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Biomedical subjects

R F Schmidt

Publications and source records attributed to R F Schmidt.

At least 37 records · Page 2Linked to original sources
PubMed1997

Quantification of cat's articular afferents containing calcitonin gene-related peptide or substance P innervating normal and acutely inflamed knee joints.

In cats with an acute (32 h) unilateral knee joint inflammation the proportion of calcitonin gene-related peptide-(CGRP) and substance P-(SP) immunoreactive articular afferents, retrogradely labelled by Fast Blue (FB), were determined using immunohistochemistry. The proportion of neurons containing CGRP was significantly higher on the inflamed side (52%) than on the contralateral side (39%) and in controls (42%). However, the proportion of SP-immunoreactive articular perikarya on the inflamed side (26%) did not differ from the contralateral side (24%) and the control cats (22%). These data indicate that acute inflammation induces the synthesis of CGRP but not of SP in joint afferents.

Acute Disease↗
PubMed1997

Effects of the 5-HT1 receptor agonists, sumatriptan and CP 93,129, on dural arterial flow in the rat.

The blood flow in and around the medial meningeal artery (dural arterial flow) was recorded in the exposed parietal dura mater encephali of the anesthetized rat using laser Doppler flowmetry. Local electrical stimulation of the dura mater (pulses of 0.5 ms delivered at 7.5-17.5 V and 5 or 10 Hz for 30 s) caused temporary increases in dural arterial flow. The effects of the 5-HT1 receptor agonists sumatriptan and CP 93,129 on the basal flow and the electrically evoked increases in flow were examined. Topical administration of undiluted sumatriptan (12 mg/ml) lowered the basal and the evoked flow by 20% on average. Systemic (i.v.) administration of sumatriptan (0.24, 0.72 and 3.6 mumol/kg) caused a short-lasting reduction of the evoked flow increases only at the higher doses while the basal flow was not significantly altered. Systemic administration of CP 93, 129 (0.46 and 4.6 mumol/kg) caused no significant changes of the basal and the evoked flow. At a dose of 23 mumol/kg CP 93,129 lowered the basal flow by 20% and the evoked flow by 30% for 20 min. The systemic arterial pressure was not significantly altered by sumatriptan and CP 93,129 within the whole range of doses. It is suggested that sumatriptan and CP 93,129 at high doses exert inhibitory effects on those fine afferent nerve fibers which release the calcitonin gene-related peptide, since this neuropeptide mediates the evoked increases in dural arterial flow.

Animals↗
PubMed1996

Morphine microinjected into the nucleus tractus solitarius and rostral ventrolateral medullary nucleus enhances somatosympathetic A- and C- reflexes in anesthetized rats.

The modulatory effects of morphine microinjected into localized areas of the brainstem on somatosympathetic A- and C-reflexes were examined in urethane-anesthetized rats. Somatosympathetic A- and C-reflexes were elicited in a branch of the inferior cardiac nerve by electrical stimulation of myelinated (A) and unmyelinated (C) afferent fibers in the tibial nerve. Morphine (0.002-0.2 microgram/50 nl) was microinjected into the rostral, intermediate and caudal parts of the nucleus tractus solitarius (NTS), the rostral ventrolateral medullary nucleus (RVLM), the caudal ventrolateral medullary nucleus (CVLM), the locus coeruleus (LC), the raphe magnus (RM), the periaqueductal gray (PAG), and the accumbens nucleus (Acb). Microinjections of morphine (0.2 microgram) into the intermediate and caudal NTS produced significant augmentations of the A- and C-reflexes, C-reflexes being more markedly enhanced than A-reflexes. Microinjection of morphine (0.2 microgram) into the RVLM produced a prominent increase in the C-reflex, the threshold dose for a significant increase being 0.02 microgram morphine. Microinjection of morphine up to 0.2 micrograms/50 nl into the other areas mentioned above had no significant effect on either reflex component. All opiate-induced increases of the reflex discharges could be reversed by intravenous application of naloxone (2 mg/ kg). The reflex augmentation induced by microinjection of morphine into the NTS may be caused by suppressing inhibitory baroreceptor information or by enhancing excitatory chemoreceptor information in the NTS. Augmentation of the C-reflex induced by microinjection of morphine into the RVLM may be caused by facilitating C-reflex pathways or by suppressing inhibitory neural circuits involved in the C-reflex within the RVLM.

