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[Excitable actions of counterirritants on cutaneous sensation].

Studies were conducted on the actions of counterirritants on sensory receptors in the skin and spinal monosynaptic reflex. Nerve discharges in the cat's saphenous nerve were promoted by the external application of menthol and nonylic vanillyl amide ( NVA ) dissolved in ethanol on the receptive field. When plasters containing counterirritants were externally applied on the receptive field, marked activation was recognized in touch-pressure-pin prick fibers immediately after the application as seen with plaster without drugs, but significantly high activity was maintained thereafter, and the increased firing rate in touch-pressure-pin prick-cold fibers lasted for 60 min. The activity of pressure-pin prick fibers was increased with the lapse of time and warm fibers was not influenced. Effects on activities of spinal dorsal horn cells were almost similar to the changes in activities of primary afferent from the skin. Monosynaptic reflex elicited by stimulation on the medial gastrocnemius nerve was weekly inhibited (significantly different from control at P less than 0.05), by the external application of plasters, and motoneuron receiving IPSP from the skin lightly touched on was observed. These findings suggest that the receptors activated with counterirritants were thought to be as follows: A delta and C polymodal nociceptors, A delta and C cold nociceptors, and slow adapting cutaneous mechanoreceptors. The cutaneous mechanoreceptors were also activated by the application of plasters. The volley from sensory nerve excited with counterirritants was thought to cause a suppression on the spinal monosynaptic reflex resulting from an inhibition on the motoneuron.

Administration, Topical↗

[Effect of rhythmic stimulation of the locus coeruleus on segmental reflex reactions evoked by stimulation of cutaneous and muscle afferents].

Conditioning stimulation of the high-threshold cutaneous afferents exerted in decerebrated and anesthetized cats combined facilitatory and inhibitory actions on the extensor monosynaptic reflex, while stimulation of high-threshold muscle afferents exerted only an inhibitory one. Inhibition of the extensor monosynaptic reflex diminished substantially during rhythmic stimulation of locus coeruleus. Facilitation of the flexor monosynaptic reflex after volleys of high-threshold cutaneous and muscle afferents did not undergo any changes under such stimulation.

Animals↗

[Suppression of the dorsal root potentials of the cat spinal cord by manganese and cobalt ions].

In anesthetized spinal cats, perfusion of lumbosacral spinal cord with artificial CSF containing manganese (1.5-3.0 Mm/l) or cobalt (6.0 mM/l) ions, led to reversible suppression of negative dorsal root potentials (DRP), induced by stimulation of ipsilateral hindlimbs' afferent nerves. The depression of the DRP proceeded in connection with the depression of presynaptic inhibition of extensor monosynaptic reflexes induced with impulse volleys in the group I flexor muscle afferents. The depression of inhibition was not associated with changes in amplitudes of testing monosynaptic reflexes. The DRP is concluded to have a synaptic origin.

Animals↗

Excitability changes of ankle extensor group Ia and Ib fibers during fictive locomotion in the cat.

The present study examines the modulation of gastrocnemius-soleus (GS) monosynaptic reflexes as well as the intraspinal threshold changes of GS group I primary afferent terminals ending in the intermediate and motor nuclei during fictive locomotion in high decerebrate cats. The amplitude of the monosynaptic reflexes (MSR's) evoked in the medial gastrocnemius by stimulation of the lateral gastrocnemius nerve was increased during the extensor (E) phase, decreased during the flexion (F) phase of the step cycle and remained transiently increased after spontaneous episodes of fictive stepping. The intraspinal threshold of populations and of single group Ia GS afferent fibers ending in the motor pool, as well as of single Ia and Ib fibers ending in the intermediate nucleus, showed a sustained reduction during the episodes of fictive locomotion with superimposed cyclic changes in phase with the step cycle. During fictive walking and trotting the reduction of the intraspinal threshold of both Ia and Ib fiber terminals was maximal during the middle or late portion of the F-phase. During fictive gallop elicited by stimulation of the superficial peroneus nerve, the decrease in the intraspinal threshold of the Ia afferent fibers occurred however in phase with the activity of the GS motoneurons. During episodes of fictive locomotion slow, sustained negative DC potential shifts lasting tents of seconds, reflecting an increase in the extracellular potassium concentration were recorded at the base of the dorsal horn and in the intermediate nucleus. The present findings support the existence of tonic and phasic depolarization of the intraspinal terminals of GS group Ia and Ib primary afferents during spontaneous fictive locomotion. It is suggested that accumulation of potassium ions in the extracellular space contributes mainly to the sustained depolarization of group I fibers. The phasic depolarization would be mostly due to the activation of specific sets of interneurons and may, in the case of Ia fibers, contribute to the cyclic modulation of the MRS elicited during fictive locomotion.

