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S Mense

Publications and source records attributed to S Mense.

At least 73 records · Page 4Linked to original sources

Response properties and descending control of rat dorsal horn neurons with deep receptive fields.

The study was designed to obtain information on the spinal processing of input from receptors in deep somatic tissues (muscle, tendon, joint). In anaesthetized rats, the impulse activity of single dorsal horn cells was recorded extracellularly. In a pilot series, the proportion of neurons responding to mechanical stimulation of deep tissues was determined: 46.7% had receptive fields in the skin only, 35.5% could only be driven from deep tissues (deep cells), and 17.7% possessed a convergent input from both skin and deep tissues (cutaneous-deep cells). In each category, neurons with low and high mechanical thresholds were encountered. Experiments employing a reversible cold block of the spinal cord showed that deep cells with high threshold were subject to a stronger descending inhibition than low-threshold deep cells. In cutaneous-deep neurons the input combination high-threshold cutaneous and high-threshold deep was the most frequent one (48.7% of the cutaneous-deep cells). In these presumably nociceptive cells the descending inhibition had a differential action in that the input from deep tissues was more strongly affected than was the cutaneous input to the same neuron. The recording sites of the neurons with deep input were located in the superficial dorsal horn and in and around lamina V. The results suggest that in the rat a considerable proportion of dorsal horn cells receives input from deep nociceptors and that this input is controlled by descending pathways in a rather selective way.

Animals↗

Response behaviour of cat dorsal horn neurones receiving input from skeletal muscle and other deep somatic tissues.

1. In chloralose-anaesthetized cats, lumbosacral dorsal horn neurones driven by receptors in skeletal muscle and other deep tissues (tendon, joint, bone) were studied. 2. Upon mechanical stimulation two main types of neurones were found: units having exclusive input from deep tissues (D cells, 28.8%) and units with input from both cutaneous (C) and deep (D) receptors (C-D cells, 71.2%). In both categories, low-threshold mechanosensitive (LTM) and high-threshold mechanosensitive (HTM) elements were present. 3. Neurones responding exclusively to noxious stimulation of skeletal muscle were not found; the input from muscle nociceptors converged on the dorsal horn cells together with other deep or cutaneous input. D cells with exclusively HTM input were numerous; these could from the anatomical basis for a specific spinal pathway for deep pain. 4. For C-D neurones with input from deep nociceptors the cutaneous receptive field (RF) was usually located distal to the deep one. This arrangement might be of relevance for the occurrence of hyperaesthetic skin distal to painful deep lesions. 5. Cold block of the spinal cord resulted in a marked increase in the neurones' mechanical responsiveness and in the number of RFs per neurone. Simultaneously, the proportion of HTM RFs increased, particularly in cells with input from skeletal muscle. 6. The recording sites in the dorsal horn were located in the superficial dorsal horn and in and around laminae V/VI. Evidence is presented that in dorsal horn cells with deep input not only the mechanical excitability but also the degree of convergence is controlled by descending spinal pathways.

Animals↗

Long-term changes in discharge behaviour of cat dorsal horn neurones following noxious stimulation of deep tissues.

Certain pathological types of afferent input are supposed to lead to long-term changes in the responsiveness of dorsal horn neurones. This mechanism might be of importance for the development of neurological disturbances such as chronic pain. The present study was undertaken in order to find out whether dorsal horn neurones--particularly those processing input from deep tissues--exhibit long-lasting changes in response behaviour after a short-lasting noxious stimulation of deep tissue. In anaesthetized cats, the impulse activity of single dorsal horn cells was recorded extracellularly with glass microelectrodes. In a small number of cells that had multiple receptive fields (RFs), the algesic agent bradykinin was injected into a muscle RF and the properties of all RFs retested at regular time intervals. Following noxious chemical stimulation of one RF, the injected and the other RFs of the same neurone often showed changes which consisted of an increase in size, a lowering of mechanical threshold and appearance of new RFs. In an attempt to assess the influence of a single noxious stimulus on the entire population of dorsal horn cells, the properties of a greater sample of neurones were compared before and after injection of bradykinin into the deep tissues of the hind limb. Every cell encountered was classified as being driven by (1) cutaneous receptors only, (2) deep receptors only, (3) both input sources, or (4) electrical stimulation only (cell without receptive field). Following injection of bradykinin, the proportion of cells with both deep and cutaneous input and of those having background activity rose, and the percentage of cells without a receptive field decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Termination patterns of identified group II and III afferent fibres from deep tissues in the spinal cord of the cat.