Afferent Pathways↗
PubMed1996

Parallel organization of proprioceptive inputs from joint receptors to cortical somatosensory areas I and II in the cat.

1. Studies in monkeys indicate that proprioceptive and tactile inputs are conveyed from the thalamus to the primary somatosensory cortex (SI) and thence to the secondary somatosensory area (SII) in a serial scheme. In contrast, in the cat, tactile information is conveyed in parallel from the thalamus to SI and SII. The present study, in the cat, employed reversible inactivation of SI to determine whether proprioceptive inputs to SII from joint receptors depend on an indirect serial path via SI or are conveyed over a direct path from the thalamus. 2. SI and SII foci for knee joint inputs were determined with evoked potential mapping. Reversible inactivation of the SI focus by cooling had no effect on the amplitude, latency or time course of SII potentials evoked by joint inputs. There was also no consistent effect on the response levels of individual SII neurones examined during SI inactivation. Furthermore, there was no attenuation of the later components of the responses, and therefore no evidence that these depended on an indirect path to SII via SI. 3. Results demonstrate that proprioceptive inputs project directly from thalamus to SII over a pathway organized in parallel with that to SI, in contrast to the serial scheme reported for proprioceptive processing in primates.

Animals↗
PubMed1995

Somatostatin-like immunoreactivity in primary afferents of the medial articular nerve and colocalization with substance P in the cat.

The proportion of somatostatin-containing dorsal root ganglion cells innervating the knee joint of the cat via the medial articular nerve was determined by using retrograde labeling with fast blue and immunohistochemistry. Immunoreactivity was found in 8.6% of labeled cell bodies. In colchicine-treated ganglia, the proportion increased to 16.8%. Only small and intermediate-sized perikarya showed somatostatin-like immunoreactivity, indicating that this neuropeptide is synthesized predominantly in primary afferent units with unmyelinated sensory axons but may also be present in primary afferents with thinly myelinated sensory fibers. Colchicine treatment had no influence on the cell size distribution. Colocalization of somatostatin with substance P was determined by comparing the proportions of immunopositive dorsal root ganglion cells after incubation with antibodies against substance P or somatostatin or with a mixture of both. Substance P-like immunoreactivity was found in 18.1% (untreated ganglia) and 19.6% (colchicine treated ganglia) of the labeled neurons. After incubation with a mixed antibody solution, 18.2% of joint afferents in untreated and 19.9% of the cells in colchicine-treated ganglia were immunopositive. Comparing this result with the results obtained using somatostatin and substance P antibodies alone, one can calculate that both neuropeptides are colocalized in about 17% of the cat's knee joint afferents. About 3% of the neurons contain only substance P, whereas almost none of the neurons contain only somatostatin. Based on this fact, one can assume that both neuropeptides are coreleased in peripheral tissue as well as in the central nervous system.

Afferent Pathways↗
PubMed1995

The opioid antagonist naloxone does not alter discharges of nociceptive afferents from the acutely inflamed knee joint of the cat.

Recent studies have shown peripheral antinociceptive effects of opiates in inflamed tissue. To test whether the afferent activity during an acute inflammation may also be suppressed by endogenous opioids, we studied whether the application of the opioid antagonist naloxone would alter the afferent discharges from the cat knee joint inflamed by kaolin and carrageenin. After i.a. bolus administration of naloxone (3 micrograms/kg and 1 mg/kg) close to the joint, neither the ongoing activity nor the responses to noxious and innocuous movements significantly changed in group III or group IV units. Since naloxone did not unmask opioidergic activity under these conditions, we conclude that the development of increased activity in joint afferents during an acute kaolin/carrageenin-induced inflammation is not tonically suppressed by endogenous opioids.

