scholarly journals Presynaptic and Postsynaptic Effects of the Anesthetics Sevoflurane and Nitrous Oxide in the Human Spinal Cord

2007 ◽  
Vol 107 (4) ◽  
pp. 553-562 ◽  
Author(s):  
Jan H. Baars ◽  
Michael Benzke ◽  
Falk von Dincklage ◽  
Josephine Reiche ◽  
Peter Schlattmann ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nitrous Oxide ◽  
Presynaptic Inhibition ◽  
Femoral Nerve ◽  
Volatile Anesthetic ◽  
H Reflex ◽  
Receptor Subtype ◽  
Gamma Aminobutyric Acid ◽  
Human Spinal Cord ◽  
Two Parameters

Background Reduced spinal excitability contributes to the suppression of movement responses to noxious stimuli during the anesthetic state. This study examines and compares presynaptic and postsynaptic effects of two anesthetics in the human spinal cord. Methods The authors tested two parameters during the administration of 0.8 vol% sevoflurane or 40 vol% nitrous oxide compared with control states before and after drug administration: (1) the size of the soleus H reflex (integrating presynaptic and postsynaptic effects) at increasing stimulus intensities (recruitment curve) and (2) the amount of presynaptic inhibition on Ia afferents of the quadriceps femoris, evaluated by the heteronymous facilitation of the soleus H reflex caused by a conditioning stimulation of the femoral nerve. The study was performed in 10 subjects for each drug. Results At the chosen concentrations, the maximum H reflex was reduced by 26.3 +/- 8.4% (mean +/- SD) during sevoflurane and by 33.5 +/- 15.6% during nitrous oxide administration. The averaged recruitment curves were similarly depressed under the influence of the two drugs. The reduction of H-reflex facilitation was significantly stronger for sevoflurane (28.8 +/- 20.0%) than for nitrous oxide administration (6.2 +/- 26.4%). Conclusions These results demonstrate in humans presynaptic effects of the volatile anesthetic sevoflurane but not of nitrous oxide. A possible explanation for this difference may be the different potency of the respective drugs in enhancing gamma-aminobutyric acid type A receptor-mediated inhibition, because presynaptic inhibition in the spinal cord involves this receptor subtype.

Propofol Increases Presynaptic Inhibition of Ia Afferents in the Intact Human Spinal Cord

2006 ◽  
Vol 104 (4) ◽  
pp. 798-804 ◽  
Author(s):  
Jan H. Baars ◽  
Falk von Dincklage ◽  
Josephine Reiche ◽  
Benno Rehberg
Keyword(s):  
Spinal Cord ◽  
Tibial Nerve ◽  
Femoral Nerve ◽  
Conditioning Stimulus ◽  
Type A ◽  
H Reflex ◽  
Excitatory Postsynaptic Potential ◽  
Human Spinal Cord ◽  
Ia Afferents ◽  
Stimulation Of

Background In vitro studies indicate that the primary molecular targets of propofol in the spinal cord are gamma-aminobutyric acid (GABA) type A receptors. Because of the complexity of the central nervous system, specific GABA-mediated effects have not yet been isolated in humans. Here, the authors used heteronymous Ia facilitation of the soleus H-reflex from the femoral nerve as a specific pathway involving GABA to demonstrate a presynaptic GABA-mediated effect of propofol in humans. Methods The study was performed in 10 volunteers aged 23-32 yr. The soleus H-reflex was evoked by stimulation of the tibial nerve in the popliteal fossa. The stimulation current was adjusted to yield an unconditioned H-reflex of 15% of the maximal muscle response to electric stimulation of the tibial nerve. The soleus H-reflex was conditioned by stimulating Ia afferents from the quadriceps femoris in the femoral triangle. The stimulus was applied 0.3-0.4 ms after the onset of facilitation, to assure a purely monosynaptic excitatory postsynaptic potential from quadriceps Ia afferents to the soleus motoneuron. At least 45 conditioned (femoral and tibial) and unconditioned (only tibial) stimuli were applied in random order. The authors compared the amount of heteronymous H-reflex facilitation under a concentration of 2 microg/ml propofol with control values obtained before and after the propofol infusion. Results H-reflex facilitation due to the conditioning stimulus during propofol administration was significantly (P < 0.05, t test) decreased by an average of 43% in all patients in comparison with the control values. Conclusions Although alternative explanations such as supraspinal effects cannot be ruled out completely, the findings of this study are most likely explained by a specific presynaptic effect of propofol. Strong evidence form neurophysiologic studies indicates that this effect is mediated by the GABA type A receptors.