In chloralose-anaesthetized cats, the impulse activity of single afferent fibres supplying receptors in the deep tissues of the hindlimb (fasciae, muscles, ligaments, joint capsules) was recorded using micropipettes filled with a solution of horseradish peroxidase. Only myelinated fibres with conduction velocities up to 40 m/s (Group III and Group II units) were studied, i.e. fast conducting afferent fibres from muscle spindles and tendon organs were excluded. The fibres were functionally characterized with the use of mechanical stimuli such as local pressure and joint movements. The results show that a relationship exists between the functional properties of a given afferent unit and the location of its terminals in the spinal cord. Since the conduction velocity and hence the diameter of the fibres was similar in all the units studied, these factors appear not to be of importance for determining the pattern of spinal termination. Out of 84 units, 42 were classified as high-threshold mechanosensitive, 26 as low-threshold mechanosensitive, and 16 as secondary endings from muscle spindles. Following physiological identification the fibres were ionophoretically injected with horseradish peroxidase and their trajectory in the white and gray matter of the spinal cord visualized histologically with diaminobenzidine. High-threshold mechanosensitive units took a lateral course in the posterior funiculus and usually did not bifurcate. They exhibited two different patterns of spinal termination, one being characterized by terminal arborizations in both lamina I and deeper laminae (mostly IV/V), the other one by an exclusive projection to lamina I. Low-threshold mechanosensitive units often showed a bifurcation in the posterior funiculus and did not have a uniform termination pattern. The main areas of termination were lamina II and laminae IV-VI. The slowly conducting secondary endings from muscle spindles projected mainly to laminae VI and VII with additional collaterals entering the ventral horn. They thus had a termination pattern similar to that reported for fast conducting afferent fibres (above 50 m/s) from muscle spindle secondary endings. With the exception of one high-threshold mechanosensitive unit none of the stained fibres possessed terminal arborization and boutons in lamina III. It is concluded that different types of Group II and III primary afferent fibres from deep tissues exhibit different patterns of spinal termination.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Histological and neurophysiological changes induced by carrageenan in skeletal muscle of cat and rat.

Infiltration of the rat gastrocnemius-soleus (GS) muscle with carrageenan induced a myositis which was characterized histologically by an accumulation of polymorphonuclear leukocytes around capillaries and small arterioles. In chloralose-anaesthetized cats having an inflamed GS-muscle, the discharge behaviour of single muscle receptors with group III and IV afferent fibres was recorded. Concerning background activity, only group III receptors showed a significant increase, whereas a significant lowering in mechanical threshold was present only among group IV receptors. Both high- and low-threshold mechanosensitive receptors showed signs of a sensitization. In contrast to group IV receptors in the cat, rat group IV receptors showed a significantly higher level of background activity in inflamed muscle but no increased responsiveness to mechanical stimuli. Acetylsalicylic acid (ASA) influenced only some of the receptors in the inflamed tissue. Leukotriene D4 did not act as a sensitizing substance but depressed the activity of group IV muscle receptors.

Animals↗

Spinal and supraspinal terminations of primary afferent fibers from the gastrocnemius-soleus muscle in the cat.

