Interaction of NHE1 and TRPA1 activity in DRG neurons isolated from adult rats and its role in inflammatory nociception

Neuroscience ◽  
2021 ◽  
Author(s):  
Vladimir A. Martínez-Rojas ◽  
Ana B. Salinas-Abarca ◽  
Norma L. Gómez-Víquez ◽  
Vinicio Granados-Soto ◽  
Francisco Mercado ◽  
...  
Keyword(s):  
Drg Neurons ◽  
Adult Rats ◽  
Inflammatory Nociception

In Vivo NGF Deprivation Reduces SNS Expression and TTX-R Sodium Currents in IB4-Negative DRG Neurons

1999 ◽  
Vol 81 (2) ◽  
pp. 803-810 ◽  
Author(s):  
Jenny Fjell ◽  
Theodore R. Cummins ◽  
Kaj Fried ◽  
Joel A. Black ◽  
Stephen G. Waxman
Keyword(s):  
Sodium Channel ◽  
Current Density ◽  
Sodium Current ◽  
High Antibody ◽  
Sodium Currents ◽  
Drg Neurons ◽  
Adult Rats ◽  
Antibody Titers

In vivo NGF deprivation reduces SNS expression and TTX-R sodium currents in IB4-negative DRG neurons. Recent evidence suggests that changes in sodium channel expression and localization may be involved in some pathological pain syndromes. SNS, a tetrodotoxin-resistant (TTX-R) sodium channel, is preferentially expressed in small dorsal root ganglion (DRG) neurons, many of which are nociceptive. TTX-R sodium currents and SNS mRNA expression have been shown to be modulated by nerve growth factor (NGF) in vitro and in vivo. To determine whether SNS expression and TTX-R currents in DRG neurons are affected by reduced levels of systemic NGF, we immunized adult rats with NGF, which causes thermal hypoalgesia in rats with high antibody titers to NGF. DRG neurons cultured from rats with high antibody titers to NGF, which do not bind the isolectin IB4 (IB4−) but do express TrkA, were studied with whole cell patch-clamp and in situ hybridization. Mean TTX-R sodium current density was decreased from 504 ± 77 pA/pF to 307 ± 61 pA/pF in control versus NGF-deprived neurons, respectively. In comparison, the mean TTX-sensitive sodium current density was not significantly different between control and NGF-deprived neurons. Quantification of SNS mRNA hybridization signal showed a significant decrease in the signal in NGF-deprived neurons compared with the control neurons. The data suggest that NGF has a major role in the maintenance of steady-state levels of TTX-R sodium currents and SNS mRNA in IB4− DRG neurons in adult rats in vivo.

scholarly journals Estrogen Elicits Dorsal Root Ganglion Axon Sprouting via a Renin-Angiotensin System

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3452-3460 ◽  
Author(s):  
Anuradha Chakrabarty ◽  
Audrey Blacklock ◽  
Stanislav Svojanovsky ◽  
Peter G. Smith
Keyword(s):  
Estrogen Receptor ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Drg Neurons ◽  
Predisposing Factor ◽  
Adult Rats ◽  
Axon Sprouting ◽  
Pain Syndromes

Many painful conditions occur more frequently in women, and estrogen is a predisposing factor. Estrogen may contribute to some pain syndromes by enhancing axon outgrowth by sensory dorsal root ganglion (DRG) neurons. The objective of the present study was to define mechanisms by which estrogen elicits axon sprouting. The estrogen receptor-α agonist propyl pyrazole triol induced neurite outgrowth from cultured neonatal DRG neurons, whereas the estrogen receptor-β agonist diarylpropionitrile was ineffective. 17β-Estradiol (E2) elicited sprouting from peripherin-positive unmyelinated neurons, but not larger NF200-positive myelinated neurons. Microarray analysis showed that E2 up-regulates angiotensin II (ANGII) receptor type 2 (AT2) mRNA in vitro, and studies in adult rats confirmed increased DRG mRNA and protein in vivo. AT2 plays a central role in E2-induced axon sprouting because AT2 blockade by PD123,319 eliminated estrogen-mediated sprouting in vitro. We assessed whether AT2 may be responding to locally synthesized ANGII. DRG from adult rats expressed mRNA for renin, angiotensinogen, and angiotensin converting enzyme (ACE), and protein products were present and occasionally colocalized within neurons and other DRG cells. We determined if locally synthesized ANGII plays a role in estrogen-mediated sprouting by blocking its formation using the ACE inhibitor enalapril. ACE inhibition prevented estrogen-induced neuritogenesis. These findings support the hypothesis that estrogen promotes DRG nociceptor axon sprouting by up-regulating the AT2 receptor, and that locally synthesized ANGII can induce axon formation. Therefore, estrogen may contribute to some pain syndromes by enhancing the pro-neuritogenic effects of AT2 activation by ANGII.