Spinal Cord Motoneuron Excitability during Isoflurane and Nitrous Oxide Anesthesia

1997 ◽  
Vol 86 (2) ◽  
pp. 302-307 ◽  
Author(s):  
Henry H. Zhou ◽  
Mahesh Mehta ◽  
Arturo A. Leis
Keyword(s):  
Spinal Cord ◽  
Nitrous Oxide ◽  
Wave Amplitude ◽  
Specific Effect ◽  
H Reflex ◽  
Reflex Amplitude ◽  
Isoflurane Concentration ◽  
Human Spinal Cord ◽  
Motoneuron Excitability ◽  
F Wave

Background Recent evidence suggests that the spinal cord is an important site of anesthesia that is necessary for surgical immobility, but the specific effect of anesthetics within the spinal cord is unclear. This study assessed the effect of isoflurane and nitrous oxide on spinal motoneuron excitability by monitoring the H-reflex and the F wave. Methods Eight adult patients, categorized as American Society of Anesthesiologists physical status 1 or 2, who were undergoing elective orthopaedic surgery were anesthetized with 0.6, 0.8, 1.0, and 1.2 times the estimated minimum alveolar concentration (MAC) of isoflurane. Nitrous oxide was added in graded concentrations of 30%, 50%, and 70%, whereas the isoflurane concentration was decreased to maintain a total MAC of 1. The H-reflex of the soleus muscle and the F wave of the abductor hallucis muscle were measured before anesthesia and 15 min after each change of anesthetic concentration. Four or more trials of the H-reflex and 18 trials of the F wave were recorded at each concentration of anesthesia. The effect of the anesthetics on the H-reflex and F wave was analyzed using. Dunnett's test. Results H-reflex amplitude was decreased to 48.4 +/- 18.6% of preanesthesia level at 0.6 MAC isoflurane and to 33.8 +/- 19.1% when isoflurane concentration increased from 0.6 MAC to 1.2 MAC. F wave amplitude and persistence decreased to 52.2 +/- 33.6% and 44.4 +/- 26% of baseline at 0.6 MAC isoflurane, and to 33.8 +/- 26% and 21.7 +/- 22.8% at 1.2 MAC isoflurane. Isoflurane plus nitrous oxide (total 1 MAC) decreased H-reflex amplitude to 30.4-33.3% and decreased F wave persistence to 42.8-56.3% of baseline. Conclusions Both isoflurane alone and isoflurane plus nitrous oxide decrease H-reflex and F-wave amplitude and F-wave persistence. These effects suggest that isoflurane and nitrous oxide decrease motoneuronal excitability in the human spinal cord. This may play an important role in producing surgical immobility.

Divergence of Volatile Anesthetic Effects in Inhibitory Neurotransmitter Receptors

2001 ◽  
Vol 94 (6) ◽  
pp. 1026-1033 ◽  
Author(s):  
Eric P. Greenblatt ◽  
Xin Meng
Keyword(s):  
Gaba Receptor ◽  
Functional Divergence ◽  
Volatile Anesthetic ◽  
Silent Mutation ◽  
Receptor Subtype ◽  
Gamma Aminobutyric Acid ◽  
Inhibitory Neurotransmitter ◽  
Multiple Protein ◽  
Unique Restriction ◽  
First Time

Background The mechanism of volatile anesthetic (VA) action is unknown. Inhibitory receptors for the neurotransmitters gamma-aminobutyric acid (GABA) or glycine are typically positively modulated by VAs and may be important targets for their action. The existence of a GABA receptor subtype (p), which is uniquely inhibited by VAs, suggested a chimeric receptor approach to identify portions of these proteins that may be necessary for anesthetic effects. Methods A silent mutation resulting in the addition of a unique restriction enzyme recognition site was introduced in GABA receptor type A alpha2, glycine alpha1, and p subunit cDNAs. Chimeras were constructed by rejoining restriction digest fragments and were expressed in Xenopus oocytes. Modulation of submaximal agonist-evoked peak currents by the VAs chloroform, enflurane, halothane, or isoflurane was measured using two-electrode voltage clamp. Results Four chimeras were constructed and designated glyrho, rhogly, alpha2rho, and rhoalpha2. Glyrho formed glycine-gated receptors with currents that were enhanced by chloroform or halothane but were inhibited by enflurane or isoflurane. Chimeras rhogly and rhoalpha2 each formed GABA-gated receptors with currents that were inhibited by chloroform or halothane but enhanced by enflurane or isoflurane. Conclusions These data show, for the first time, functional divergence of VA action on a single protein target. The VAs in this study fall into two distinct groups with respect to their effects on these receptors. This grouping parallels the chemistry of these compounds. Our results support the involvement of multiple protein domains in the mechanism of VA modulation of GABA and glycine receptors.