The central distribution of the terminations of primary afferent fibers from the gastrocnemius-soleus muscle in the cat was examined with the method of transganglionic transport of horseradish peroxidase. At the segmental level, the main projection areas were found to be laminae I and V-VII; in the rostrocaudal direction, the terminations extended from the third sacral segment to nucleus Z. A 40% solution of horseradish peroxidase in 2% dimethylsulfoxide was applied to the central cut ends of the muscle nerves in an open pool for several hours and subsequently was removed. A capsule of tracer solution applied during the survival period of the animals was found to result in additional labeling due to peripheral leakage. The tissue sections were processed with tetramethylbenzidine. Termination fields were consistently observed ipsilaterally in: lamina I from the L4 through S3 segments, being most dense in L6 and S1; lateral lamina V in L6 and S1-3; medial laminae VI-VII from L5 through S3; medial Clarke's column from L1 through L4; the ventral aspect of the gracile nucleus; and, nucleus Z. Little or no labeling was found in laminae II-IV in experiments in which peripheral leakage of tracer solution was prevented. The distribution of reaction product in laminae VI-VII and Clarke's column corresponds to the projections of large-diameter afferent fibers from the gastrocnemius-soleus muscle. The projections to laminae I and V, which are attributed to small-diameter sensory fibers, indicate involvement of these laminae in sensory modalities mediated by slowly conducting muscle afferent fibers, e.g. deep nociception. This pattern contrasts strongly with the central projections of cutaneous fibers, which terminate heavily in laminae II-IV, but resembles the central distribution of fibers from tooth pulp and viscera.

Afferent Pathways↗

Bradykinin-induced modulation of the response behaviour of different types of feline group III and IV muscle receptors.

1. In order to test the hypothesis that bradykinin has a sensitizing action on muscle receptors (e.g. during a myositis), the response properties of single group III and IV afferent units from the cat gastrocnemius-soleus muscle were compared before and after infiltration of their receptive fields with a bradykinin solution. According to their responses to graded natural stimuli (local pressure, stretch, contractions and temperature changes) the units were classified as (a) nociceptors, (b) low-threshold pressure-sensitive (LTP) receptors, (c) contraction-sensitive (CS) receptors and (d) thermosensitive receptors. 2. Bradykinin activated the majority of both the nociceptive and low-threshold (LTP, CS and thermosensitive) receptors but a sensitization was prominent only among the nociceptors. Most of the sensitized nociceptors showed increased responses to mechanical, but not to thermal, stimuli. The sensitization appeared to be quite specific in that the nociceptors were sensitized either towards local pressure stimulation or to active contractions, but never towards both forms of stimulation. 3. Both group III and group IV nociceptors were sensitized by bradykinin, the proportion of sensitized receptors being greater for group III units. 4. Some of the low-threshold receptors (particularly the CS units) showed a desensitization under the influence of bradykinin. 5. Although bradykinin (by lowering the mechanical thresholds of nociceptors into the innocuous range) could produce the symptom of allodynia, it was not capable of eliciting all the changes in receptor behaviour which are known to occur in inflamed tissues. For instance, no ongoing activity of longer duration and no substantial sensitization of low-threshold receptors have been observed in the present study.

Animals↗

Effects of a carrageenan-induced myositis on the discharge properties of group III and IV muscle receptors in the cat.

1. To see how muscle group III and IV receptors are affected by a myositis, the background activity and mechanical excitability of slowly conducting afferent units from normal and inflamed muscles were studied in chloralose-anesthetized cats. The inflammation was induced by infiltrating the gastrocnemius-soleus muscle with a suspension of 2% carrageenan. According to their responsiveness to local pressure stimulation the receptors were classified as touch units, moderate pressure units, and noxious pressure (probably nociceptive) units. The impulse activity in single afferent units was recorded up to 14 h after induction of the inflammation. 2. In inflamed muscle both group III and group IV receptors showed an increase in the proportion of units having a background activity and in the mean background activity. The differences reached statistically significant levels in group III fibers only. 3. A characteristic feature of the background activity of some receptors in inflamed muscle was its intermittent nature: the discharges occurred either as grouped impulses of short duration or as phases of relatively high discharge frequency alternating with long periods of silence. 4. In normal muscle no receptor exhibited intermittent discharges or had a discharge rate exceeding 7 imp/min. Thus the presence of an intermittent background activity or a high frequency of the background discharge can be considered as characteristic for afferent units from an inflamed muscle. 5. The time course of the background activity showed two peaks, one occurring 2-4 h, the other one 6-7 h after induction of the inflammation. Recordings of single units during the transition from the normal to the inflamed state demonstrated that the first increase in background discharge took place 1-1.5 h after injection of carrageenan. 6. The proportion of noxious pressure units was reduced and that of moderate pressure units increased in inflamed muscle. In this case the difference was significant for group IV units only. 7. The response curves upon mechanical stimulation did not show significant differences in normal and inflamed muscle, i.e., sensitized noxious pressure units behaved similar to real touch units or moderate pressure units with respect to their mechanical excitability. 8. No apparent correlation existed between the receptors' mechanical threshold and degree of background activity in inflamed muscle. This suggests that the inflammation-induced change in mechanical excitability and development of background activity are independent phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Observations on the morphology of axons and somata of slowly conducting dorsal root ganglion cells in the cat.