scholarly journals Upregulation of the T-Type Calcium Current in Small Rat Sensory Neurons After Chronic Constrictive Injury of the Sciatic Nerve

2008 ◽  
Vol 99 (6) ◽  
pp. 3151-3156 ◽  
Author(s):  
Miljen M. Jagodic ◽  
Sriyani Pathirathna ◽  
Pavle M. Joksovic ◽  
WooYong Lee ◽  
Michael T. Nelson ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Spinal Ganglia ◽  
Inactivation Kinetics ◽  
Drg Neurons ◽  
Adult Rats ◽  
Pain Transmission ◽  
Chronic Constrictive Injury ◽  
A Charge ◽  
Whole Cell Recordings

Recent data indicate that peripheral T-type Ca2+ channels are instrumental in supporting acute pain transmission. However, the function of these channels in chronic pain processing is less clear. To address this issue, we studied the expression of T-type Ca2+ currents in small nociceptive dorsal root ganglion (DRG) cells from L4-5 spinal ganglia of adult rats with neuropathic pain due to chronic constrictive injury (CCI) of the sciatic nerve. In control rats, whole cell recordings revealed that T-type currents, measured in 10 mM Ba2+ as a charge carrier, were present in moderate density (20 ± 2 pA/pF). In rats with CCI, T-type current density (30 ± 3 pA/pF) was significantly increased, but voltage- and time-dependent activation and inactivation kinetics were not significantly different from those in controls. CCI-induced neuropathy did not significantly change the pharmacological sensitivity of T-type current in these cells to nickel. Collectively, our results indicate that CCI-induced neuropathy significantly increases T-type current expression in small DRG neurons. Our finding that T-type currents are upregulated in a CCI model of peripheral neuropathy and earlier pharmacological and molecular studies suggest that T-type channels may be potentially useful therapeutic targets for the treatment of neuropathic pain associated with partial mechanical injury to the sciatic nerve.

Upregulation of a Silent Sodium Channel After Peripheral, but not Central, Nerve Injury in DRG Neurons

1999 ◽  
Vol 82 (5) ◽  
pp. 2776-2785 ◽  
Author(s):  
J. A. Black ◽  
T. R. Cummins ◽  
C. Plumpton ◽  
Y. H. Chen ◽  
W. Hormuzdiar ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Sodium Channel ◽  
Sodium Channels ◽  
Sodium Current ◽  
Sodium Currents ◽  
Drg Neurons ◽  
Adult Rats ◽  
Voltage Range ◽  
Type Iii ◽  
Axonal Projections

After transection of their axons within the sciatic nerve, DRG neurons become hyperexcitable. Recent studies have demonstrated the emergence of a rapidly repriming tetrodotoxin (TTX)-sensitive sodium current that may account for this hyperexcitability in axotomized small (<27 μm diam) DRG neurons, but its molecular basis has remained unexplained. It has been shown previously that sciatic nerve transection leads to an upregulation of sodium channel III transcripts, which normally are present at very low levels in DRG neurons, in adult rats. We show here that TTX-sensitive currents in small DRG neurons, after transection of their peripheral axonal projections, reprime more rapidly than those in control neurons throughout a voltage range of −140 to −60 mV, a finding that suggests that these currents are produced by a different sodium channel. After transection of the central axonal projections (dorsal rhizotomy) of these small DRG neurons, in contrast, the repriming kinetics of TTX-sensitive sodium currents remain similar to those of control (uninjured) neurons. We also demonstrate, with two distinct antibodies directed against different regions of the type III sodium channel, that small DRG neurons display increased brain type III immunostaining when studied 7–12 days after transection of their peripheral, but not central, projections. Type III sodium channel immunoreactivity is present within somata and neurites of peripherally axotomized, but not centrally axotomized, neurons studied after <24 h in vitro. Peripherally axotomized DRG neurons in situ also exhibit enhanced type III staining compared with control neurons, including an accumulation of type III sodium channels in the distal portion of the ligated and transected sciatic nerve, but these changes are not seen in centrally axotomized neurons. These observations are consistent with a contribution of type III sodium channels to the rapidly repriming sodium currents observed in peripherally axotomized DRG neurons and suggest that type III channels may at least partially account for the hyperexcitibility of these neurons after injury.