Afferent Pathways↗

Facilitation and inhibition of synaptic transmission in the spinal cord: an electroneurographic study in humans.

The neurographic activity evoked either by stimulation of the tibial nerve at the popliteal fossa or by percussion of the Achilles tendon has been recorded at lumbar and thigh levels, in order to find out whether conduction time, temporal dispersion and central delay of the neural volleys underlying the monosynaptic reflex (H or T) may change as a function of stimulus intensity; under facilitatory or inhibitory experimental conditions; "spontaneously", i.e. during the steady state. The reflexly evoked ventral root discharge (VRD) decreases in latency with increasing stimulus intensity up to the maximum reflex response in the absence of changes in afferent (thigh to spine) or efferent (spine to thigh) conduction times. Reduction of the central delay was greater with mechanical than electrical stimulation, probably due to the combined effect of spatial and temporal summation under the former experimental condition. The latency of the VRD related to the maximal H response was not further modified by supramaximal stimulus strengths. The Jendrassik manoeuvre caused a significant decrease in latency of the VRD, the opposite effect being observed during calf muscle vibration. A significant relationship between amplitude and latency of single VRDs could be demonstrated during the "steady state". Our data point to the existence of a positive correlation between the size of the motoneuronal pool activated by an afferent volley and speed of transmission in the reflex pathway, both during the "steady state" and under either facilitatory or inhibitory experimental conditions, provided that the test stimulus strength does not exceed the maximum reflex response (H or T). No detectable signs of peripheral dispersion of the VRD could be demonstrated, irrespective of the stimulus employed: this suggests that the axon diameters of the motoneurones contributing to the monosynaptic reflex fall within a fairly narrow distribution.

Adolescent↗

Long-lasting facilitation of a monosynaptic pathway as a result of "partial" axotomy of its presynaptic elements.

We investigated the long-lasting effects of severing an axonal branch on the function of the synapses made by the remaining branches of the "partially" transected axon. The experimental model used was the monosynaptic reflex pathway of the cat lumbar cord. Preliminary surgical procedures consisted of a dorsal column (DC) hemisection at the L3--L4 level on the left side under aseptic conditions. During the final recording experiments, the monosynaptic reflex (MSR) of the operated and normal (control) side was studied in motorpools in the L7 and S1 segments. The results indicate that the DC operation produced on the operated side (a) an enhancement of the MSR and (b) a more powerful postetanic potentiation, both of the "early" and "late" varieties. These effects were seen as early as 34 days and as late as 121 days after the original DC hemisection. Control experiments were carried out to exclude denervation supersensitivity, supraspinal effects, and normal asymmetries between sides as the mechanism underlying these effects. A presynaptic change in the operated axons, resulting in an increased synaptic efficiency, is proposed as the possible mechanism.

Animals↗

Cortical projection of afferent information from tendon organs in the cat.

In cats anaesthetized with chloralose, evidence has been sought for the projection of information from tendon organs to the sensory receiving areas of the cerebral cortex. Selective stimulation of afferent fibres from tendon organs has been achieved by raising the threshold to electrical stimulation of the fibres from primary endings of muscle spindles. The method uses longitudinal vibration at 200-250 Hz to elicit, over a period of 20 min, one impulse for each excursion of the vibrator from all of the spindles in the test muscle, soleus or medial gastrocnemius. The accumulated post-spike positivities following passage of the impulses are thought to be responsible for the rise in threshold. Segmental monosynaptic reflex testing after a bout of vibration was used to confirm that the residual Group I volley no longer contained impulses from muscle spindles. The volley in response to stimulating the nerve of the test muscle was timed to facilitate the monosynaptic reflex of a synergist. Before vibration 5- to 10-fold facilitation of reflex amplitude could be produced; however, after vibration, if all the spindle primary endings had been effectively engaged by the stimulus, no detectable facilitation remained. This test was found to be sensitive and reproducible. An afferent volley containing only activity of tendon organ afferents evoked small-amplitude potentials from the post-sigmoid gyrus of the contralateral pericruciate cortex. The field was highly localized and lay caudal to the main receiving area for activity from the sural nerve and from afferents of hip flexor muscles. Recordings with tungsten micro-electrodes revealed that the surface-evoked activity took origin in cellular discharges in the internal pyramidal layer of area 3a. Recent psychophysical experiments have provided evidence for a sense of muscle tension, as distinct from a sense of effort, and the tendon organ has been suggested as the likely receptor of origin. Our electrophysiological observations now provide a firm experimental basis for such a proposal.

