PubMed Health⌕ Search

Biomedical subjects

R F Schmidt

Publications and source records attributed to R F Schmidt.

At least 73 records · Page 4Linked to original sources

Ultrastructural three-dimensional reconstruction of group III and group IV sensory nerve endings ("free nerve endings") in the knee joint capsule of the cat: evidence for multiple receptive sites.

The noncorpuscular endings ("free nerve endings") of thinly myelinated group III and nonmyelinated group IV afferent nerve fibers have been examined in the knee joint capsule of sympathectomized cats by transmission electron microscopy and three-dimensional reconstruction of series of semi- and ultrathin sections. The sensory ending is the most distal part of a group III or IV nerve fiber that consists only of the sensory axon and associated Schwann cells but lacks a myelin sheath and is not surrounded by perineurium. The sensory axon divides into several branches and forms a terminal tree. The branches run either as single fibers or within small Remak bundles in parallel to sensory axons of other endings; they spread along vessel walls and also extend into dense connective tissue. Each sensory axon consists of a series of spindle-shaped thick segments ("beads") connected by waist-like thin segments. Thus all axons of sensory endings have a string-of-beads appearance, which resembles that of efferent sympathetic nerve fibers. The beads of the sensory axon and the end bulb at its tip show the same ultrastructural features which are characteristic of receptive sites: an accumulation of mitochondria and glycogen particles and various vesicles in the axoplasm and "bare" areas of axolemma that are not covered by Schwann cell processes. Group III and group IV sensory endings differ in the length of their branches (up to 200 microM in group III vs. more than 300 microM in group IV), number of beads per 100 microM axon length (about seven vs. nine or ten), mean diameter of axons (0.9-1.5 microM vs. 0.3-0.6 microM), and the presence of a neurofilament core consisting of bundles of parallel microfilaments only in group III. In conclusion, we propose that the sensory part of noncorpuscular "free nerve endings" is formed by the entire terminal tree of group III or group IV nerve fibers and that the beads in the course of the sensory axon represent multiple receptive sites.

Animals↗

Gating of tactile input from the hand. I. Effects of finger movement.

Intraneural microstimulation within the median nerve of alert healthy subjects was used to evoke tactile sensations at threshold for conscious detection. The effect of movement on these sensations was studied by asking the subjects to estimate their magnitude before, during and after movement of the appropriate finger at different speeds. It was found that sensations of flutter and pressure were both attenuated by movement, as was the magnitude of spontaneous paraesthesiae. The degree of sensory inhibition correlated positively with speed of movement and was comparable to the previously reported reduction in cortical somatosensory evoked potentials by movement, using suprathreshold stimuli. These results indicate that (i) movement inhibits tactile sensations of different qualities, (ii) such inhibition is velocity-dependent, and (iii) threshold sensations are amenable to central modulation short of their abolition. It is likely that the mechanisms of inhibition of exteroceptive inputs during movement are contingent upon the character of the sensory stimulus and the nature of the motor task.

Adult↗

Gating of tactile input from the hand. II. Effects of remote movements and anaesthesia.

Tactile sensations of flutter or pressure were evoked in alert human subjects by intraneural microstimulation in the median nerve. Ratings were obtained of the magnitude of sensations at threshold for conscious detection during movement of the finger to which they were projected, of neighbouring fingers or of the opposite hand. Results showed that inhibition of flutter sensation was maximal in the moved finger (48%), with a weaker graded effect from adjacent (23%) to distant (19%) fingers of the same hand. Sensations of pressure were more markedly suppressed but the gradients were similar. Movement of the opposite hand and isometric contraction of the forearm muscles had little effect. Local anaesthetic blocks of the median and other upper limb nerves counteracted most of the inhibitory effect of movement on cutaneous flutter sensation. We conclude that sensory gating is largely restricted to the moved digits, that it applies to submodalities of both flutter and pressure and that sensory gating is mostly mediated by cutaneous receptor input from the hand.

Anesthesia↗

Changes in extracellular potassium concentration in cat spinal cord in response to innocuous and noxious stimulation of legs with healthy and inflamed knee joints.

