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

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.

2007 ◽  
Vol 107 (4) ◽  
pp. 553-562 ◽  
Author(s):  
Jan H. Baars ◽  
Michael Benzke ◽  
Falk von Dincklage ◽  
Josephine Reiche ◽  
Peter Schlattmann ◽  
...  

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.


2013 ◽  
Vol 109 (8) ◽  
pp. 2118-2128 ◽  
Author(s):  
Patrick M. Sonner ◽  
David R. Ladle

Sensory feedback is critical for normal locomotion and adaptation to external perturbations during movement. Feedback provided by group Ia afferents influences motor output both directly through monosynaptic connections and indirectly through spinal interneuronal circuits. For example, the circuit responsible for reciprocal inhibition, which acts to prevent co-contraction of antagonist flexor and extensor muscles, is driven by Ia afferent feedback. Additionally, circuits mediating presynaptic inhibition can limit Ia afferent synaptic transmission onto central neuronal targets in a task-specific manner. These circuits can also be activated by stimulation of proprioceptive afferents. Rodent locomotion rapidly matures during postnatal development; therefore, we assayed the functional status of reciprocal and presynaptic inhibitory circuits of mice at birth and compared responses with observations made after 1 wk of postnatal development. Using extracellular physiological techniques from isolated and hemisected spinal cord preparations, we demonstrate that Ia afferent-evoked reciprocal inhibition is as effective at blocking antagonist motor neuron activation at birth as at 1 wk postnatally. In contrast, at birth conditioning stimulation of muscle nerve afferents failed to evoke presynaptic inhibition sufficient to block functional transmission at synapses between Ia afferents and motor neurons, even though dorsal root potentials could be evoked by stimulating the neighboring dorsal root. Presynaptic inhibition at this synapse was readily observed, however, at the end of the first postnatal week. These results indicate Ia afferent feedback from the periphery to central spinal circuits is only weakly gated at birth, which may provide enhanced sensitivity to peripheral feedback during early postnatal experiences.


Author(s):  
O. Kolosova

The purpose of our work was to investigate in detail the influence of pair stimulation of tibial nerve (n.tibialis) on human soleus H-reflex amplitude at rest and after long-lasting voluntary contraction of calf muscle (m.m. gastrocnemius-soleus), which caused the fatigue of soleus muscle. The method of H-reflex of soleus muscle was used. Test and conditioned responses (by pair stimulation of n. tibialis) were registered. Homosynaptic postactivation depression led to inhibition of H-reflex at rest. After fatiguing voluntary static contraction the amplitudes of test and conditioned soleus H-reflex were significantly reduced. Then both H-reflex amplitudes subsequently recovered. Soleus H-reflex inhibition might be due to the activation of the groups III and IV afferent nerves under the influence of mechanical and metabolic changes in the muscle.


2007 ◽  
Vol 98 (2) ◽  
pp. 878-887 ◽  
Author(s):  
Xiang Yang Chen ◽  
Shreejith Pillai ◽  
Yi Chen ◽  
Yu Wang ◽  
Lu Chen ◽  
...  

Sensorimotor cortex (SMC) modifies spinal cord reflex function throughout life and is essential for operant conditioning of the H-reflex. To further explore this long-term SMC influence over spinal cord function and its possible clinical uses, we assessed the effect of long-term SMC stimulation on the soleus H-reflex. In freely moving rats, the soleus H-reflex was measured 24 h/day for 12 wk. The soleus background EMG and M response associated with H-reflex elicitation were kept stable throughout. SMC stimulation was delivered in a 20-day-on/20-day-off/20-day-on protocol in which a train of biphasic 1-ms pulses at 25 Hz for 1 s was delivered every 10 s for the on-days. The SMC stimulus was automatically adjusted to maintain a constant descending volley. H-reflex size gradually increased during the 20 on-days, stayed high during the 20 off-days, and rose further during the next 20 on-days. In addition, the SMC stimulus needed to maintain a stable descending volley rose steadily over days. It fell during the 20 off-days and rose again when stimulation resumed. These results suggest that SMC stimulation, like H-reflex operant conditioning, induces activity-dependent plasticity in both the brain and the spinal cord and that the plasticity responsible for the H-reflex increase persists longer after the end of SMC stimulation than that underlying the change in the SMC response to stimulation.