Animals↗

Evidence that inhibition of a nociceptive flexion reflex by stimulation in the rostroventromedial medulla in rats occurs at a premotoneuronal level.

The amplitude of the hamstring monosynaptic reflex was measured before and during stimulation of the rostroventromedial medulla (RVM) in the lightly anaesthetized rat. The RVM was stimulated at currents sufficient to completely inhibit a paw withdrawal reflex evoked by noxious heat. At these currents, RVM stimulation produced no significant change in monosynaptic reflex amplitude, evidence that inhibition occurs at a premotoneuronal level.

Anesthesia↗

Effects of thyrotropin-releasing hormone on phencyclidine- and ketamine-induced spinal depression in neonatal rats.

The effects of thyrotropin-releasing hormone (TRH) were examined on the monosynaptic reflex and on the activity of motoneurons in the spinal cord of the neonatal rat to elucidate the mechanism of action of TRH and its ability to reverse the spinal depression caused by phencyclidine and ketamine. Phencyclidine (2-32 microM) and ketamine (25-200 microM) produced a concentration-dependent depression of the monosynaptic reflex with a 50% inhibitory concentration (IC50) of 8.4 and 77.5 microM, respectively. This depression, however, was significantly attenuated by simultaneous application of TRH (0.03-1 microM) in a concentration-dependent manner. The dose-response curves for phencylidine and ketamine were shifted to the right in the presence of TRH (0.1 microM) with an increase in the respective IC50 of 2- to 3-fold. The incidence of generation of motoneuron spikes, elicited by dorsal root stimulation, was significantly increased by TRH in each neuron tested, concomitantly with an increase in the spontaneous firing rate. These results suggest that TRH directly excites alpha-motoneurons to reverse the spinal depression produced by phencylidine and ketamine.

Animals↗

Ethanol and spinal presynaptic inhibition in man.

Ethanol, 0.65 gm per kilogram of body weight, was administered orally to 6 normal subjects. The mean blood ethanol levels ranged from 0.74 to 0.99 gm per liter over a subsequent 40-minute testing period. The proportion of the soleus motoneuron pool activated by the Achilles tendon reflex was reduced. Vibratory inhibition of the monosynaptic reflex was used as an estimate of spinal presynaptic inhibition. It was unaffected by ethanol.

Adult↗

Trigeminal mesencephalic neurons innervating functionally identified muscle spindles and involved in the monosynaptic stretch reflex of the lateral pterygoid muscle of the guinea pig.

Location of the neurons in the trigeminal mesencephalic nucleus innervating stretch receptors of the lateral pterygoid muscle and the mode of their synaptic connection on the lateral pterygoid motoneurons of the guinea pig were studied physiologically as well as morphologically, in comparison with the trigeminal mesencephalic neurons innervating muscle spindles in the superficial masseter muscle, with the following results: stimulation of the caudal half of the trigeminal mesencephalic nucleus evoked monosynaptic excitatory postsynaptic potentials in the ipsilateral lateral pterygoid motoneurons. Stimulation of the lateral pterygoid nerve directly evoked spike potentials in the neurons located in the caudal half of the ipsilateral trigeminal mesencephalic nucleus, which responded with increased firing to stretch, and with silent period to twitch, of the ipsilateral lateral pterygoid muscle. Averaging of intracellular potentials of the lateral pterygoid motoneurons with extracellular spike potentials of these trigeminal mesencephalic neurons revealed excitatory postsynaptic potentials after a monosynaptic latency, but no inhibitory postsynaptic potentials. Injection of horseradish peroxidase into the lateral pterygoid muscle labeled 15-20 cells in the caudal half of the ipsilateral trigeminal mesencephalic nucleus, while 174-228 cells retrogradely labeled by horseradish peroxidase were found throughout the whole rostrocaudal extent of the ipsilateral trigeminal mesencephalic nucleus following injection of horseradish peroxidase into the masseter muscle. It was concluded that neurons in the caudal half of the trigeminal mesencephalic nucleus send their peripheral processes to stretch receptors, presumably muscle spindles, in the ipsilateral lateral pterygoid muscle and that their central processes have excitatory synapses on ipsilateral lateral pterygoid motoneurons, thus comprising the afferent limb of a monosynaptic stretch reflex arc of the lateral pterygoid muscle of the guinea pig.

Animals↗

Alteration in rate modulation of reflexes to lumbar motoneurons after midthoracic spinal cord injury in the rat. I. Contusion injury.