In 20 cats anaesthetized with alpha-chloralose and spinalized at the thoracolumbar junction we investigated the role of stimulation induced accumulation of extracellular potassium in the spinal cord in the processing of nociceptive discharges from the knee joint. For that we electrically stimulated the posterior articular nerve of the knee. We further performed innocuous and noxious stimulation of the knee and of other parts of the leg and studied the effect of an acute inflammation of the knee on [K+]0 in the spinal cord. Innocuous stimulation of the skin (brushing or touching) and innocuous movements in the knee joint all induced rises in [K+]0 which were maximal at recording depths of 1500 to 2200 microns below the surface of the cord dorsum. Peak increases were 0.4 mM for touching the leg and 1.7 mM during rhythmic flexion/extension of the knee joint. Noxious stimulation of the skin, the paw, the tendon and noxious movements of the knee joint also produced rises in [K+]0, which were somewhat larger for the individual types of stimuli than those produced by innocuous intensities. Electrical stimulation of the posterior articular nerve induced rises in [K+]0 by up to 0.6 mM. Stimulus intensities sufficient to activate unmyelinated group IV fibers were only slightly effective in raising [K+]0 above the levels reached during stimulation of myelinated group II and III fibers. During development of an acute inflammation of the knee joint (induced by kaolin and carrageenan), increases in [K+]0 and associated field potentials became larger by about 25%. We assume that this reflects an increase in neuronal responses. In conclusion, changes in [K+]0 in the spinal cord are somewhat larger during noxious stimulation than during innocuous stimulation. The absolute level reached depended more on the site and type of stimulation than on the actual stimulus intensity itself. Hence a critical role of spinal K+ accumulation for nociception is unlikely.

Animals↗

Multiunit neural responses to strong finger pulp vibration. I. Relationship to age.

The effect of age on mechanoreceptive function in the distal part of the fingers was studied in 12 healthy subjects aged 18-64 years. A recording microelectrode was inserted into a sensory fascicle of the median nerve at the wrist. Multiunit mechanoreceptor activity was recorded from the fascicular field, which is typically restricted to the ulnar or radial half of one finger, corresponding to the innervation zone of one digital nerve. Strong standardized vibration (40 Hz) was applied to the finger pulp, with the amplitude of the vibration pulses high enough to induce maximal neural impulse volleys. With the same microelectrode recording position, maximal neural impulse volleys were also induced by electrical pulses applied to the ventral digital nerve supplying the finger pulp. In each subject, the areas of the mechanically and the electrically induced responses were measured (after integration and averaging) and the ratio of mechanically to electrically induced responses (MR/ER) was determined. The MR/ER ratio decreased with increasing age of the subject. This finding was considered to indicate that it is the peripheral parts of the sensory units, involved in the mechanoelectrical transfer functions, that exhibit the most pronounced degenerative changes during the ageing process. This is in line with previous histological findings of pronounced age-related degeneration of Meissner corpuscles and other mechanoreceptive end organs in the finger pulps.

Adolescent↗

Multiunit neural responses to strong finger pulp vibration. II. Comparison with tactile sensory thresholds.

In a companion microneurographic study (Schmidt et al. 1990) maximal multiunit sensory responses to finger pulp vibration were compared with maximal responses evoked by electrical stimulation of the digital nerve. It was found that the MR/ER ratio, i.e. the ratio between the magnitudes of the responses to mechanical and electrical stimulation, decreased with increasing age. The shape of this age-related decline in the ratio corresponded well with the decrease in the number of Meissner corpuscles found in histological studies. In the present study the tactile sensory detection thresholds were measured in the same subjects that participated in the companion study and the relationship between these thresholds and the MR/ER ratios was examined. The tactile sensory detection threshold increased with age. A weak negative correlation was found between the threshold and the ratio. However, after compensation for common age-mediated effects, this negative correlation disappeared. Thus, the results indicate that measurement of tactile sensory detection thresholds and determination of MR/ER ratios may complement each other, giving an indication of different types of derangement of the mechanoreceptive system.

Adolescent↗

Sensitization of articular afferents to mechanical stimuli by bradykinin.

In 18 cats anaesthetized with alpha-chloralose, we recorded from thin myelinated and unmyelinated articular afferents of the medial articular nerve of the knee joint. Bradykinin was injected intra-arterially close to the knee, alone and in combination with prostaglandin E2 (PGE2), and changes of the responses of single afferents to movements of the knee were monitored. Bradykinin changed the mechanosensitivity in 20 of 28 afferents inducing movement sensitivity in initially unresponsive units, lowering the threshold for movements in high-threshold afferents and/or enhancing pre-existing responses to innocuous and/or noxious joint movements in low and high threshold units. Also the application of PGE2 and bradykinin within a short interval sensitized the majority of these afferents, and in about 50% of the afferents the effect of the combination was superior to those induced by the single substances. We conclude that the inflammatory mediator bradykinin is able to sensitize articular afferents for movement stimuli and that PGE2 may enhance this effect. It is suggested that in arthritis inflammatory mediators act synergistically in the initiation and stabilization of the increased mechanosensitivity of slowly conducting articular afferents.