Propofol enhances GABAA receptor-mediated presynaptic inhibition in human spinal cord

Neuroreport ◽  
2002 ◽  
Vol 13 (3) ◽  
pp. 357-360 ◽  
Author(s):  
Miyako Shimizu ◽  
Tomohiro Yamakura ◽  
Toshiyuki Tobita ◽  
Manabu Okamoto ◽  
Toyofumi Ataka ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gabaa Receptor ◽  
Presynaptic Inhibition ◽  
Human Spinal Cord

scholarly journals The Effect of Diazepam on Presynaptic Inhibition in Patients with Complete and Incomplete Spinal Cord Lesions

1975 ◽  
Vol 2 (3) ◽  
pp. 179-184 ◽  
Author(s):  
M. Verrier ◽  
S. MacLeod ◽  
P. Ashby
Keyword(s):  
Spinal Cord ◽  
Presynaptic Inhibition ◽  
H Reflex ◽  
Inhibitory Mechanism ◽  
Spinal Cord Lesions ◽  
Spinal Lesions

SUMMARY:The effect of diazepam on presynaptic inhibition in man has been examined in 5 patients with complete spinal transections and 7 patients with incomplete lesions. The inhibition of the H reflex by vibration applied to the tendo Achilles was used to assess presynaptic inhibition of the la monosynaptic pathway. Diazepam increased this inhibition in the patients with incomplete lesions, but had no significant effect on the inhibition in the patients with complete spinal transections.Evidently diazepam can enhance presynaptic inhibition in man. The effect, however, cannot be demonstrated in patients with longstanding complete spinal lesions possibly because of some alteration in the segmental presynaptic inhibitory mechanism in this group.

α-2A Is the Predominant α-2 Adrenergic Receptor Subtype in Human Spinal Cord

1992 ◽  
Vol 77 (5) ◽  
pp. 983-991 ◽  
Author(s):  
Robert G. Lawhead ◽  
Howard S. Blaxall ◽  
David B. Bylund
Keyword(s):  
Spinal Cord ◽  
Adrenergic Receptor ◽  
Receptor Subtype ◽  
Human Spinal Cord

scholarly journals Neurophysiological Changes After Paired Brain and Spinal Cord Stimulation Coupled With Locomotor Training in Human Spinal Cord Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Timothy S. Pulverenti ◽  
Morad Zaaya ◽  
Monika Grabowski ◽  
Ewelina Grabowski ◽  
Md. Anamul Islam ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Cortex ◽  
Stance Phase ◽  
Training Session ◽  
H Reflex ◽  
Locomotor Training ◽  
Step Cycle ◽  
Human Spinal Cord ◽  
Cord Injury

Neurophysiological changes that involve activity-dependent neuroplasticity mechanisms via repeated stimulation and locomotor training are not commonly employed in research even though combination of interventions is a common clinical practice. In this randomized clinical trial, we established neurophysiological changes when transcranial magnetic stimulation (TMS) of the motor cortex was paired with transcutaneous thoracolumbar spinal (transspinal) stimulation in human spinal cord injury (SCI) delivered during locomotor training. We hypothesized that TMS delivered before transspinal (TMS-transspinal) stimulation promotes functional reorganization of spinal networks during stepping. In this protocol, TMS-induced corticospinal volleys arrive at the spinal cord at a sufficient time to interact with transspinal stimulation induced depolarization of alpha motoneurons over multiple spinal segments. We further hypothesized that TMS delivered after transspinal (transspinal-TMS) stimulation induces less pronounced effects. In this protocol, transspinal stimulation is delivered at time that allows transspinal stimulation induced action potentials to arrive at the motor cortex and affect descending motor volleys at the site of their origin. Fourteen individuals with motor incomplete and complete SCI participated in at least 25 sessions. Both stimulation protocols were delivered during the stance phase of the less impaired leg. Each training session consisted of 240 paired stimuli delivered over 10-min blocks. In transspinal-TMS, the left soleus H-reflex increased during the stance-phase and the right soleus H-reflex decreased at mid-swing. In TMS-transspinal no significant changes were found. When soleus H-reflexes were grouped based on the TMS-targeted limb, transspinal-TMS and locomotor training promoted H-reflex depression at swing phase, while TMS-transspinal and locomotor training resulted in facilitation of the soleus H-reflex at stance phase of the step cycle. Furthermore, both transspinal-TMS and TMS-transspinal paired-associative stimulation (PAS) and locomotor training promoted a more physiological modulation of motor activity and thus depolarization of motoneurons during assisted stepping. Our findings support that targeted non-invasive stimulation of corticospinal and spinal neuronal pathways coupled with locomotor training produce neurophysiological changes beneficial to stepping in humans with varying deficits of sensorimotor function after SCI.

