brief prepulses to very positive voltages increase (facilitate) the amplitude of current through Ca2+ channels during a subsequent test pulse in some, but not all, dorsal root ganglion (DRG) sensory neurons. The amplitude of this facilitated current generally increases when the Ca2+ channels are inhibited by activation of the mu-opioid receptor. 2. The facilitated current is blocked by omega-conotoxin GVIA, activates in the range of high-threshold Ca2+ channels, and inactivates at relatively negative holding voltages. Thus facilitated current passes through N-type Ca2+ channels, the same channels that are inhibited by opioids and control neurotransmitter release in sensory neurons. 3. Although maximal facilitation occurs only at unphysiologically high membrane potentials (above +100 mV), some facilitation is seen after prepulses to voltages reached during action potentials. After return to the holding potential, facilitation persists for hundreds of milliseconds, considerably longer than in other neurons. Brief trains of pulses designed to mimic action potentials caused small facilitation (19% of maximal) in a fraction (8 of 24) of opioid-inhibited neurons. 4. We conclude that 1) prepulses to extremely positive voltages can cause partial recovery of Ca2+ channels inhibited by opioids; and 2) small, but detectable, facilitation is also seen after physiological stimulation in some DRG neurons. Facilitation, largely considered a biophysical epiphenomenon because of the extreme voltages used to induce it, appears to be physiologically relevant during opioid inhibition of Ca2+ channels in DRG neurons.

A-Type Voltage-Gated K+ Currents Influence Firing Properties of Isolectin B4-Positive But Not Isolectin B4-Negative Primary Sensory Neurons

2005 ◽  
Vol 93 (6) ◽  
pp. 3401-3409 ◽  
Author(s):  
Amaresh Vydyanathan ◽  
Zi-Zhen Wu ◽  
Shao-Rui Chen ◽  
Hui-Lin Pan
Keyword(s):  
Sensory Neurons ◽  
Action Potentials ◽  
Neuronal Excitability ◽  
Cell Voltage ◽  
Primary Sensory Neurons ◽  
Drg Neurons ◽  
Voltage Gated ◽  
The Difference ◽  
Firing Properties ◽  
Isolectin B4

Voltage-gated K+ channels (Kv) in primary sensory neurons are important for regulation of neuronal excitability. The dorsal root ganglion (DRG) neurons are heterogeneous, and the types of native Kv currents in different groups of nociceptive DRG neurons are not fully known. In this study, we determined the difference in the A-type Kv current and its influence on the firing properties between isolectin B4 (IB4)-positive and -negative DRG neurons. Whole cell voltage- and current-clamp recordings were performed on acutely dissociated small DRG neurons of rats. The total Kv current density was significantly higher in IB4-positive than that in IB4-negative neurons. Also, 4-aminopyridine (4-AP) produced a significantly greater reduction in Kv currents in IB4-positive than in IB4-negative neurons. In contrast, IB4-negative neurons exhibited a larger proportion of tetraethylammonium-sensitive Kv currents. Furthermore, IB4-positive neurons showed a longer latency of firing and required a significantly larger amount of current injection to evoke action potentials. 4-AP significantly decreased the latency of firing and increased the firing frequency in IB4-positive but not in IB4-negative neurons. Additionally, IB4-positive neurons are immunoreactive to Kv1.4 but not to Kv1.1 and Kv1.2 subunits. Collectively, this study provides new information that 4-AP–sensitive A-type Kv currents are mainly present in IB4-positive DRG neurons and preferentially dampen the initiation of action potentials of this subpopulation of nociceptors. The difference in the density of A-type Kv currents contributes to the distinct electrophysiological properties of IB4-positive and -negative DRG neurons.

ASIC3 and ASIC1 Mediate FMRFamide-Related Peptide Enhancement of H+-Gated Currents in Cultured Dorsal Root Ganglion Neurons

2003 ◽  
Vol 89 (5) ◽  
pp. 2459-2465 ◽  
Author(s):  
Jinghui Xie ◽  
Margaret P. Price ◽  
John A. Wemmie ◽  
Candice C. Askwith ◽  
Michael J. Welsh
Keyword(s):  
Sensory Neurons ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Cation Channels ◽  
Dependent Manner ◽  
Wild Type ◽  
Drg Neurons ◽  
Acid Sensing Ion Channels ◽  
Ganglion Neurons ◽  
Dose Dependent