2012 ◽  
Vol 27 (3) ◽  
pp. 260-268 ◽  
Author(s):  
Colin K. Franz ◽  
Bhagat Singh ◽  
Jose A. Martinez ◽  
Douglas W. Zochodne ◽  
Rajiv Midha

2019 ◽  
Vol 12 (2) ◽  
pp. 50-64
Author(s):  
George Elesnitsalis ◽  
Ioannis Amiridis ◽  
Dimitrios Patikas ◽  
Ioanna Vekili ◽  
Maria Vourvou

Introduction: Polyneuromyopathy constitutes a common complication in critically ill patients of the Intensive Care Unit (ICU) and in the last few years it appears to be identified as a syndrome detectable in the limbs and respiratory muscles. It is associated with the difficulties during weaning from mechanical ventilation. Aim: The present study investigates the reflective reaction of the soleus muscle following an electrical stimulation of the tibial nerve in intubated critically ill patients hospitalized in ICU with no medical history prior to their admission. Methods: Thirteen (13) patients who had been hospitalized for more than five (5) days and had a high APACHE II score (>15) and 13 age-matched control subjects were asked to participate in the present study on a volunteer basis. During the study, as reflective response parameters the range of the H-reflex and M-wave of the soleus muscle, as well as the conduction velocity of the tibial nerve, after electro-stimulation of the tibial nerve at the popliteal-fossa level, were assessed Results: Statistical analysis revealed significantly lower values in the ICU patients compared to healthy controls in both H-reflex range (p<0,049) and the M-wave range (p<0,041), as well as conduction velocity (p<0,001) of the tibial nerve. Conclusions: It is concluded that the reflective response of the soleus muscle as well as the tibial nerve’s conduction velocity are affected in critically ill patients hospitalized in ICU. The study of the above neurological parameters can provide further insights into the establishment and progress of polyneuromyopathy of critically ill patients in ICUs.


2014 ◽  
Vol 6 (1) ◽  
Author(s):  
Joanna Mazur–Różycka ◽  
Jan Gajewski ◽  
Krzysztof Buśko ◽  
Radosław Michalski ◽  
Patrycja Łach

Summary Study aim: to evaluate the differences in H-reflex parameters in lying and standing positions in canoeists. Material and methods: twenty seven male canoeists (age 17.2 ± 1.6 year, body mass 73.7 ± 7.6 kg, height 180.9 ± 6.1 cm, training experience 6.5 ± 3.6 years) participated in the study. None of the subjects had any history of neuromuscular disorders. The soleus H-reflex was examined in each subject twice: in lying and standing position. H-reflex was elicited by one-millisecond electrical stimulation of a posterior tibial nerve in the popliteal fossa. A recruitment curve for each subject was obtained by gradually increasing the stimulus intensity. Results: the results obtained in the present study showed statistically significant differences of the variables characterising effects of stimulations performed in lying and standing positions (F4,23 = 8.063; p < 0.001). H/M ratio was 0.50 ± 0.25 and 0.64 ± 0.27 for lying and standing positions, respectively. Our results support previous findings. Conclusions: the lying position is recommended for measurements as more comfortable for subjects and providing a greater level of the elicited H-reflex.


2000 ◽  
Vol 279 (2) ◽  
pp. R394-R403 ◽  
Author(s):  
A. M. Degtyarenko ◽  
M. P. Kaufman