Animals↗

Serial sectioning, electron microscopy, and three-dimensional reconstruction of fine nerve fibres and other extended objects.

Two different techniques for three-dimensional reconstructions of nerve fibres or other extended fine tissue structures were developed to study the afferent innervation of the cat's knee-joint capsule. The re-embedding technique starts with series of semithin sections for light microscopic reconstructions. In a second step, selected semithin sections can be re-embedded for ultramicrotomy to examine ultrastructural details. This method offers the possibility to investigate fine structures over a distance of several hundred micrometres without any loss of ultrastructural information. The serial section-ESI technique is based on the electron spectroscopic imaging of semithin sections. Small tissue blocks are cut into series of either semithin or alternate semi- and ultrathin sections which can be directly used for a complete ultrastructural investigation. Finally, true-to-scale three-dimensional reconstructions are performed by graphical techniques or computer-aided methods.

Afferent Pathways↗

Effects of capsaicin on articular afferents of the cat's knee joint.

This study on the effects of capsaicin on primary afferents from normal knee joints of the cat was performed to further elucidate the mechanisms of articular pain evoked by an acute arthritis and by chemical irritants. It showed that close i.a. bolus injection of capsaicin (10(-7)-10(-4) M) excites most fine articular afferents (conduction velocity less than or equal to 11.3 m/s) whereas fast units are not excited. Fine afferents with low to medium thresholds to knee joint movement are less readily excited by capsaicin than high threshold ones. The response to capsaicin is usually a rapid burst of impulses of a very short latency. This response pattern differs considerably from that seen after application of endogenous substances produced in inflammation. Thus capsaicin seems to differ in its mode of action from that of endogenous algesic substances.

Animals↗

Morphological characteristics of the innervation of the cat's knee joint.

The peripheral and central terminals of primary afferents of the cat's knee joint were studied with light- and electron microscopy (including HRP-transport methods). The majority of these afferent fibres are unmyelinated or thinly myelinated. In the periphery, they terminate in non-corpuscular endings. A dense network of branching nerve fibres surround the blood vessels to terminate at the vessel walls or in the adjacent dense collagenous tissue. Besides the terminals the fibres show preterminal bulges which are assumed to represent additional transduction sites. This implies that the whole distal fibre portion has a receptive function. The spinal projection is located in lamina I and V-VII of the dorsal horn. This location parallels that of muscular and visceral fibres, pointing to the possibility of a common projection pattern for deep somatic afferent fibres in the spinal cord of the cat.

Animals↗

Excitation and sensitization of fine articular afferents from cat's knee joint by prostaglandin E2.

1. In cats anaesthetized with alpha-chloralose extracellular recordings were made from fine afferent units belonging to the medial articular nerve of the knee joint. The excitatory and sensitizing effects on articular afferents of prostaglandin E2 (PGE2) applied intra-arterially close to the joint were examined. 2. Bolus injections of PGE2 doses of 0.03-30 micrograms excited about 60% of both the group III (conduction velocity 2.5-20 m/s) and the group IV units (conduction velocity less than 2.5 m/s). The duration and size of the responses were dose dependent consisting in most cases of low-frequency discharges which lasted up to several minutes. Excitation was found among afferents with low and high mechanosensitivity. 3. Among the group III units PGE2 sensitized 64% for their responses to movements and 50% for their responses to bradykinin (applied intra-arterially close to the joint). Sensitization did not depend on the mechanical threshold previous to chemical stimulation. Among the group IV units PGE2 sensitized only 25% for their responses to movements but 75% for their reactions to bradykinin. In group IV fibres a low mechanical threshold predisposed for sensitization to movements and a higher threshold for sensitization to bradykinin. 4. Some units were sensitized and excited, others were either sensitized or excited and some units were not affected by PGE2. We conclude that PGE2 induces in a large proportion of fine articular afferents of normal joints discharges which are similar to those induced by an experimental inflammation. Thus PGE2 may be an inflammatory mediator which has a major role in the generation of the afferent activity developing in the course of an arthritis.

Action Potentials↗

Acute inflammation of the knee joint in the cat alters responses of flexor motoneurons to leg movements.

