scholarly journals NMDA Receptor Involvement in Neuroplastic Changes Induced By Neonatal Capsaicin Treatment in Trigeminal Nociceptive Neurons

1997 ◽  
Vol 78 (5) ◽  
pp. 2799-2803 ◽  
Author(s):  
Chen Yu Chiang ◽  
James W. Hu ◽  
Barry J. Sessle
Keyword(s):  
Nmda Receptor ◽  
Spontaneous Activity ◽  
Binding Sites ◽  
Nmda Receptor Antagonist ◽  
Adult Rats ◽  
Nociceptive Neurons ◽  
Mk 801 ◽  
Medullary Dorsal Horn ◽  
C Fiber ◽  
Trigeminal Subnucleus Caudalis

Chiang, Chen Yu, James W. Hu, and Barry J. Sessle. NMDA receptor involvement in neuroplastic changes induced by neonatal capsaicin treatment in trigeminal nociceptive neurons. J. Neurophysiol. 78: 2799–2803, 1997. This study examines whether 1) the neonatal loss of C-fiber afferents results in neuroplastic changes in the mechanoreceptive field (RF) properties and spontaneous activity of nociceptive neurons in trigeminal subnucleus caudalis (medullary dorsal horn) of adult rats, and that 2) N-methyl-d-aspartic acid (NMDA) receptor mechanisms are involved in these neuroplastic changes. Compared with vehicle-treated (i.e., control, CON) rats, capsaicin-treated (CAP) rats showed a marked increase in neuronal spontaneous activity and RF size per se, but these neuroplastic changes could be significantly reduced by MK-801 (1 mg/kg, iv), a noncompetitive NMDA receptor antagonist; RF size and spontaneous activity remained unchanged in CON rats after MK-801 administration and in CAP rats after vehicle (saline, iv). Administration of 7-chlorokynurenic acid intrathecally (5 μg/10 μl), an antagonist of strychnine-insensitive glycine binding sites on the NMDA receptor, also significantly reduced neuronal RF size and spontaneous activity in CAP rats, but not in CON rats. These data provide evidence that C-fiber afferents play a role in shaping the properties of nociceptive neurons and that the neuroplastic changes involve NMDA receptor mechanisms.

Effects of GABA Receptor Antagonist on Trigeminal Caudalis Nociceptive Neurons in Normal and Neonatally Capsaicin-Treated Rats

1999 ◽  
Vol 82 (5) ◽  
pp. 2154-2162 ◽  
Author(s):  
Chen Yu Chiang ◽  
Chun L. Kwan ◽  
James W. Hu ◽  
Barry J. Sessle
Keyword(s):  
Receptor Antagonist ◽  
Spontaneous Activity ◽  
Dynamic Range ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Receptor Blockade ◽  
Skin Area ◽  
Adult Rats ◽  
Nociceptive Neurons ◽  
C Fiber

We have recently demonstrated that significant increases in cutaneous mechanoreceptive field (RF) size and spontaneous activity occur in nociceptive neurons of trigeminal subnucleus caudalis (Vc, the medullary dorsal horn) of adult rats depleted of C-fiber afferents by neonatal treatment with capsaicin. These neuronal changes in capsaicin-treated (CAP) rats are suggestive of central neuroplasticity and involve N-methyl-d-aspartic acid (NMDA) receptor mechanisms. The present study examined whether the GABAA receptor antagonist bicuculline (BIC) or the GABAB receptor antagonist 2-hydroxysaclofen (SAC) can influence the RF properties and activity of Vc nociceptive neurons classified as either nociceptive-specific or wide-dynamic range in CAP adult rats or in neonatally vehicle-treated (CON) rats. C-fiber depletion was confirmed in the CAP rats by a significant decrease in plasma extravasation of Evans blue dye in a skin area receiving topical application of mustard oil, a small-fiber excitant and inflammatory irritant. As previously reported, marked increases in cutaneous RF size and spontaneous activity occurred in Vc nociceptive neurons of adult CAP rats, compared with CON rats. GABAA receptor blockade by BIC (i.t.) in CON rats produced a significant increase in spontaneous activity and in pinch RF size and tactile RF size (or appearance of a tactile area in the RF of nociceptive-specific neurons), as well as a significant lowering of the mechanical threshold and a significant enhancement of responses to pinch stimuli applied to the RF. In CAP rats, GABAA receptor blockade also produced significant changes similar to those documented in CON rats, except for a paradoxical and significant decrease in pinch RF size and no noticeable changes in responses to pinch stimuli. GABABreceptor blockade by SAC (i.t.) did not produce any significant changes in Vc nociceptive neurons in either CON or CAP rats. These results suggest that GABAA receptor–mediated inhibition may be involved in maintaining the functional expression of Vc nociceptive neuronal properties in normal conditions, and that in animals depleted of their C-fiber afferents, some features of this GABAAreceptor–mediated modulation may be disrupted such that a GABAA receptor–mediated excitation is manifested.