In anaesthetized cats, the somata of cervical dorsal root ganglion (DRG) cells were impaled with glass micropipettes containing horseradish peroxidase. Slowly conducting afferent units were first classified by the conduction velocity of the peripheral axon (group IV: less than 2.5 m/s, group III: 2.5-30 m/s) and then injected iontophoretically with horseradish peroxidase in order to visualize the perikaryon and the axons close to the ganglion. All units classified as group IV had non-myelinated peripheral and central axons. DRG cells classified as group III were morphologically heterogeneous. Units conducting in the lower group III range had non-myelinated axons on both sides of the bifurcation; in those having an intermediate conduction velocity only the peripheral axon was myelinated, and in the fastest conducting group III units both the peripheral and central axons were myelinated. One out of the 36 stained cells gave rise to 3 processes, namely 1 central axon and 2 peripheral branches. The latter ones left the ganglion at its distal pole. Within the ganglion a significant tapering of the peripheral axon of group IV afferent units was observed. In the frequency distribution histogram of cell sizes, the cross-sectional areas of group IV somata were not restricted to the lower extreme of the distribution, but showed a great overlap with the somata of group III and even group II and I units.

Animals↗

Non-myelinated afferent fibres do not originate exclusively from the smallest dorsal root ganglion cells in the cat.

In chloralose-anaesthetized cats, the somata of cervical dorsal root ganglion cells with non-myelinated peripheral branches (group IV units) were impaled with glass micropipettes containing a 10% solution of horseradish peroxidase (HRP). The units were identified by their conduction velocity in the peripheral nerve (less than 2.5 m/s). After identification, HRP was injected iontophoretically into the soma. No significant correlation was found between the conduction velocity and cross-sectional areas of these somata. The soma sizes were distributed over a great portion of the whole size spectrum of the cells in the ganglia studied (C7 and C8).

Animals↗

Spinal termination of nociceptive afferent fibres from deep tissues in the cat.

In anaesthetized cats, the impulse activity in afferent fibres from the deep tissues of the lower hindlimb was recorded at the dorsal root entry zone with micropipettes filled with horseradish peroxidase solution. After identification of the fibres as nociceptive with the use of mechanical stimuli and ascertainment of the deep location of the receptive field (in fascia, muscle, tendon, ligament or joint capsule) the enzyme was injected iontophoretically into the axon. Histochemical processing of the tissue with diaminobenzidine was employed to visualize the spinal terminal arborizations of the units. The fibres conducted at 18.3-40.0 m/s; they showed two different patterns of termination: (1) units terminating exclusively in lamina I of the dorsal horn; (2) units possessing their main projection area in laminae IV/V with only a few collaterals and boutons in lamina I. Thus, the nociceptive fibres from deep tissues terminated in those laminae of the dorsal horn which are known to contain cells of origin of ascending nociceptive tracts.

Afferent Pathways↗

Different types of slowly conducting afferent units in cat skeletal muscle and tendon.

In chloralose-anaesthetized cats, the impulse activity of single afferent units conducting at less than 30 m s-1 and having receptive fields in the triceps surae muscle or the calcaneal tendon, was recorded from thin filaments of the dorsal roots L7 and S1. The receptive fields of the units were tested with a variety of graded natural stimuli (local pressure, stretch, contractions, temperature changes). In addition, the algesic agent bradykinin was injected into the receptive fields, but the sensitivity of the receptors to this substance was not used for classification purposes. Four types of receptors could be distinguished using the strongest response to innocuous natural stimulation as the criterion for characterizing a given ending: (a) nociceptors showing no response to innocuous forms of stimulation and requiring noxious (tissue-threatening) stimuli to be clearly activated; (b) low-threshold pressure-sensitive receptors responding to innocuous indentation of the tissue but being relatively insensitive to stretch and contractions; (c) contraction-sensitive receptors reaching high discharge frequencies during active contractions of moderate force and innocuous stretch, but being relatively insensitive to local pressure stimulation; (d) thermosensitive receptors responding strongly to small changes in temperature without reacting to innocuous mechanical stimulation. The possible involvement of the different receptor types in central nervous functions (nociception, mechanoreception, ergoreception, thermoregulation) is discussed.