This study investigated the regulation of reflex excitability in normal and midthoracic contusion-injured animals. Recent observations revealed that rate depression, a rate-modulatory process that decreases reflex excitability, was significantly decreased following experimental midthoracic contusion injury. The present experiments were performed to extend those studies and to determine if posttetanic potentiation (PTP), a rate-modulatory process that increases reflex excitability, also was altered in lumbar monosynaptic reflexes (MSRs) following midthoracic contusion injury. In normal animals, a mean PTP of 160% of the pretetanus control was observed at 30 sec following tetanus of the tibial MSR. The decay of the PTP in normal animals followed a rapid initial, then a more gradual pattern, before returning to pretetanus values by 5 min posttetanus. Following midthoracic contusion injury, the maximal (unpotentiated) MSRs were significantly increased in amplitude, whereas the percent potentiation of the PTP of the tibial MSRs was significantly decreased. PTP decay in postcontusion animals was significantly more gradual than observed in normal animals and followed a single decay process. Further analysis of rate depression of tibial MSRs in normal animals revealed that the attenuation pattern produced by stimulation within the lower range of test frequencies was different from that produced by stimulation at the higher test frequencies. Following contusion, rate depression of tibial MSRs was significantly reduced at all test frequencies. These physiological changes in the stretch reflex neural pathway are discussed relative to the development of spasticity.

Animals↗

Medullary control of lumbar motoneurons during carbachol-induced motor inhibition.

The present study examined the effects of stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) on the Ia-monosynaptic reflex and the membrane potential of lumbar motoneurons. Stimulation of the NRGc was carried out in acute decerebrate cats during motor suppression induced by the intrapontine microinjection of carbachol. During carbachol-induced motor suppression, compared with control conditions (prior to the administration of carbachol), NRGc stimulation resulted in a statistically significant reduction in the Ia-monosynaptic reflex. This effect was maximal at an interval of 45 ms following NRGc stimulation. NRGc stimulation also induced, in lumbar motoneurons, a large amplitude (3.17 mV +/- 0.36 [S.E.M.]), long duration (54.73 ms +/- 3.52 [S.E.M.]) inhibitory postsynaptic potential whose peak coincided with the interval of maximum reflex suppression. These results suggest that carbachol activates pontine neurons that excite cells of the medullary NRGc. We believe that these medullary neurons, in addition to those of the nucleus pontis oralis (NPO)7, participate in the modulation of the descending inhibitory pathway that is responsible for the phenomenon of response-reversal and generalized atonia during naturally occurring active (i.e. REM) sleep.

Animals↗

Is the Mmax/Hmax ratio a reliable index of the monosynaptic excitability in man? Recruitment curves for H- and M-responses using monopolar and bipolar recording techniques.

The amplitude changes of M- and H-potentials, recorded monopolarly and bipolarly from different leading-off areas on the surface of m. triceps surae upon varying the stimulus intensity from threshold to supramaximal values, in a state of rest and fixed muscle length, are investigated. It is shown that: a) the Mmax/Hmax amplitude ratio cannot serve as a reliable index for a quantitative evaluation of the monosynaptic reflex excitability of the motoneurone pool and b) recording along the medial line of m. soleus in the region from 1.5 to 8.0 cm under the distal insertion of the two gastrocnemii into the Achilles tendon in a state of rest and submaximal values of the stimulus intensity, both mono- and bipolar recording techniques can equivalently be used in studying the changes in the monosynaptic reflex excitability.

Electric Stimulation↗

Isoflurane and an alpha 2-adrenoceptor agonist suppress nociceptive neurotransmission in neonatal rat spinal cord.

Analgesia is an important component of general anesthesia. alpha 2-adrenoceptor agonists such as clonidine and dexmedetomidine are effective analgesics at the spinal level, and furthermore, they reduce the volatile anesthetic requirement. In order to probe a possible spinal-level contribution to general anesthetic-induced analgesia, the effects of dexmedetomidine were tested in an isolated spinal cord preparation. The effects of dexmedetomidine were compared with those of isoflurane, and dexmedetomidine-isoflurane interactions were explored. The test response was a nociceptive-related slow ventral root potential (slow VRP) recorded from the isolated neonatal rat spinal cord in response to electrical stimulation of a dorsal root. At 0.2-1.28 vol%, isoflurane reversibly depressed the slow VRP. At a lower concentration (0.14 vol%), isoflurane increased the slow VRP in three of five preparations. At 1.0-1.28 vol%, isoflurane also depressed the monosynaptic reflex. Recovery on washout usually was to a level greater than control. The N-methyl-D-aspartate (NMDA) receptor antagonist (DL)-2-amino 5-phosphonovalerate (10 microM) prevented the rebound to levels above control on isoflurane washout. The earlier components of the slow VRP were more sensitive to isoflurane than were the later. Dexmedetomidine (0.5-10 nM) depressed the slow VRP and had no effect on the monosynaptic reflex. The slow VRP depends on both substance P and glutamate NMDA-receptor-mediated neurotransmission; isoflurance and dexmedetomidine depressed responses to both substance P and NMDA. Although the two agents depress responses to the same neurotransmitters, there is no evidence that they act at the same cellular site(s). There was no significant interaction between dexmedetomidine and isoflurane. The results suggest that isoflurane exerts marked inhibitory effects on spinal neurotransmission, depressing both substance P and glutamate-mediated pathways. There is a possible biphasic effect on the NMDA receptor. To the extent that nociception depends on these neurotransmitters, isoflurane may be expected to exert profound analgesic effects at the spinal level. By blocking responses to strongly arousing stimuli, these effects may contribute to general anesthesia. Suppression of nociceptive neurotransmission at the spinal level may contribute to dexmedetomidine's anesthetic-sparing properties as well as to analgesia by this agent.