Afferent Pathways↗
PubMed1995

Fine sensory innervation of the knee joint capsule by group III and group IV nerve fibers in the cat.

Afferent group III and IV nerve fibers of the knee joint markedly differ in their responsiveness to mechanical stimulation, which may be reflected in the structure and location of their terminals. Therefore, in sympathectomized cats, the fine afferent innervation of the knee joint capsule was studied via ultrastructural three-dimensional reconstructions over distances of up to 300 microns. Small peripheral nerves and "free" (noncorpuscular) sensory nerve endings were found in a superficial layer of the outer fibrous part of the capsule, in the patellar retinaculum, and in the outer and inner surface layers of the medial collateral and patellar ligaments. Group III nerve fibers showed a proximal myelinated portion inside the nerve, an intermediate portion that lacks a myelin sheath and is only surrounded by perineurium, and a distal portion outside of the perineurium that forms the sensory ending proper. Group IV fibers showed only two distinct portions, an intraperineurial (proximal) and an extraperineurial (distal) portion without any further morphological differences. Outside of the perineurium, a network formed by Schwann cells ("Schwann cell reticulum") provides a pathway for the distal portion of the sensory axons. No distinct subgroups of the sensory terminal fibers could be defined according to the configuration of the Schwann cells and the nerve fiber terminals. Sensory terminals were located adjacent to different structures such as venous and lymphatic vessels, fat cells, and collagenous fibers. Distinct parts of the same terminal nerve fiber were found in close contact to a vessel wall; others were surrounded by dense collagenous tissue. Close to sensory endings, mast cells and mast cell-like cells were frequently found, indicating a functional relationship.

Animals↗
PubMed1995

Modulation of somatocardiac sympathetic reflexes mediated by opioid receptors at the spinal and brainstem level.

Modulation of somatosympathetic reflexes at the spinal cord and the brainstem was studied by administering opioid receptor agonists into the intrathecal space of the lumbar spinal cord and into the subarachnoid space of the cisterna magna in rats anesthetized with alpha-chloralose and urethane. Somatocardiac sympathetic A- and C-reflexes were elicited by electrical stimulation of myelinated (A) and unmyelinated (C) afferent fibers of the tibial nerve, respectively. Intrathecal administration of the mu-opioid receptor agonist DAMGO selectively depressed the C-reflex in a dose-dependent manner (minimum effective dose 10 ng), whereas the intrathecal injection of the delta-opioid receptor agonist DPDPE and the kappa-opioid receptor agonist U-50,488H only at doses of 10 micrograms and 100 micrograms, respectively, led to a significant depression of the C-reflex. Injection of DAMGO into the cisterna magna enhanced both A- and C-reflexes in a dose-dependent manner (minimum effective dose 1 ng). The administration of neither DPDPE nor U-50,488H into the cisterna magna affected A- or C-reflexes. It is concluded that the activation of mu-opioid receptors is mainly or exclusively responsible for suppressing somatosympathetic C-reflexes at the spinal cord and for enhancing them at the brainstem.

Adrenergic Fibers↗
PubMed1995

A new combination of methods for the localization, identification, and three-dimensional reconstruction of the sensory endings of articular afferents characterized by electrophysiology.

A combination of methods is described to identify and reconstruct corpuscular and non-corpuscular sensory endings of group II and group III nerve fibers following functional examination by electrophysiology. Afferent units activated by electrical stimulation of the medial articular nerve of the cat's knee were analyzed by single fiber recordings and characterized by their responsiveness to mechanical stimuli. The receptive fields of the units were closely demarcated by fine needles when the responses elicited by insertion of the needles were being recorded. After fixation, the tissue around the demarcated field was dissected and histologically processed. Series of semithin sections were cut from the embedded tissue blocks containing the receptive fields. Corpuscular endings of group II fibers and peripheral myelinated group III nerve fibers, presumably corresponding to the characterized units, were identified by light microscopy of semithin sections and localized within the demarcated area. Non-corpuscular endings were identified by electron microscopy of ultrathin sections cut in alternation with, or after re-embedding of, semithin sections. Morphometric analysis of ultrathin section series allowed the measurement of parameters such as the mean axon diameter and the organelle content of the sensory endings. The methods described are appropriate for collecting data that correlate the structural and functional characteristics of sensory endings in deep tissues.