The acid-sensing ion channels (ASICs) form cation channels that are transiently activated by extracellular protons. They are expressed in dorsal root ganglia (DRG) neurons and in the periphery where they play a function in nociception and mechanosensation. Previous studies showed that FMRFamide and related peptides potentiate H+-gated currents. To better understand this potentiation, we examined the effect of FMRFamide-related peptides on DRG neurons from wild-type mice and animals missing individual ASIC subunits. We found that FMRFamide and FRRFamide potentiated H+-gated currents of wild-type DRG in a dose-dependent manner. They increased current amplitude and slowed desensitization following a proton stimulus. Deletion of ASIC3 attenuated the response to FMRFamide-related peptides, whereas the loss of ASIC1 increased the response. The loss of ASIC2 had no effect on FMRFamide-dependent enhancement of H+-gated currents. These data suggest that FMRFamide-related peptides modulate DRG H+-gated currents through an effect on both ASIC1 and ASIC3 and that ASIC3 plays the major role. The recent discovery of RFamide-related peptides (RFRP) in mammals suggested that they might also modulate H+-gated current. We found that RFRP-1 slowed desensitization of H+-gated DRG currents, whereas RFRP-2 increased the peak amplitude. COS-7 cells heterologously expressing ASIC1 or ASIC3 showed similar effects. These results suggest that FMRFamide-related peptides, including the newly identified RFRPs, modulate H+-gated DRG currents through ASIC1 and ASIC3. The presence of several ASIC subunits, the diversity of FMRFamide-related peptides, and the distinct effects on H+-gated currents suggest the possibility of substantial complexity in modulation of current in DRG sensory neurons.

Expression of Galanin in Rat Primary Sensory Afferents After Moxibustion to the Skin

1992 ◽  
Vol 20 (02) ◽  
pp. 103-114 ◽  
Author(s):  
Hitoshi Kashiba ◽  
Ayahiko Nishigori ◽  
Yoshihiro Ueda
Keyword(s):  
Substance P ◽  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Untreated Control ◽  
Dorsal Root ◽  
Primary Sensory Neurons ◽  
Drg Neurons ◽  
Sensory Afferents ◽  
Retrograde Tracer ◽  
Control Skin

We examined the effects of moxibustion on primary sensory neurons in the skin of rats using immunocytochemistry combined with a fluorescent retrograde tracer dye, fluoro gold (FG). Galanin-like immunoreactive (IR) fibers were often observed in the dermis of treated skin at 18 hours after moxibustion, while such fibers were rarely detected in untreated (control) skin. Moreover, most of galanin-IR fibers also displayed substance P(SP)-like immunoreactivity. About 20-30% of the dorsal root ganglion (DRG) neurons labeled when FG was injected intradermally into the moxibustion-treated skin showed galanin-like immunoreactivity, while the proportion of FG-labeled neurons with such immunoreactivity was < 10% in control DRGs. These results show that moxibustion induced galanin expression by primary sensory neurons containing SP. The possible functions of this peptide are discussed in relation to the effects of moxibustion.

scholarly journals Inhibition of Hyperpolarization-Activated Cation Current in Medium-Sized DRG Neurons Contributed to the Antiallodynic Effect of Methylcobalamin in the Rat of a Chronic Compression of the DRG

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Ming Zhang ◽  
Wenjuan Han ◽  
Jianyong Zheng ◽  
Fancheng Meng ◽  
Xiying Jiao ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Analgesic Effect ◽  
Dorsal Root ◽  
High Dose ◽  
Dependent Manner ◽  
Drg Neurons ◽  
Continuous Application

Recently several lines of evidence demonstrated that methylcobalamin (MeCbl) might have potential analgesic effect in experimental and clinical studies. However, it was reported that MeCbl had no effect on treating lumbar spinal stenosis induced pain. Thus, the effects of short-term and long-term administration of MeCbl were examined in the chronic compression of dorsal root ganglion (CCD) model. We found that mechanical allodynia was significantly inhibited by a continuous application of high dose and a single treatment of a super high dose of MeCbl. Little is known about mechanisms underlying the analgesia of MeCbl. We examined the effect of MeCbl on the spontaneous activity (SA), the excitability, and hyperpolarization-activated nonselective cation ion current in compressed medium-sized dorsal root ganglion (DRG) neurons using extracellular single fiber recordingin vivoand whole-cell patch clampin vitro. We found that MeCbl significantly inhibited the SA of A-type sensory neurons in a dose-dependent manner and inhibited the excitability of medium-sized DRG neurons. In addition, MeCbl also decreasedIhcurrent density in injured medium-sized DRG neurons. Our results proved that MeCbl might exert an analgesic effect through the inhibitionIhcurrent and then might inhibit the hyperexcitability of primary sensory neurons under neuropathic pain state.

Inhibition of Rapid Heat Responses in Nociceptive Primary Sensory Neurons of Rats by Vanilloid Receptor Antagonists

1999 ◽  
Vol 82 (6) ◽  
pp. 2853-2860 ◽  
Author(s):  
Timo Kirschstein ◽  
Wolfgang Greffrath ◽  
Dietrich Büsselberg ◽  
Rolf-Detlef Treede
Keyword(s):  
Sensory Neurons ◽  
Reversal Potential ◽  
Vanilloid Receptor ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Primary Sensory Neurons ◽  
Drg Neurons ◽  
Patch Clamp Technique ◽  
Noxious Heat ◽  
Duration Of Action