1. This is a report of changes in reflex excitability of flexor motoneurons in response to innocuous mechanical stimuli following initiation of an acute experimental inflammation of the knee joint in the chloralose-anaesthetized cat spinalized at level T12. 2. Activity of functionally single alpha- or gamma- motoneurons, identified by ventral root stimulation, was recorded in filaments of the nerve to biceps semitendinosus before and after onset of an acute inflammation. The inflammation was evoked by injection into the knee cavity of the compounds kaolin and carrageenan. 3. Measurements were made of resting activity, responses to local pressure applied to parts of the upper or lower limb, and to flexion or extension movements at the knee joint before and after onset of the inflammation. In two experiments, one in which no inflammation was initiated, and another in which recordings were made only after the inflammation had fully developed, a survey of large numbers of neurons (44 alpha and 84 gamma) showed that under control conditions only 14% of alpha-motoneurons showed a response to mechanical stimulation compared with 41% of gamma-motoneurons. In the presence of an inflammation 41% of alpha-cells were responsive compared with 64% of gamma-cells. 4. Inflammation-induced changes in activity of motoneurons including both excitatory and inhibitory effects, took 1-2 h to fully develop. Excitatory effects included a rise in resting discharge, an increase in the response to local pressure, and an increased response to flexion and/or to extension of the knee. Inhibitory effects included falls in resting discharge and/or in the responses to leg movements. 5. For 35 cells identified as alpha-motoneurons and tested both before and after initiation of an inflammation, 20 remained unresponsive throughout the experiment, whereas 4 that had not responded during the control period began after inflammation to respond to local pressure and/or flexion/extension movements. Of 11 units that exhibited some response before inflammation, 8 showed an increase with inflammation, whereas 2 became unresponsive. 6. The inflammation had rather more dramatic effects on gamma-neurons. Many showed control responses to leg movements, and these were measurably modified by inflammation. Of 56 gamma-cells tested under control conditions, 26 were unresponsive to all stimuli, whereas 30 showed some form of response including activity during flexion and extension movements of the leg. Where responses were tested both before and after onset of an inflammation, 11 of 13 unresponsive units remained unresponsive.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

Time course of mechanosensitivity changes in articular afferents during a developing experimental arthritis.

1. In 37 cats anesthetized with alpha-chloralose recordings were made from single-afferent units of the medial articular nerve (MAN) of the right knee joint. First the mechanosensitivity of such units was characterized while the joint was in normal condition. Thereafter, keeping the afferents under continuous observation, an experimental arthritis was induced by injecting kaolin and carrageenan into the joint cavity. The effects of the developing arthritis including the time course of the changes were studied on low- and high-threshold units and on afferents that had no mechanosensitivity in the normal joint. 2. The arthritis increased the mechanosensitivity in the majority of the low-threshold units, i.e., in units that responded already in the normal joint to movements in the working range. Enhanced responses to movements were found for 12 of 16 thick myelinated group II, 10 of 10 fine myelinated group III, and 1 of 3 unmyelinated group IV afferents. The augmentation of reactions developed in most cases within the first hour after the injection of the inflammatory compounds, sometimes starting immediately after the injection. A further rise of the mechanosensitivity was observed within the following 2-4 h. In most group III units enhanced responses for movements were accompanied by an induction or increase of resting discharges. In 1 group II and 1 group IV unit spontaneous activity developed in the absence of any change of movement-sensitivity. 3. The inflammation led to enhanced mechanosensitivity in high-threshold afferents, i.e., in units that responded in the normal joint only to noxious movements exceeding the working range of the knee. One group II, 10 of 12 group III, and 5 of 10 group IV units of this type became responsive to movements in the working range during development of arthritis, in most cases within the second to third hour after induction of inflammation with a further increase later on. In a high proportion of these units resting activity was induced too. Few high-threshold units developed spontaneous discharges but no responses to movements in the working range. The time course for development of resting activity was similar to that for lowering of the mechanical threshold. 4. The experimental arthritis induced afferent activity in 1 of 2 group III and 10 of 14 group IV units that in the normal joint were unresponsive to local mechanical stimulation and to innocuous/noxious movements (but responsive to a bolus of a KCl-solution applied intraarterially close to the joint).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Fiber size distribution of myelinated and unmyelinated axons in the medial and posterior articular nerves of the cat's knee joint.