Animals↗
PubMed1995

An intact nerve preparation for monitoring inputs from single joint afferent fibres.

A preparation is described that permits the monitoring of activity from individual joint afferent nerve fibres in an intact peripheral nerve of the cat. The joint nerve used was the medial articular nerve (MAN) that supplies the medial and anteromedial aspects of the knee joint. This nerve is sufficiently fine that if freed from nearby tissue over a length of 2-5 cm and placed over a platinum hook electrode it is possible to identify and monitor, from the intact nerve, the impulse activity from each group II joint afferent fibre activated by mechanical stimulation of the joint capsule. The signal-to-noise ratio exceeds 5:1 and in most cases was approximately 10:1. With this preparation it is now possible to examine the central actions and security of transmission at central synaptic targets for single, identified group II joint afferent fibres.

Afferent Pathways↗
PubMed1995

Increase of meningeal blood flow after electrical stimulation of rat dura mater encephali: mediation by calcitonin gene-related peptide.

1. The dura mater encephali of the rat was exposed and the blood flow around branches of the medial meningeal artery was monitored with a laser Doppler flowmeter. Changes in the meningeal blood flow (MBF) following electrical stimulation of the dura mater at a parasagittal site were registered. The effects of human calcitonin gene-related peptide (h-alpha CGRP) and the CGRP antagonist (h-alpha CGRP8-37) on the MBF were tested. 2. Electrical stimulation with rectangular pulses of 0.5 ms, 10-20 V, 5-10 Hz and a duration of 30 s caused an increase of the MBF in 14 out of 16 rats tested. The increases were dependent on stimulus strength and frequency. 3. The increase in MBF was inhibited in a dose-dependent manner by topical application of 0.1 ml of h-alpha CGRP8-37 at concentrations of 10(-7) - 10(-5) M. The highest dose abolished the increase in MBF. 4. Topical administration of 0.1 ml of h-alpha CGRP at a concentration of 10(-4) M increased the basal MBF by 15% on average. 5. It is suggested that the increase in MBF following electrical stimulation of the dura mater is mediated by the release of CGRP. The contribution of the dural afferent and sympathetic and parasympathetic efferent nerve fibres to this response are discussed.

Animals↗
PubMed1995

Calcitonin gene related peptide released from dural nerve fibers mediates increase of meningeal blood flow in the rat.

The parietal dura mater encephali of the rat was shown by immunohistochemistry to be densely innervated by calcitonin gene related peptide (CGRP) immunoreactive nerve fibers spreading around the medial meningeal artery and its branches. Electrical stimulation of the dural surface (10-20 V, 5-10 Hz, 10-30 min) caused a depletion of CGRP-immunopositive fibers, suggesting a release of CGRP. The dural blood flow around branches of the medial meningeal artery was also monitored with a laser Doppler flowmeter. Short periods (30 s) of electrical stimulation with parameters that presumably released CGRP form nerve fibers caused a repeatable and constant increase of the blood flow for 1-2 min. This evoked increase could dose dependently be inhibited by topical application of the CGRP antagonist hCGRP8-37. Accordingly, administration of hCGRP increased the basal blood flow. We conclude that stimulation of trigeminal afferents innervating the dura mater releases CGRP from peptidergic afferent terminals, thereby causing vasodilatation and increasing the meningeal blood flow, an important element of neurogenic inflammation.

Animals↗
PubMed1994

Responses of lateral thalamic neurons to algesic chemical stimulation of the cat knee joint.