Animals↗

Basic neurobiologic mechanisms of pain and analgesia.

Information about tissue damaging, subjectively painful stimuli is transmitted to the central nervous system by specific receptors. Histologically, they are supposed to be free nerve endings connected to the spinal cord by thin myelinated (A delta or group III) and nonmyelinated (C or group IV) fibers. Nociceptive information is transferred to secondary cells mainly in the surface layers (lamina I and II) and the neck (lamina V) of the dorsal horn; it then ascends the anterolateral funiculus contralaterally in axons of the spinothalamic tract. One portion of this tract ends in the ventroposterior and posterior thalamus. It is assumed that it mediates the discriminative component of a pain sensation. The emotional-affective component of a pain sensation is supposed to be produced by that portion of the spinothalamic tract that terminates in the intralaminar nuclei and by the spinoreticular tract. The existence of a cortical pain center has not yet been proved, nor is it clear where in the cerebrum pain is consciously felt. The descending pain inhibiting systems, originating in the brain stem, may block the transfer of nociceptive information at a spinal level, probably using enkephalin as a transmitter. It is probable that they mediate morphine-induced analgesia. Lesions of tissue release endogenous substances, such as serotonin and certain prostaglandins, which sensitize receptors. The analgesic effect of nonsteroidal anti-inflammatory drugs, such as aspirin, can be explained by the inhibition of prostaglandin synthesis and the desensitization of nociceptors.

Afferent Pathways↗

The distribution of afferent fibers from the gastrocnemius-soleus muscle in the dorsal horn of the cat, as revealed by the transport of horseradish peroxidase.

The transganglionic transport of horseradish peroxidase (HRP) was used to examine the distribution of afferent fibers from the gastrocnemius-soleus (GS) muscle in the dorsal horn of the cat. Intense labeling was consistently observed in lamina I (in segments L4 to S3) and in the lateral portion of lamina V (segments L6 and S1-3), but not to any significant extent in laminae II-IV. These terminal fields were ascribed to the small-diameter (group III/IV) GS afferent fibers.

Afferent Pathways↗

Responses in muscle afferent fibres of slow conduction velocity to contractions and ischaemia in the cat.

The aim of the study was to find out to what extent muscle receptors with slowly conducting afferent fibres (group III and IV) are activated by muscular contractions of moderate force, and what kind of muscle afferents could mediate the pain of ischaemic exercise. In chloralose-anaesthetized cats, the impulse activity of single afferent units from the triceps surae muscle was recorded from dorsal root filaments during muscular contractions with intact blood supply and after occlusion of the muscle artery. Two types of responses were observed to contractions without muscular ischaemia. One was characterized by sudden onset and a graded response amplitude to contractions of increasing force. In most cases stretching the muscle was also an effective stimulus. Units showing this response behaviour were labelled c.s.m (contraction-sensitive with mechanical mechanism of activation). The other response type had a more delayed onset and often outlasted the exercise period; because of the unknown mechanism of activation, units of this kind were labelled c.s.x. The proportion of c.s.m receptors was significantly higher amongst group III than amongst group IV units. During ischaemic contractions of comparable force the c.s.m and c.s.x receptors exhibited an unchanged or a decreased response amplitude. Under these conditions another receptor type (N, for nociceptive) was activated which did not respond to contractions with intact blood supply. Vigorous activations during ischaemic work were only observed in group IV receptors. The majority of the 131 group III and IV units tested did not respond to contractions at all. These contraction-insensitive (c.i.) endings probably comprised different receptor populations (nociceptors, thermoreceptors, low-threshold mechanoreceptors). It is concluded that the various central nervous effects of muscular exercise without ischaemia which are known to be due to raised activity in thin muscle afferents (e.g. cardiopulmonary adjustments, spinal locomotor reflexes) are probably produced by the c.s.m and c.s.x types. The pain of ischaemic contractions is most likely mediated by the N receptors most of which possess non-myelinated afferent fibres.