The distribution of fiber size in the posterior articular nerve (PAN) and medial articular nerve (MAN) of the cat's knee joint was studied by light and electron microscopy. The myelinated fibers of the PAN ranged from approximately 1 to 18 micron, with maxima at 3-4 micron and 8-9 micron. According to the classification of Boyd and Davey (1968), the PAN contained about 34% Group III fibers, 56% Group II fibers, and 10% Group I fibers. In contrast, the MAN showed a unimodal, skewed distribution, with a range from approximately 1 to 14 micron and a maximum at 3-4 micron. According to the Boyd and Davey classification, the PAN contained about 69% Group III fibers, 30% Group II fibers, and 1% Group I fibers. Unmyelinated fibers examined in the MAN showed a unimodal distribution, with a range of from 0.1 to 1.5 micron and a maximum at 0.4-0.5 micron. To differentiate between afferent and sympathetic fibers, a sympathectomy or ganglionectomy was performed on one side. The fiber size distribution indicated a considerable overlap in the diameter of the afferent and sympathetic unmyelinated fibers. Most sympathetic fibers had a diameter of between 0.8 and 0.9 micron, whereas afferent fibers showed a maximum at 0.3-0.4 micron. When data were combined for myelinated and unmyelinated fibers in the PAN, about 74% of the afferent fibers were found to belong to Groups III and IV; they are thought to terminate in noncorpuscular endings. The other 26% were found to belong to Groups I and II; they terminate in corpuscular receptors and muscle spindle primary and secondary endings.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Opiates inhibit the discharges of fine afferent units from inflamed knee joint of the cat.

The spontaneous discharges in 15 out of 19 small-diameter afferent units from inflamed knee joints of anaesthetized cats were significantly inhibited by one or several opiates (morphine in the dose range 1.0-5.0 mg/kg; gly-ol 0.5-5.0 mg/kg; U50488 1.0-10.0 mg/kg; ethylketocyclazacine 0.5-4.0 mg/kg administered by close arterial injection into the joint). In the majority of cases a subsequent injection of naloxone (1 mg/kg i.a.) significantly reversed this effect. These data provide an electrophysiological demonstration that opiates may act on opiate receptors located at peripheral sites of primary afferent fibres and hence exert a peripheral 'analgesic' effect.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Convergent inputs from articular, cutaneous and muscle receptors onto ascending tract cells in the cat spinal cord.

Responses were recorded from 160 ascending tract cells in segments L4 to L6 of the spinal cord in chloralose anaesthetized, spinalized cats. The tract cells were identified by antidromic activation following stimulation of pathways in the lateral and ventral funiculi at the level of the spinal cord transection at the thoracolumbar junction. Axonal conduction velocities ranged from 9 to 114 m/s. A sample of 152 of the neurones examined could be subdivided according to the distribution of their receptive fields into 49 cells activated just from receptors located in skin ("s" cells), 17 neurones excited by receptors in deep tissues ("d" cells), 15 units with a convergent input from receptors in skin and deep tissues ("sd" cells), and 25 neurones with a convergent input from the knee joint and either skin ("sj" cells), deep tissues ("dj" cells) or both ("sdj" cells). No receptive fields could be demonstrated for the remaining 46 neurones. "S" and "sj" cells were found almost exclusively in the dorsal horn, whereas many "d", "sd", "sdj" and "dj" units were in the ventral horn. Almost all of the cells that lacked receptive fields were in the ventral horn or intermediate grey. Ninety-one of 158 cells (56%) demonstrated no background activity. Of these, 43 cells (27%) lacked receptive fields. Many of the silent neurones were in the ventral horn, but some were in the dorsal horn. Of 25 cells having knee joint input, 18 (72%) had background activity. All of the neurones that had a receptive field in the knee joint also had a convergent input from receptors in other tissues. In 3 cases, there was a receptive field in the skin over the foot ("sj" cells). For 16 cells, receptive fields included not only the knee joint but also skin and deep tissue ("sdj" cells). Usually, the cutaneous receptive field was near the knee joint, but sometimes it was remote, such as on the foot. The deep receptive fields were chiefly in the muscles of the thigh and/or leg. For 6 "dj" cells, the receptive fields included not only the knee joint but also deep fields like those of "sdj" cells. Cutaneous receptive fields were classified as "low threshold" (cells excited best by innocuous intensities of mechanical stimulation), "wide dynamic range" (cells activated by weak mechanical stimuli, but the best responses were to noxious stimuli) or high threshold (innocuous stimuli had little effect, but noxious mechanical stimuli produced a vigorous discharge).(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