Recent studies demonstrated that heat-sensitive nociceptive primary sensory neurons respond to the vanilloid receptor (VR) agonist capsaicin, and the first cloned VR is a heat-sensitive ion channel. Therefore we studied to what extent heat-evoked currents in nociceptive dorsal root ganglion (DRG) neurons can be attributed to the activation of native vanilloid receptors. Heat-evoked currents were investigated in 89 neurons acutely dissociated from adult rat DRGs as models for their own terminals using the whole cell patch-clamp technique. Locally applied heated extracellular solution (effective temperature ∼53°C) rapidly activated reversible and reproducible inward currents in 80% (62/80) of small neurons (≤32.5 μm), but in none of nine large neurons ( P < 0.001, χ2 test). Heat and capsaicin sensitivity were significantly coexpressed in this subpopulation of small DRG neurons ( P < 0.001, χ2 test). Heat-evoked currents were accompanied by an increase of membrane conductance (320 ± 115%; mean ± SE, n = 7), had a reversal potential of 5 ± 2 mV ( n = 5), which did not differ from that of capsaicin-induced currents in the same neurons (4 ± 3 mV), and were carried at least by Na+ and Ca2+(pCa2+ > pNa+). These observations are consistent with the opening of temperature-operated nonselective cation channels. The duration of action potentials was significantly higher in heat-sensitive (10–90% decay time: 4.45 ± 0.39 ms, n = 12) compared with heat-insensitive neurons (2.18 ± 0.19 ms, n = 6; P< 0.005, Student's t-test), due to an inflection in the repolarizing phase. This property as well as capsaicin sensitivity and small cell size are characteristics of nociceptive DRG neurons. When coadministered with heat stimuli, the competitive VR antagonist capsazepine (1 μM to 1 mM) significantly reduced heat-evoked currents in a dose-dependent manner (IC50 13 μM, Hill slope −0.58, maximum effect 75%). Preincubation for 12–15 s shifted the IC50 by ∼0.5 log10 units to an estimated IC50 of ∼4 μM. The noncompetitive VR antagonist ruthenium red (5 μM) significantly reduced heat-evoked currents by 33 ± 6%. The effects of both VR antagonists were rapidly reversible. Our results provide evidence for a specific activation of native VRs in nociceptive primary sensory neurons by noxious heat. The major proportion of the rapid heat-evoked currents can be attributed to the activation of these temperature-operated channels, and noxious heat may be the signal detected by VRs under physiological conditions.

scholarly journals Glutaminase Immunoreactivity and Enzyme Activity Is Increased in the Rat Dorsal Root Ganglion Following Peripheral Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kenneth E. Miller ◽  
John C. Balbás ◽  
Richard L. Benton ◽  
Travis S. Lam ◽  
Kristin M. Edwards ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Dorsal Root Ganglion ◽  
Western Blot ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Peripheral Sensitization ◽  
Primary Sensory Neurons ◽  
Drg Neurons ◽  
Glutamate Production ◽  
Afferent Terminals

Following inflammation, primary sensory neurons in the dorsal root ganglion (DRG) alter the production of several proteins. Most DRG neurons are glutamatergic, using glutaminase as the enzyme for glutamate production, but little is known about glutaminase following inflammation. In the present study, adjuvant-induced arthritis (AIA) was produced in rats with complete Freund's adjuvant into the hindpaw. At 7 days of AIA, DRG were examined with glutaminase immunohistochemistry, Western blot immunoreactivity, and enzyme activity. Image analysis revealed that glutaminase was elevated most in small-sized neurons (21%) (P < 0.05). Western blot analysis revealed a 19% increase (P < 0.05) in total glutaminase and 21% in mitochondrial glutaminase (P < 0.05). Glutaminase enzyme activity was elevated 29% (P < 0.001) from 2.20 to 2.83 moles/kg/hr. Elevated glutaminase in primary sensory neurons could lead to increased glutamate production in spinal primary afferent terminals contributing to central sensitization or in the peripheral process contributing to peripheral sensitization.

Dorsal Root Ganglion Neuron Types and Their Functional Specialization

2018 ◽  
pp. 127-155 ◽  
Author(s):  
Edward C. Emery ◽  
Patrik Ernfors
Keyword(s):  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Drg Neurons ◽  
Low Threshold

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.

scholarly journals ATP metabolizing enzymes ENPP1, 2 and 3 are localized in sensory neurons of rat dorsal root ganglion

2018 ◽  
Author(s):  
Kentaro Nishida ◽  
Yuka Nomura ◽  
Kanako Kawamori ◽  
Akihiro Ohishi ◽  
Kazuki Nagasawa
Keyword(s):  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Adenine Nucleotide ◽  
Expression Profiles ◽  
Critical Role ◽  
Immunohistochemical Analysis ◽  
Uptake System ◽  
Nucleoside Transporter ◽  
Drg Neurons

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.

scholarly journals Cytotoxic Effect of Commercially Available Methylprednisolone Acetate with and without Reduced Preservatives on Dorsal Root Ganglion Sensory Neurons in Rats

2014 ◽  
Vol 5;17 (5;9) ◽  
pp. E609-E618
Author(s):  
Nebojsa N. Knezevic
Keyword(s):  
Polyethylene Glycol ◽  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Cytotoxic Effect ◽  
Caspase 3 ◽  
Tunel Assay ◽  
Methylprednisolone Acetate ◽  
Drg Neurons ◽  
Isolated Rat

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

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