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PubMed2005

Formation of locomotor patterns in decerebrate cats in conditions of epidural stimulation of the spinal cord.

Acute experiments on decerebrate cats were performed to study the mechanism of formation of the locomotor pattern in conditions of epidural stimulation of the spinal cord. These studies showed that only segments L3-L5 contributed to generating the stepping pattern in the hindlimbs. At the optimum frequency (5-10 Hz) of stimulation of these segments, formation of electromyographic burst activity in the flexor muscles was mainly due to polysynaptic reflex responses with latencies of 80-110 msec. In the extensor muscles, this process involved the interaction of a monosynaptic reflex and polysynaptic activity. In epidural stimulation, the stepping pattern was specified by spinal structures, while peripheral feedback had modulatory influences.

Animals↗

PubMed1989

The effects of intrathecal galanin and C-fiber stimulation on the flexor reflex in the rat.

Galanin (GAL) was applied intrathecally (i.t.) at the lumbar level in decerebrate, spinalized, unanesthetized rats. GAL had no effect on the amplitude of the monosynaptic reflex over a wide concentration range, but at low concentrations if briefly facilitated the flexor reflex and at higher concentrations the facilitation was sometimes followed by a depression. GAL decreased the facilitatory effect of a conditioning stimulus train to C-fibers in the sural nerve. The depressive effect of GAL could be prevented by the i.t. coadministration of calcitonin gene-related peptide (CGRP), but not substance P (SP) and was not reversed by i.t. naloxone or bicuculline. The results illustrate the complex effect of GAL on the spinal cord, possibly exhibiting a biphasic effect. The observed effects on the flexor reflex are probably not due to changes in the excitability of motoneurons. Descending inhibitory pathways or local inhibitory non-GAL interneurons probably are not involved in the depressive effect of GAL. The possibility that the observed effects are related to primary sensory afferents containing not only GAL but also CGRP, and/or to local GAL neurons in the dorsal horn is discussed.

Animals↗

PubMed2004

Soleus H-reflex recruitment is not altered in persons with chronic spinal cord injury.

OBJECTIVE: To determine whether spasticity in persons with spinal cord injury (SCI) is associated with elevated monosynaptic reflex excitability. DESIGN: One-way experimental. SETTING: Research laboratory. PARTICIPANTS: Convenience sample of 9 subjects (8 men, 1 woman) with chronic and complete SCI and 20 persons (14 men, 6 women) with no neurologic impairment. Subjects with SCI exhibited lower-extremity spasticity as indicated by velocity-dependent increased resistance to passive muscle stretch, abnormally brisk deep tendon reflexes, involuntary lower-extremity flexion and/or extension spasms, and clonus. INTERVENTION: Soleus H-reflex recruitment curves were elicited in all subjects. MAIN OUTCOME MEASURES: Soleus H-reflex threshold (HTH), gain (HGN), and amplitude (HPP). RESULTS: There was no difference between subjects with and without SCI in HTH, HGN, or HPP. CONCLUSIONS: Spasticity in people with chronic and complete SCI was not associated with increased excitability of the connections between Ia afferent projections and motoneurons. Factors extrinsic to these connections may have a role in spasticity caused by SCI.

Adult↗

PubMed1991

Kappa-opioid receptor-mediated thermonociceptive mechanisms in streptozotocin diabetes.

The effects of the benzomorphan kappa-opiate antagonist MR 2266 and its dextro enantiomer MR 2267 were assessed on thermonociception in male Swiss Webster mice. Experimental diabetes was induced by injecting streptozotocin (200 mg/kg IP, 7-8 days before). Animals with dextrose treatment (5 g/kg, IP, at the time of opiate injection) were used as acute hyperglycemic controls. Nociception was assessed by supraspinal nociceptive reflex (licking and jumping in hot plate test) indicative of higher cognitive process as well as a predominantly lower spinal monosynaptic reflex (tail immersion test). In normoglycemic, acute hyperglycemic and diabetic mice, MR 2266 decreased, while MR 2267 increased, the reaction latencies. The results indicate tonic stereospecific kappa-opiate receptor-mediated spinal and supraspinal thermonociceptive reactions are not modulated by experimental diabetes and thus are distinct from those of naloxone-sensitive mu-opiate receptor sites.

Animals↗

PubMed1998

Electrophysiological evidence for an antinociceptive effect of ketamine in the rat spinal cord.