Analysis of the long-term actions of gabapentin and pregabalin in dorsal root ganglia and substantia gelatinosa

2014 ◽  
Vol 112 (10) ◽  
pp. 2398-2412 ◽  
Author(s):  
James E. Biggs ◽  
Paul A. Boakye ◽  
Naren Ganesan ◽  
Patrick L. Stemkowski ◽  
Aquilino Lantero ◽  
...  
Keyword(s):  
Dorsal Root ◽  
Substantia Gelatinosa ◽  
Inhibitory Neurons ◽  
Long Term Effects ◽  
Drg Neurons ◽  
Adult Rats ◽  
Postsynaptic Currents ◽  
Excitatory Transmission ◽  
Cell Recording

The α2δ-ligands pregabalin (PGB) and gabapentin (GBP) are used to treat neuropathic pain. We used whole cell recording to study their long-term effects on substantia gelatinosa and dorsal root ganglion (DRG) neurons. Spinal cord slices were prepared from embryonic day 13 rat embryos and maintained in organotypic culture for >5 wk (neuronal age equivalent to young adult rats). Exposure of similarly aged DRG neurons (dissociated and cultured from postnatal day 19 rats) to GBP or PGB for 5–6 days attenuated high-voltage-activated calcium channel currents (HVA ICa). Strong effects were seen in medium-sized and in small isolectin B4-negative (IB4−) DRG neurons, whereas large neurons and small neurons that bound isolectin B4 (IB4+) were hardly affected. GBP (100 μM) or PGB (10 μM) were less effective than 20 μM Mn2+ in suppression of HVA ICa in small DRG neurons. By contrast, 5–6 days of exposure to these α2δ-ligands was more effective than 20 μM Mn2+ in reducing spontaneous excitatory postsynaptic currents at synapses in substantia gelatinosa. Spinal actions of gabapentinoids cannot therefore be ascribed to decreased expression of HVA Ca2+ channels in primary afferent nerve terminals. In substantia gelatinosa, 5–6 days of exposure to PGB was more effective in inhibiting excitatory synaptic drive to putative excitatory neurons than to putative inhibitory neurons. Although spontaneous inhibitory postsynaptic currents were also attenuated, the overall long-term effect of α2δ-ligands was to decrease network excitability as monitored by confocal Ca2+ imaging. We suggest that selective actions of α2δ-ligands on populations of DRG neurons may predict their selective attenuation of excitatory transmission onto excitatory vs. inhibitory neurons in substantia gelatinosa.

Heat-Induced Action Potential Discharges in Nociceptive Primary Sensory Neurons of Rats

2009 ◽  
Vol 102 (1) ◽  
pp. 424-436 ◽  
Author(s):  
Wolfgang Greffrath ◽  
Stefan T. Schwarz ◽  
Dietrich Büsselberg ◽  
Rolf-Detlef Treede
Keyword(s):  
Membrane Potential ◽  
Threshold Current ◽  
Transformation Process ◽  
Drg Neurons ◽  
Adult Rats ◽  
Noxious Heat ◽  
Induced Membrane ◽  
Type 3