Mechanisms modulating spinal excitability after nerve stimulation inducing extra torque

2021 ◽  
Author(s):  
Florian Vitry ◽  
Maria Papaiordanidou ◽  
Alain Martin
Keyword(s):  
Nerve Stimulation ◽  
Presynaptic Inhibition ◽  
Motor Evoked Potentials ◽  
Femoral Nerve ◽  
Common Peroneal Nerve ◽  
H Reflex ◽  
Ia Afferents ◽  
Thoracic Level ◽  
The Common ◽  
Spinal Excitability

The study included 3 experiments aiming to examine the mechanisms responsible for spinal excitability modulation, as assessed by the H-reflex, following stimulation trains delivered at two different frequencies (20 and 100Hz) inducing extra torque (ET). A first experiment (n=15) was conducted to evaluate changes in presynaptic inhibition acting on Ia afferents induced by these electrical stimulation trains, assessed by conditioning the soleus H-reflex (tibial nerve stimulation) with stimulation of the common peroneal nerve (D1 inhibition) and of the femoral nerve (heteronymous Ia facilitation, HF). A second experiment (n=12) permitted to investigate homosynaptic post-activation depression (HPAD) changes after the stimulation trains. A third experiment (n=14) analysed changes in motoneuron intrinsic properties after the stimulation trains, by electrically stimulating the descending corticospinal tract at the thoracic level, evoking thoracic motor evoked potentials (TMEP). Main results showed that in all experiments spinal excitability decreased after the 20-Hz train (P<0.05), while this parameter significantly increased after the 100-Hz stimulation (P<0.05). D1 and HF were not significantly modified after either stimulation. HPAD was significantly decreased only after the 20-Hz train, while TMEP was significantly increased only after the 100-Hz train (P<0.05). It is concluded that the decreased spinal excitability observed after the 20-Hz train cannot be attributed to D1 presynaptic inhibition but rather to increased HPAD of the Ia afferents terminals, while the increase of this parameter obtained after the 100-Hz train can be assigned to changes in intrinsic motoneuron properties allowing to maintain Ia - alpha motoneurons transmission efficacy.

GABAergic Interneurons at Supraspinal and Spinal Levels Differentially Modulate the Antinociceptive Effect of Nitrous Oxide in Fischer Rats

2003 ◽  
Vol 98 (5) ◽  
pp. 1223-1230 ◽  
Author(s):  
Ryo Orii ◽  
Yoko Ohashi ◽  
Sunil Halder ◽  
Mariangela Giombini ◽  
Mervyn Maze ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nitrous Oxide ◽  
Antinociceptive Effect ◽  
Gabaergic Neurons ◽  
Inhibitory Neurons ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Fischer Rats ◽  
The Brain ◽  
Gas Exposure

Background The study hypothesizes that nitrous oxide (N(2)O) releases opioid peptide in the brain stem, which results in inhibition of gamma-aminobutyric acid-mediated (GABAergic) neurons that tonically inhibit the descending noradrenergic inhibitory neurons (DNIN), resulting in activation of DNIN. In the spinal cord, activation of DNIN leads to the release of norepinephrine, which inhibits nociceptive processing through direct activation of alpha2 adrenoceptor and indirect activation of GABAergic neurons through alpha1 adrenoceptor. Arising from this hypothesis, it follows that GABAergic neurons will modulate the antinociceptive effect of N(2)O in diametrically opposite directions at supraspinal and spinal levels. The authors have tested this tenet and further examined the effect of midazolam, a GABA-mimetic agent, on N(2)O-induced antinociceptive effect. Methods Adult male Fischer rats were administered muscimol (GABA(A) receptor agonist) intracerebroventricularly (icv), gabazine (GABA(A) receptor antagonist) intrathecally (intrathecal), or midazolam intraperitoneally (intraperitoneal). Fifteen minutes later, they were exposed to air or 75% N(2)O and were subjected to the plantar test after 30 min of gas exposure. In some animals administered with midazolam, gas exposure was continued for 90 min, and the brain and spinal cord were examined immunohistochemically. Results The N(2)O-induced antinociceptive effect, which was attenuated by icv muscimol, intrathecal gabazine, and intraperitoneal midazolam. Midazolam inhibited N(2)O-induced c-Fos expression (a marker of neuronal activation) in the pontine A7 and spinal cord. Conclusions The GABAergic neurons modulate the antinociceptive effect of N(2)O in opposite directions at supraspinal and spinal levels. The pronociceptive effects of enhancement at the supraspinal GABAergic site predominate in response to systemically administered midazolam.

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