BACKGROUND: The dissociative anesthetic ketamine also has antinociceptive effects. The mechanism and the site of action of such effect of ketamine have been, however, elusive and controversial. The present study was conducted to examine the effect of systemically administered ketamine on spinal nociceptive transmission. METHODS: We investigated and compared the effects of ketamine (0.25-8 mg/kg) on the hamstring flexor reflex in intact, lightly anesthetized rats and spinally transected rats. The opioid receptor antagonist naloxone was used to examine the involvement of opioid receptors in the actions of ketamine. Finally, the effects of ketamine on dorsal horn neuronal activity to electrical stimulation of peripheral nerves were also studied. RESULTS: Ketamine caused similar dose-dependent depression of the hamstring flexor reflex recorded from spinally intact rats and from spinalized rats. Even the highest dose of ketamine failed to influence the monosynaptic reflex. The depressive effect of ketamine on the flexor reflex was not reversed by naloxone. Ketamine i.v. also exerted a relatively selective inhibition of the responses of dorsal horn wide-dynamic-range neurons to C-fiber input of electrical stimulation of the plantar nerve. CONCLUSIONS: Our present results support the notion that ketamine can exert a direct antinociceptive effect in rat spinal cord. Moreover, the data indicated that the spinal antinociceptive effect of ketamine does not involve naloxone-sensitive opioidergic mechanisms.

Analgesics, Non-Narcotic↗

PubMed1975

Local anesthetic activity of 1-(morpholino or piperidino)-2-propanol derivatives.

The local anesthetic activities of 1-(morpholino or piperidino)-2-propanol derivatives were investigated. These activities were observed with nerve trunk anesthesia, rabbit's corneal anesthesia and intradermal injection anesthesia. Among these propanol derivatives, No. 24 and No. 25 which possess thioether-type sulfur were the most active and the effective potency was enhanced by increasing the dissociation constant (pKa) value in a series of the compounds. Effects on cat spinal reflex were also observed. These propanol derivatives revealed no selective depression of presynaptic depression or depression of the potential of monosynaptic reflex (MSR) and polysynaptic reflex (PSR). Procaine and lidocaine had similar actions. Effects on axonal membrane potential and interaction of the calcium on these derivatives were also investigated. These derivatives decreased the action potential without altering the resting membrane potential and when antagonized with calcium, sciatic nerve action potential was decreased. Procaine and idocaine also showed the same results.

1-Propanol↗

PubMed1980

Postinhibitory rebound facilitation of the extension reflex in the high spinal cat.

Neural mechanisms of the reflex rebound of the hindlimb were studied in the high spinalized cat. After the animal had recovered from spinal shock, a light touch-pressure on the foot pad elicited a rebound extension reflex of the ipsilateral hindlimb. Excitability changes in hindlimb motor nuclei during the rebound phenomenon were examined by recording test monosynaptic reflexes (MSR). During touch-pressure stimulation, flexors such as the biceps femoris and tibialis anterior were facilitated, while extensors such as the gastrocnemius and quadriceps femoris were inhibited. After cessation of a stimulus, extensor MSRs showed a rebound facilitation which lasted for a few seconds. The greater the preceding suppression of MSR, the greater the rebound facilitation. Membrane potential changes induced in extensor motoneurons by touch-pressure were investigated by intracellular recordings. In most of the motoneurons tested (21/24), a clear membrane hyperpolarization was observed during stimulation and was followed by a rebound firing on cesstion of stimulation. Possible mechanisms underlying the rebound extension reflex were discussed.

Animals↗

PubMed1979

[Change in the feedback inhibition of monosynaptic spinal cord reflexes following removal of the anterior lobe of the cerebellum in cats].

In acute experiments on cats monosynaptic extensor and flexor reflexes and their recurrent inhibition were recorded from a L7 ventral root filament before and after removal of the anterior lobe of the cerebellum. Removal of the anterior lobe reduced the amplitude of monosynaptic extensor and flexor responses and at the same time decreased the level of recurrent inhibition of extensor reflexes and increased that of flexor reflexes. On the basis of these data it is suggested that the background control form the anterior lobe of the level of recurrent inhibition is one of the possible mechanisms participating in the cerebellar control of spinal motoneurons.

Animals↗

PubMed2006

Submaximal fatigue of the hamstrings impairs specific reflex components and knee stability.