Although several transducer molecules for noxious stimuli have been identified, little is known about the transformation of the resulting generator currents into action potentials (APs). Therefore we investigated the transformation process for stepped noxious heat stimuli (42–47°C, 3-s duration) into membrane potential changes and subsequent AP discharges using the somata of acutely dissociated small dorsal root ganglion (DRG) neurons (diameter ≤32.5 μm) of adult rats as a model for their own peripheral terminals. Three types of heat-induced membrane potential changes were differentiated: type 1, heat-induced AP discharges (∼37% of the neurons); type 2, heat-induced membrane depolarization (40%); and type 3, responses not exceeding those of switching the superfusion (23%). Warming neurons from room temperature to 35°C increased their background conductance, nearly doubled the AP threshold current, and led to smaller and narrower APs. Adaptation of heat-induced AP discharges was seen in about half of the type 1 neurons. The remaining half displayed accelerating discharges to both heat stimuli and depolarizing current injection. Repeated heat stimulation induced marked suppression of AP discharges. Under rapid calcium buffering using BAPTA, repolarization of heat-induced APs stopped at a plateau potential slowly decreasing from +16.5 ± 2.9 to −2.2 ± 5.5 mV, resulting in no further AP discharges. This study demonstrates that heat-induced AP discharges can be elicited in the soma of a subgroup of DRG neurons. These discharges display suppression on repetitive stimulation, but either adaptation or sensitization during prolonged stimuli. AP threshold and AP shape during these discharges suggest temperature dependence of background conductance and repolarizing currents.

Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis

2006 ◽  
Vol 291 (3) ◽  
pp. G424-G431 ◽  
Author(s):  
Guang-Yin Xu ◽  
John H. Winston ◽  
Mohan Shenoy ◽  
Huaizhi Yin ◽  
Pankaj Jay Pasricha
Keyword(s):  
Chronic Pancreatitis ◽  
Visceral Pain ◽  
Treated Group ◽  
Fluorescence Labeling ◽  
Intractable Pain ◽  
Type I ◽  
Drg Neurons ◽  
Adult Rats ◽  
Inactivation Curve ◽  
Steady State Inactivation

Chronic pancreatitis (CP) is a relatively common disorder, characterized by glandular insufficiency and chronic, often intractable, pain. The mechanism of pain in CP is poorly understood. We have previously developed a model of trinitrobenzene sulphonic acid (TNBS)-induced CP that results in nociceptive sensitization in rats. This study was designed to examine changes in the excitability and alteration of voltage-gated K+ currents of dorsal root ganglia (DRG) neurons innervating the pancreas. CP was induced in adult rats by an intraductal injection of TNBS. DRG neurons innervating the pancreas were identified by 1,1′-dioleyl-3,3,3′,3-tetramethylindocarbocyanine methanesulfonate fluorescence labeling. Perforated patch-clamp recordings were made from acutely dissociated DRG neurons from control and TNBS-treated rats. Pancreas-specific DRG neurons displayed more depolarized resting potentials in TNBS-treated rats than those in controls ( P < 0.02). Some neurons from the TNBS-treated group exhibited spontaneous firings. TNBS-induced CP also resulted in a dramatic reduction in rheobase ( P < 0.05) and a significant increase in the number of action potentials evoked at twice rheobase ( P < 0.05). Under voltage-clamp conditions, neurons from both groups exhibited transient A-type ( IA) and sustained outward rectifier K+ currents ( IK). Compared with controls, the average IA but not the average IK density was significantly reduced in the TNBS-treated group ( P < 0.05). The steady-state inactivation curve for IA was displaced by ∼20 mV to more hyperpolarized levels after the TNBS treatment. These data suggest that TNBS treatment increases the excitability of pancreas-specific DRG neurons by suppressing IA density, thus identifying for the first time a specific molecular mechanism underlying chronic visceral pain and sensitization in CP.

Further Studies on the Ultrastructure of Harderian Gland in Adult Rats

1974 ◽  
Vol 32 ◽  
pp. 288-289
Author(s):  
Alfredo Feria-Velasco ◽  
Guadalupe Tapia-Arizmendi
Keyword(s):  
Fine Structure ◽  
Domestic Fowl ◽  
Animal Species ◽  
Acinar Cells ◽  
Harderian Gland ◽  
Myoepithelial Cells ◽  
The Other ◽  
Albino Rats ◽  
Adult Rats ◽  
Cell Components

The fine structure of the Harderian gland has been described in some animal species (hamster, rabbit, mouse, domestic fowl and albino rats). There are only two reports in the literature dealing on the ultrastructure of rat Harderian gland in adult animals. In one of them the author describes the myoepithelial cells in methacrylate-embbeded tissue, and the other deals with the maturation of the acinar cells and the formation of the secretory droplets. The aim of the present work is to analize the relationships among the acinar cell components and to describe the two types of cells located at the perifery of the acini.

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