Neuroplasticity Induced by Tooth Pulp Stimulation in Trigeminal Subnucleus Oralis Involves NMDA Receptor Mechanisms

2001 ◽  
Vol 85 (5) ◽  
pp. 1836-1846 ◽  
Author(s):  
Soo Joung Park ◽  
Chen Yu Chiang ◽  
James W. Hu ◽  
Barry J. Sessle
Keyword(s):  
Nmda Receptor ◽  
Spontaneous Activity ◽  
Emg Activity ◽  
Tooth Pulp ◽  
Mechanical Stimuli ◽  
Nociceptive Neurons ◽  
Mk 801 ◽  
Response Properties ◽  
Mechanical Threshold ◽  
Maxillary Molar

We have recently demonstrated that application of the mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces significant increases in jaw muscle electromyographic (EMG) activity and neuroplastic changes in trigeminal (V) subnucleus caudalis. Since subnucleus oralis (Vo) as well as caudalis receives projections from molar pulp afferents and is also an integral brain stem relay of afferent input from orofacial structures, we tested whether MO application to the exposed pulp induces neuroplastic changes in oralis neurons and whether microinjection of MK-801, a noncompetitive NMDA antagonist, into the Vo influences the pulp/MO-induced neuroplastic changes in chloralose/urethan-anesthetized rats. Single neuronal activity was recorded in Vo, and neurons classified as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR), nociceptive-specific (NS), deep (D), or skin/mucosa and deep (S + D). The spontaneous activity, mechanoreceptive field (RF) size, mechanical threshold, and response to suprathreshold mechanical stimuli applied to the neuronal RF were assessed prior to and throughout a 40- to 60-min period after MO application to the maxillary molar pulp. In animals pretreated with saline microinjection (0.3 μl) into the Vo, MO application to the pulp produced a significant increase in spontaneous activity, expansion of the pinch or deep RF, decrease in the mechanical threshold, and increase in response to suprathreshold mechanical stimuli of the nociceptive (WDR, NS, and S + D) neurons except for those nociceptive neurons having their RF only in the intraoral region. The pulpal application of MO did not produce any significant neuroplastic changes in LTM neurons. Furthermore, in animals pretreated with MK-801 microinjection (3 μg/0.3 μl) into the Vo, MO application to the pulp did not produce any significant changes in the RF and response properties of nociceptive neurons. In other animals pretreated with saline (0.3 μl) or MK-801 (3 μg/0.3 μl) microinjected into the Vo, mineral oil application to the pulp did not produce any significant changes in RF and response properties of nociceptive neurons. These findings indicate that the application of MO to the tooth pulp can induce significant neuroplastic changes in oralis nociceptive neurons and that central NMDA receptor mechanisms may be involved in these neuroplastic changes.

scholarly journals Ketamine Produces a Long-Lasting Enhancement of CA1 Neuron Excitability