Rupture of the anterior cruciate ligament (ACL) is one of the most serious sports-related injuries and requires long recovery time. The quadriceps and hamstring muscles are functionally important to control stability of the knee joint complex. Fatigue, however, is an important factor that may influence stabilizing control and thus cause ACL injuries. The objective of this study was therefore to assess how submaximal fatigue exercises of the hamstring muscles affect anterior tibial translation as a direct measure of knee joint stability. While 15 test participants were standing upright with the knees in 30 degrees of flexion, anterior tibial translation was induced by a force of 315 N. Two linear potentiometers placed on the tibial tuberosity and the patella recorded tibial motion relative to the femur. Reflex latencies and neuromuscular hamstring activity were determined using surface electromyography (EMG). Muscle fatigue produced a significant longer latency for the monosynaptic reflex latencies, whereas no differences in the latencies of the medium latency component were found. Fatigue significantly reduced EMG amplitudes of the short and medium latency components. These alterations were in line with significantly increased anterior tibial translation. Our results suggest that hamstring fatigue is effectively associated with mechanical loss of knee stability. This decrease in joint stability may at least in part explain higher risk of ACL injury, especially in fatigued muscles. Furthermore, we discuss why the present findings indicate that reduced motor activity rather than the extended latency of the first hamstring response is the reason for possible failure.

Adult↗

PubMedDate not supplied

Evaluation of the central nervous function in resuscitated comatose patients by multilevel evoked potentials.

Multilevel evoked potentials were examined in 17 patients who became comatose after cardiac arrest and resuscitation. In 4 patients, the P1 through N3 components of the somatosensory evoked cerebral potential (SECP) were present altogether within 100 ms after the ischemic insults. They all subsequently regained consciousness, though three of them developed intelligence and motor disturbances to some extent. In 11 patients who regained consciousness, or remained in a vegetative state, the evoked potentials which reflect brainstem functions, such as the auditory evoked brainstem potential, the R1 wave of the orbicularis oculi reflex and the slow positive wave of the somatosensory evoked brainstem potential, were recognized. The somatosensory evoked spinal potential and spinal monosynaptic reflex showed normal appearances in the state of vegetation and even after the determination of brain death. The measures of SECP could be useful in predicting restoration of consciousness.

Adult↗

PubMed2006

Up-regulation of 5-HT2 receptors is involved in the increased H-reflex amplitude after contusive spinal cord injury.

The amplitude of the H-reflex increases chronically after incomplete SCI and is associated with the development of exaggerated hindlimb reflexes. Although the mechanism for this increased H-reflex is not clear, previous studies have shown that pharmacological activation of the 5-HT2 receptors (5-HT2R) can potentiate the monosynaptic reflex. This study tested the hypothesis that increased expression of 5-HT2R on motoneurons is involved in increased H-reflex amplitude after a standardized clinically relevant contusive SCI. Adult female rats were subjected to contusion, complete surgical transection, or a T8 laminectomy only. At 4 weeks after surgery, H-reflex recordings from the hindpaw plantar muscles of contused rats showed twice the amplitude of that in laminectomy controls or transected rats. To probe the role of 5-HT2R in this increased amplitude, dose-response studies were done with the selective antagonists mianserin or LY53857 and the 5-HT2R agonist (+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI). The drugs were intrathecally infused into the lumbar cord while recording the H-reflex. Mianserin did not have any significant effects on the H-reflex after transection, consistent with the loss of distal serotonergic innervation. After contusion, both 5-HT2R antagonists reduced the H-reflex reflex amplitude with a significantly higher ID50 compared to the uninjured controls. The 5-HT2R agonist DOI significantly increased reflex amplitude in contused but not control rats. Furthermore, while 5-HT immunoreactivity was similar, contused rats displayed increased 5-HT2AR immunoreactivity in plantar muscle motoneurons compared to uninjured controls. We conclude that increased expression of 5-HT2R is likely to be involved in the enhanced H-reflex that develops after contusive SCI.

Amphetamines↗

PubMed2001

Parallel nociceptive reflex pathways with negative and positive feedback functions to foot extensors in the cat.

1. Nociceptive reflex pathways to foot extensors were investigated with particular attention given to those not following a flexor reflex (FRA) or withdrawal pattern. 2. In anaemically decapitated, high spinal paralysed cats nociceptive afferents of the foot pad were activated by noxious radiant heat (48-60 degrees C), while for comparison non-nociceptive afferents were activated by weak mechanical stimulation of the skin or graded electrical nerve stimulation. The reflex action of the afferents on hindlimb motoneurones, innervating plantaris and intrinsic foot extensors (tibial nerve), was investigated by intracellular recording, by monosynaptic reflex testing and by recording of neurograms during fictive locomotion. A possible descending control of the nociceptive and non-nociceptive pathways was tested by application of opioidergic and monoaminergic compounds. 3. Beside the typical FRA pattern evoked in the majority of hindlimb motoneurone pools by nociceptive afferents from different skin areas of the foot, the results revealed parallel excitatory and inhibitory nociceptive reflex pathways from the central pad and partly from the toe pads to foot extensors. The excitatory pathways, which did not follow the FRA pattern, were predominantly to plantaris and intrinsic foot extensors. They were distinctly less depressed by opioids and monoaminergic compounds than FRA pathways. 4. While the nociceptive FRA pathways have a general nocifensive withdrawal function, the nociceptive excitatory non-FRA pathway to the foot extensors causes a movement of the affected area towards the stimulus or at least a resistance against the stimulus, i.e. it mediates a positive feedback.