Action Potentials↗

Neurons in ventrobasal region of cat thalamus selectively responsive to noxious mechanical stimulation.

1. A survey was made of neurons located in the ventral posterior lateral nucleus of the cat thalamus and its immediate vicinity for elements with specifically nociceptive properties. 2. Pipette microelectrodes filled with a dye solution were used to obtain extracellular recordings of unitary activity in 34 animals anesthetized with chloralose. 3. The great majority of the over 1,000 different single units responding to sciatic nerve stimulation noted in this series of experiments could also be excited by innocuous mechanical stimulation of skin or subcutaneous tissues. An infrequent but consistently noted group of units excited by A-alpha beta delta sciatic nerve volleys did not respond to innocuous mechanical manipulation or A-alpha beta sciatic nerve volleys; they were excited only by either noxious levels of mechanical stimulation or when volleys included the activity of more slowly conducting myelinated fibers. The latencies of such "high-threshold" units to sciatic volleys were longer than those of the other units. 4. Histologically identified recording sites marked by dye were recovered for 17 high-threshold units. Twelve of the 17 could be excited by noxious manipulations of restricted parts of the contralateral hindlimb. Nine of the 12 had cutaneous receptive fields, whereas 3 responded only to stimulation of subcutaneous tissues. None of the 17 high-threshold units evidenced additional discharges that could be correlated with the C-fiber component of sciatic nerve volleys. 5. The high-threshold units typically exhibited a low level of irregular background activity, which increased on repeated noxious stimulation of the peripheral receptive fields. Tactile units of the same or adjacent penetrations usually had a much greater degree of ongoing activity, often marked by bursts at a relatively high frequency. 6. The recording sites for the 17 high-threshold neurons were located dorsal and ventrolateral to the core of the ventrobasal nuclei and were not found in the midst of the low-threshold, cutaneous, mechanoreceptive population. During vertical stereotaxic penetrations, high-threshold units were noted dorsal or ventral to the location of ventrobasal tactile units in a pattern consistent with the core's somatotopic arrangement. 7. These results support the concept that the cat ventrolateral thalamus receives a small but distinct selectively nociceptive projection. The nociceptive neurons appear to be located in a shell that surrounds the main tactile projection to the ventral posterior lateral nucleus and that retains at least part of the topographic arrangement characteristic of the tactile core. Presumably, this projection is part of an organization identifying and localizing noxious stimulation.

Animals↗

Reduction of the bradykinin-induced activation of feline group III and IV muscle receptors by acetylsalicylic acid.

1. In chloralose-anaesthetized cats, the influence of systemically or locally applied acetylsalicylic acid (ASA) on the responses of thin-fibre muscle receptors to close-arterial injections of bradykinin was studied. 2. Many of the slowly conducting (group III and IV) muscle afferents had a background activity of low frequency. This discharge was either unaffected or slightly increased by the ASA doses used. In two units which had a very high discharge rate ASA led to a marked decrease in background activity. 3. On local (I.A. or I.M.) injection of ASA, doses below 1 mg were sufficient for reducing the bradykinin-induced activations of group III and IV muscle receptors. The reduction lasted for about 15-30 min. 4. On systemic (I.V.) administration of ASA (50 mg/kg body weight) the reduction in response magnitude to bradykinin became significant 8 min after injection of the analgesic. The effect was maximal about 10 min later and lasted for more than 60 min. 5. Five receptors were found which gave a repeated response to 5-hydroxytryptamine (5-HT) injected at 10 min intervals. The 5-HT-induced activations could not be reduced by ASA (50 mg/kg I.V.). 6. Most of the receptors responding to bradykinin had a high threshold on mechanical stimulation and thus were probably nociceptors. It is concluded that the reduction of their bradykinin-induced activations reflects the suppression of nociceptive information by an analgesic. Since the recordings were obtained from primary afferent units the data constitute direct evidence for a peripheral action of ASA.

Action Potentials↗