2021 ◽  
Vol 22 (15) ◽  
pp. 8091
Author(s):  
Grace Jang ◽  
M. Bruce MacIver
Keyword(s):  
Nmda Receptor ◽  
Potassium Channel ◽  
Receptor Antagonist ◽  
Hippocampal Slices ◽  
Nmda Receptor Antagonist ◽  
Channel Block ◽  
Mk 801 ◽  
Ca1 Region ◽  
Excitatory Transmission ◽  
Ketamine Anesthesia

Ketamine is a clinical anesthetic and antidepressant. Although ketamine is a known NMDA receptor antagonist, the mechanisms contributing to antidepression are unclear. This present study examined the loci and duration of ketamine’s actions, and the involvement of NMDA receptors. Local field potentials were recorded from the CA1 region of mouse hippocampal slices. Ketamine was tested at antidepressant and anesthetic concentrations. Effects of NMDA receptor antagonists APV and MK-801, GABA receptor antagonist bicuculline, and a potassium channel blocker TEA were also studied. Ketamine decreased population spike amplitudes during application, but a long-lasting increase in amplitudes was seen during washout. Bicuculline reversed the acute effects of ketamine, but the washout increase was not altered. This long-term increase was statistically significant, sustained for >2 h, and involved postsynaptic mechanisms. A similar effect was produced by MK-801, but was only partially evident with APV, demonstrating the importance of the NMDA receptor ion channel block. TEA also produced a lasting excitability increase, indicating a possible involvement of potassium channel block. This is this first report of a long-lasting increase in excitability following ketamine exposure. These results support a growing literature that increased GABA inhibition contributes to ketamine anesthesia, while increased excitatory transmission contributes to its antidepressant effects.

The N-Methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) suppresses enfturane-induced opisthotonus in mice

1993 ◽  
Vol 7 (4) ◽  
pp. 520-523 ◽  
Author(s):  
Hisao Komatsu ◽  
Junko Nogaya ◽  
Daisuke Anabuki ◽  
Kenji Ogli
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist ◽  
Mk 801

Role of AMPA/kainate receptors in transmission of the sympathetic baroreflex in rat CVLM

1997 ◽  
Vol 272 (3) ◽  
pp. R800-R812 ◽  
Author(s):  
T. Miyawaki ◽  
S. Suzuki ◽  
J. Minson ◽  
L. Arnolda ◽  
J. Chalmers ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist ◽  
Baroreceptor Reflex ◽  
Significant Inhibition ◽  
Kainate Receptors ◽  
Ventrolateral Medulla ◽  
Mk 801 ◽  
Aortic Nerve

We examined the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors within the caudal ventrolateral medulla (CVLM) in mediating the sympathetic baroreceptor reflex in anesthetized and paralyzed rats. Bilateral microinjection into CVLM of either DL-2-amino-5-phosphonovaleric acid [APV; a selective N-methyl-D-aspartic acid (NMDA) receptor antagonist, 20 mM, 100 nl] or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; a selective AMPA/kainate receptor antagonist, 2 mM, 100 nl) alone failed to eliminate the aortic nerve stimulation-evoked hypotension and inhibition of splanchnic sympathetic nerve activity (SNA) or the cardiac-related rhythmicity of SNA. All components of the sympathetic-baroreceptor reflex were abolished when kynurenate (100 mM, 30 nl) or mixtures of APV and CNQX (10 and 1 mM, respectively, 100 or 30 nl) were injected into CVLM. Injection of APV or CNQX into CVLM reduced aortic nerve-evoked inhibitory responses of bulbospinal sympathoexcitatory neurons in rostral ventrolateral medulla (RVLM). The extent of this reduction was variable. Usually, significant inhibition was preserved. In seven RVLM neurons, intravenous injection of MK-801 (NMDA receptor antagonist, 2 mg/kg) failed to eliminate aortic nerve-evoked inhibitory responses. However, inhibitory responses were abolished when CNQX was injected into CVLM after intravenous MK-801. We conclude that both NMDA and AMPA/kainate receptors in CVLM transmit baroreceptor information.

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