Analgesics↗

PubMed1994

Effects of TA-0910, an orally active TRH analog, on the spinal reflex in spinal rats.

Effects of TA-0910 (1-methyl-(S)-4,5-dihydroorotyl-L-histidyl-L-prolinamide), a new thyrotropin releasing hormone (TRH) analog, on spinal reflex potentials and flexor reflexes were compared with those of TRH in C1-spinal rats. Intravenously administered TA-0910 and TRH produced dose-dependent increases in the amplitudes of mono- and polysynaptic reflex potentials and withdrawal flexor reflexes. TA-0910 was more potent and more long-lasting than TRH. The stimulating actions of TA-0910 and TRH on the monosynaptic reflex potential were not antagonized by pretreatment with atropine, cyproheptadine, haloperidol or prazosin, suggesting no involvement of the cholinergic, serotonergic, dopaminergic or noradrenergic system. Intraduodenally administered TA-0910 also produced a lasting potentiation of the withdrawal flexor reflex, but intraduodenally administered TRH showed no effect. These results suggest that TA-0910 may be a more useful drug than TRH for spinal functional disorders.

Administration, Oral↗

PubMed1985

Concussive head injury producing suppression of sensory transmission within the lumbar spinal cord in cats.

This study examines the effects of concussive levels of a fluid-percussion head injury on sensory transmission within the lumbar spinal cord of the cat. Primary afferent depolarization (PAD) was suppressed for 2 to 5 minutes following injury, as assessed by dorsal root potentials and augmentation of antidromic dorsal root potentials, both evoked by stimulation of adjacent dorsal roots. Polysynaptic reflex discharges in ventral root potentials evoked by dorsal root stimulation were also profoundly suppressed during this same period, even when spontaneous and monosynaptic reflex discharges were facilitated. Changes in PAD produced by injury were abolished by spinal cord transection, but were not affected by midpontine transection. These findings suggest that concussive head injury can produce suppression of segmental sensory transmission by neurally mediated processes involving the bulbar brain stem. Recordings of dorsal root resting potentials, antidromic dorsal root potentials, and reductions of antidromic dorsal root potentials induced by tetanic root stimulation indicated that depressed segmental sensory function produced by injury was due to suppression of postsynaptic interneuronal transmission rather than to excitability changes in primary afferent fibers. Somatosensory cortical potentials evoked by dorsal root stimulation were profoundly depressed at the same time as segmental sensory transmission was suppressed, suggesting that suppressed segmental sensory transmission may also contribute to suppression of ascending sensory transmission. It is hypothesized that transmission failure of interneuronal systems in the initial period following insult may be a general response occurring in wide areas of the central nervous system, and not restricted to areas to which mechanical stress is directly applied. This response pattern may result from indiscriminate activation of interconnected excitatory and inhibitory elements of interneuronal systems.

Animals↗

PubMed1999

Gravity-dependent modulation of Ia afferent in human.

Recent work has shown that the H-reflex excitability of the human soleus motoneurones is modulated in reduced gravity and accompanied by a corresponding change in electromyographic (EMG) activity during space flight mission or different gravitational load. Spinal reflexes are often viewed as stereotyped motor patterns with limited scope for modification. However, recent evidence suggests that even short-latency, largely monosynaptic reflexes show a high degree of modulation during simple human motor activities such as walking and standing, and that the pattern of modulation can be specifically altered for the different functional requirements of each activity. Capady and Stein have demonstrated that H-reflex amplitude of the soleus increases progressively during the stance phase and reaches its peak amplitude late in the stance phase during walking. However, during running, the H-reflex is found to be significantly smaller than during walking, suggestion a modified spinal reflex gain for the different functional requirements of the motor behaviors. It is well documented that gravitational loads on the human body, spinal cords are much higher during standing in the water than standing in land. Little is known about the occurrence and influence of neural modulation in spinal cord during different gravitational load, which was not induced by posture but by voluntary background activity. The purpose of the present study was consequently to investigate how to effect is controlled H-reflex modulated during reduced gravity standing in a water in normal subjects.