Adrenergic alpha-Agonists↗

Glucocorticoid effects on serotonergic and noradrenergic facilitation of spinal monosynaptic transmission.

The ability of an intensive glucocorticoid regimen (i.e., triamcinolone diacetate, 8 mg/kg i.m./7 days) to modify the lumbar spinal monosynaptic reflex response to serotonergic and noradrenergic agents has been examined in unanesthetized acute spinal (C-1 sectioned) cats. Triamcinolone pretreatment enhances the 2N facilitatory actions of amitriptyline (AMIT), 5 mg/kg i.v., when given after D,L-5-hydroxytryptophan (5--HTP), 50 mg/kg i.v., as compared to untreated control preparations. Subsequent administration of methysergide, a serotonin receptor blocking drug, in a dose of 1 mg/kgh i.v. promptly and completely reverses the monosynaptic response increase by AMIT in untreated animals, but not in the glucocorticoid treated ones. In contrast, the monosynaptic facilitation normally produced in untreated preparations by methoxmine (MX), 1 mg/kg i.v., a centrally active noradrenergic agonist, is prevented as a result of triamcinolone dosing. These results demonstrate a glucocorticoid effect on spinal biogenic amine function such that serotonergic monosynaptic reflex activation is enhanced while noradrenergic reflex stimulation is depressed. Furthermore, they suggest that the elevations in plasma cortisol in certain cases of psychiatraic depression may; contribute to alterations in central biogenic amine synaptic activity.

5-Hydroxytryptophan↗

Spinal motor preparation in humans.

This study examined the influence of preparatory 'set' on the modulation of monosynaptic reflex excitability immediately prior to the initiation of a voluntary movement. Six subjects performed 3 tasks which varied the level of preparatory set according to the availability of temporal and event anticipation. A choice reaction-time task restricted both temporal and event anticipation; a simple reaction-time task restricted temporal anticipation while allowing event anticipation; and a coincidence-timing task permitted both temporal and event anticipation. The response for all tasks performed was ankle plantarflexion. The excitability of the monosynaptic reflex was examined by eliciting H reflexes to the right soleus muscle at 50 msec intervals over the final 400 msec preceding the initiation of voluntary muscle contraction. All 3 tasks showed an initial depression and later increase in the H reflex amplitude. The onset of reflex facilitation was the same for the choice and simple reaction-time tasks, commencing 74 msec prior to voluntary muscle contraction. However, the coincidence-timing task showed an earlier onset of reflex facilitation. Reflex facilitation preceded voluntary muscle contraction by 130-337 msec during the performance of this task. Thus, it appears that the modulation of monosynaptic reflex excitability is not time-locked to the onset of voluntary muscle contraction, but rather is controlled by the preparatory set of the subject. The modulation of reflex excitability represents a separate, though necessary, stage in the organization and initiation of voluntary movement.

Adult↗

Comparison of soleus H reflex facilitation at the onset of soleus contractions produced voluntarily and during the stance phase of human gait.

Variations in the soleus monosynaptic reflex have been studied in normal human subjects during soleus contractions while walking, and compared with those observed during voluntary soleus activation. The monosynaptic reflex was always more facilitated during voluntary contractions than during walking. The EMG activity was identical in both situations. Under the assumption that this reflects an identical excitability of the motoneuronal pool, this different soleus H-reflex facilitation can be attributed to a difference in the excitatory efficiency of the group I volley evoked by the H-reflex stimulation. It is suggested that the level of presynaptic inhibition exerted on Ia fibers could be lower during walking than during voluntary contraction.

Ankle↗