In order to gain insight into the representation of articular pain of the knee at the supraspinal level, recordings were made from lateral thalamic neurons receiving input from afferent fibres of the knee joint in chloralose-anaesthetized cats. Dorsoventral penetrations were made through the ventral posterior lateral nucleus (VPL) using high intensity electrical stimulation of the medial articular nerve (MAN), which contains a high proportion (80%) of A delta and C afferent fibres. All recording sites were verified histologically. Close retrograde injections (300 microliters over 6 s) into geniculate artery of KCl (2 x isotonic), bradykinin (BK, 2.6 or 26 micrograms) and capsaicin (200 microM) were used to test the response properties of thalamic neurons. Of the 50 MAN-positive units tested, 20 showed a response to intra-arterial KCl; of these 20, 12 had a response to BK; 8 of these 12 units were additionally tested with capsaicin and all responded. KCl and capsaicin injections had similar mean response latencies (4.5 and 6.8 s), whereas BK had a longer mean latency (18.6 s). The mean peak response was greatest for capsaicin (168 impulses/s), then KCl (87.5 imp/s) and least with BK (36.4 imp/s). The mean response duration was longest with capsaicin (118 s), followed by BK (67.5 s) and least with KCl (27.9 s). Most of these were convergent wide dynamic range (WDR) neurons with a deep receptive field in the knee joint and hindlimb muscle and/or cutaneous distal hind limb digit, located to the dorsal or ventral periphery of the lateral division of the VPL, the VPL1. In addition, 8 neurons showed inhibitory responses to KCl and/or BK injections. The background activity of VPL1 neurons activated by saphenous nerve stimulation was inhibited by the nociceptive articular stimulus with a magnitude and time course which mirrored the excitatory responses in the periphery of VPL1. These results support the concept that the lateral thalamus plays an important role in mediating discriminative aspects of joint pain.

Afferent Pathways↗
PubMed1994

Mitochondria in fine afferent nerve fibres of the knee joint in the cat: a quantitative electron-microscopical examination.

The distribution of mitochondria, their content and concentration (expressed as the ratio of the mean volume of mitochondria and the surface of the sensory axon) were determined in group-III and -IV nerve fibres innervating the knee joint capsule in the cat. Mitochondria mainly accumulated in axonal swellings ("beads") and end bulbs of the terminal branches. Between single nerve fibres, marked differences in the content and the concentration of mitochondria were obtained in proximal portions (inside of the perineurium) and in distal portions (unmyelinated sensory endings). In group-III nerve fibres, the mitochondrial concentration ranged from 0.005 to 0.030 microns 3/microns 2 (proximal portion) and from 0.016 to 0.080 microns 3/microns 2 (distal portion). In unmyelinated group-IV nerve fibres, the values also showed a broad variation ranging from 0.001 to 0.011 microns 3/microns 2 (proximal portion) and from 0.003 to 0.019 microns 3/microns 2 (distal portion). The wide range of mitochondrial concentrations may reflect different energy consumption during receptive processes: nerve fibres with a low mechanical threshold and a high probability of excitatory events may be rich in mitochondria, whereas fibres with a high mechanical threshold and a low probability of excitatory events may be poor in mitochondria.

Animals↗
PubMed1994

Electrophysiological evidence for a spinal antinociceptive action of dipyrone.

Electrophysiological experiments in anesthetized cats and rats were performed in order to study the effects of dipyrone on single afferent fibers from the knee joint and on spinal cord neurons with knee joint input. The neurons were activated and/or rendered hyperexcitable by an acute inflammation in the knee joint. In the joint nerve in cats, intravenous dipyrone (25-100 mg/kg) reduced ongoing activity in 10/12 thinly myelinated afferents but only in 1/10 unmyelinated afferents; the responses to movements of the inflamed knee were reduced in 8/10 thinly myelinated but only in 3/10 unmyelinated units. The reduction of activity was significant 20-30 min after application and was maximal at 60-180 min. In the spinal cord of spinalized cats, intravenous dipyrone (25-100 mg/kg) reduced ongoing activity and/or responses to pressure onto the inflamed knee in 14/16 neurons and in non-spinalized rats similar effects were seen in 10/11 neurons. Effects on spinal cord neurons started 5-10 min after application and were maximal after 20-40 min. These data show pronounced suppression of inflammation-induced nociception by dipyrone and they suggest that the spinal cord is a major site of action of this compound.

Analgesics↗