Adult↗

PubMed1980

The effects of convulsant doses of penicillin on primary afferents, dorsal root ganglion cells, and on 'presynaptic' inhibition in the spinal cord.

Intracellular recordings were made from neurons in dorsal root ganglia (DRG) of rats, isolated in vitro. The depolarization of DRG cells caused by the application of gamma-aminobutyric acid (GABA) diminished reversibly when penicillin (0.08--2.0 mM) was added to the bathing fluid. The decrease of the input resistance of DRG cells measured during GABA perfusion was also depressed in the presence of penicillin, but no evidence of a shift of the reversal potential of the GABA-induced depolarization was found. Nor did penicillin (up to 10 mM) cause a change in the voltage-current function, in electrical excitability, in the inclination to repetitive firing, bursting discharge, or after discharge. In decapitate cat preparation the amplitude of the negative dorsal root potential (DRP or DR V) diminished by 0--50% after the i.v. administration of 0.5--1.0 X 10(6) I.U./kg (the convulsant dose) of penicillin. Post-tetanic depression of the DRP was aggravated by penicillin. The degree of depression of the DRP bore no relationship to the promptness of the eruption, and to the intensity, of the seizure activity induced by penicillin. The rates of rise and fall of the negative DRP (DR V) were consistently slowed, the positive DRP (DR VI) reduced, and the dorsal root reflex (DRR) blocked by penicillin. Inhibitory reflex effects presumed to be presynaptic were either enhanced or unchanged, never depressed by penicillin. This was seen when inhibitory function was gauged by monosynaptic reflex amplitude, and also from the inhibition of ventral root electrotonic excitatory postsynaptic potentials (VP EPSPs). Possible explanations of these seemingly paradoxical findings are discussed, with arguments in favor and against each.

Afferent Pathways↗

PubMed1988

Myoclonus in a patient with spinal cord transection. Possible involvement of the spinal stepping generator.

A patient with clinically complete cervical spinal cord transection developed rhythmic myoclonic movements of the trunk and lower limbs, demonstrating that, in man, such movements can be generated within the spinal cord itself when deprived of supraspinal control. Electromyographic (EMG) recordings used to define the features of the myoclonus, which had a frequency of 0.3-0.6 Hz, was bilaterally symmetric, and involved extensor muscles. The EMG bursts always appeared in phase in all muscles involved. Peripheral stimulation of flexor reflex afferents (FRA) could induce, slow or interrupt the rhythmic activity. When FRA stimulation induced a flexion reflex, it occurred between extensor EMG bursts and induced alternating flexion-extension activity which could be sustained for several cycles. Soleus and quadriceps monosynaptic reflexes were depressed during the silent period of the rhythmic activity. Several arguments, mainly the great sensitivity of the myoclonus to flexor reflex afferent stimulation, suggest that the myoclonus observed in this patient was due to partial release of a spinal stepping generator.

Adult↗

PubMed1979

Development of spinal reflexes in the rat fetus studied in vitro.

1. The onset and development of spinal reflex activity was investigated using the isolated spinal cord of the rat fetus. The potential changes generated in motoneurones were recorded extracellularly from L3 ventral roots. 2. A spike potential was recorded from the ventral root at embryonic day 13.5 in response to stimulation of the cord surface close to the ventral root. The discharge persisted in Ca2+-free solution but was blocked by tetrodotoxin. 3. At embryonic day 14.5, trans-synaptically evoked discharges were detected in motoneurones. 4. Stimulation of the dorsal root was first effective in eliciting reflex discharges at embryonic day 15.5. The reflex response then consisted of a prolonged depolarization upon which were superimposed small spikes, and was probably polysynaptic. 5. A spike potential, presumably a monosynaptic reflex, was generated at the end of fetal life. This discharge appeared first at embryonic day 17.5 in a primitive form. 6. Between embryonic day 16.5 and 17.5, stimulation of the dorsal root of diffferent segments (L1-L6) elicited responses similar to those induced by the corresponding (i.e. L3) dorsal root stimulation. These inter-segmentally induced responses were then reduced in size toward the birth. However, in the presence of strychnine, a train of spike discharges of similar shape to the segmentally induced response was also evoked by stimulation of the dorsal root at L4 or L5. These spikes disappeared during further post-natal development. 7. It is concluded that synapses in the segmental polysynaptic pathway become functional in a retrograde sequence with respect to the direction of normal reflex impulse flow. The reflex responses, elicited by stimulation of the dorsal roots of different segments, are suggested to be suppressed first by the development of inhibitory mechanisms and then by neuronal cell death or by elimination of the synapses responsible for generating the inter-segmental reflexes.

Action Potentials↗