In decerebrate paralyzed cats, we examined the effects of two central motor commands (fictive locomotion and scratching) on the discharge of dorsal horn neurons receiving input from group III and IV tibial nerve afferents. We recorded the impulse activity of 74 dorsal horn neurons, each of which received group III input from the tibial nerve. Electrical stimulation of the mesencephalic locomotor region (MLR), which evoked fictive static contraction or fictive locomotion, inhibited the discharge of 44 of the 64 dorsal horn neurons tested. The mean depth from the dorsal surface of the spinal cord of the 44 neurons whose discharge was inhibited by MLR stimulation was 1.77 ± 0.04 mm. Fictive scratching, evoked by topical application of bicuculline to the cervical spinal cord and irritation of the ear, inhibited the discharge of 22 of the 29 dorsal horn neurons tested. Fourteen of the twenty-two neurons whose discharge was inhibited by fictive scratching were found to be inhibited by MLR stimulation as well. The mean depth from the dorsal surface of the cord of the 22 neurons whose discharge was inhibited by fictive scratching was 1.77 ± 0.06 mm. Stimulation of the MLR or the elicitation of fictive scratching had no effect on the activity of 22 dorsal horn neurons receiving input from group III and IV tibial nerve afferents. The mean depth from the dorsal surface of the cord was 1.17 ± 0.07 mm, a value that was significantly ( P < 0.05) less than that for the neurons whose discharge was inhibited by either MLR stimulation or fictive scratching. We conclude that centrally evoked motor commands can inhibit the discharge of dorsal horn neurons receiving thin fiber input from the periphery.


2012 ◽  
Vol 108 (10) ◽  
pp. 2668-2678 ◽  
Author(s):  
Yu Wang ◽  
Yi Chen ◽  
Lu Chen ◽  
Jonathan R. Wolpaw ◽  
Xiang Yang Chen

The cortex gradually modifies the spinal cord during development, throughout later life, and in response to trauma or disease. The mechanisms of this essential function are not well understood. In this study, weak electrical stimulation of rat sensorimotor cortex increased the soleus H-reflex, increased the numbers and sizes of GABAergic spinal interneurons and GABAergic terminals on soleus motoneurons, and decreased GABAA and GABAB receptor labeling in these motoneurons. Several months after the stimulation ended the interneuron and terminal increases had disappeared, but the H-reflex increase and the receptor decreases remained. The changes in GABAergic terminals and GABAB receptors accurately predicted the changes in H-reflex size. The results reveal a new long-term dimension to cortical-spinal interactions and raise new therapeutic possibilities.


1994 ◽  
Vol 72 (5) ◽  
pp. 2090-2104 ◽  
Author(s):  
J. Fung ◽  
H. Barbeau

1. The modulation of the soleus H-reflex by a conditioning cutaneomuscular stimulation was investigated in 10 normal and 10 spastic paretic subjects who suffered from incomplete spinal cord lesions. The different motor tasks examined were standing, locomotion, and the maintenance of static limb postures to mimic critical gait events. The test soleus H-reflex was obtained by stimulating the tibial nerve in the popliteal fossa with a single 1-ms pulse at an intensity that produced a barely detectable M wave. The conditioning stimulus, consisting of an 11-ms train of three 1-ms pulses at 200 Hz, was delivered to the ipsilateral medial plantar arch, stimulating predominantly the medial plantar nerve, at an innocuous intensity of 2.5–3.0 X sensory threshold and at a conditioning-test delay of 45 ms. 2. During quiet standing, the H-reflex amplitude was inhibited only marginally by the conditioning cutaneomuscular stimulation, not reaching statistical significance in either the normal or spastic group of subjects. Although there was a trend of reflex inhibition in the normal subjects as the conditioning intensity was increased, a reversed trend of reflex facilitation was observed in the spastic patients. 3. During treadmill walking, the conditioned H-reflex was inhibited significantly during all phases in all the normal subjects and in one mildly impaired patient. In the moderately and severely impaired patients, cutaneomuscular stimulation selectively inhibited the soleus H-reflex in the early stance and swing phases, thereby producing a near normal phasic modulation pattern. Such modulatory effects were not present under static gait-mimicking conditions. 4. The task-specific and phase-dependent effects of cutaneomuscular stimulation on the soleus H-reflex in the spinal cord-injured patients revealed strong inhibitory influence on Ia afferents from cutaneomuscular inputs. It is plausible that inhibition occurs at both pre- and postsynaptic levels. 5. It is concluded that normal Ia modulatory mechanisms during locomotion are deficient in spastic spinal cord-injured patients and can partially and artificially be restored by cutaneomuscular stimulation applied to the sole of the foot. This can be used as a functional electrical stimulation (FES) regime in gait rehabilitation.


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