PubMed HealthSearch

Biomedical subjects

B C Shyu

Publications and source records attributed to B C Shyu.

At least 19 recordsLinked to original sources

Neurophysiological, pharmacological and behavioral evidence for medial thalamic mediation of cocaine-induced dopaminergic analgesia.

These studies examined the effects of cocaine on thalamic neurons that respond maximally either to noxious or to innocuous somatic stimulation. Cocaine attenuated high intensity electrically-evoked nociceptive responses of all 25 units studied in the parafascicular and central lateral nuclei of the medial thalamus. A dose of 1 mg/kg intravenously (i.v.) suppressed medial thalamic unit discharge evoked by both noxious somatic stimulation (49.4 +/- 8.7% of control response) and spinal cord stimulation (76.2 +/- 6.6% of control response). The effect of cocaine on unit responses to noxious somatic stimulation was dose-related in the range of 0.3-3.5 mg/kg i.v. and was attenuated by eticlopride, a D-2 selective dopamine receptor antagonist. Morphine also suppressed noxious somatic evoked responses of medial thalamic units in a dose-dependent manner. Units in the lateral (ventrobasal) thalamus (n = 4) that responded only to innocuous stimuli were not affected by cocaine at doses up to 3.5 mg/kg i.v. Ibotenic acid lesions in the parafascicular nucleus of the medial thalamus attenuated the analgesic effect of cocaine in the formalin test. These results suggest that both cocaine and the parafascicular nucleus interact with dopaminergic mechanisms that attenuate nociceptive spinal projections to the medial thalamus.

Analgesics

Thalamic nociceptive mechanisms in cats, influenced by central conditioning stimuli.

Field potentials and single cell activity evoked by tooth pulp (TP) stimulation were studied in the ventrobasal (VB) complex of the cat. The experiments were performed using a conditioning-test paradigm. Evoked cell activity or field potentials following TP stimulation was used as a test. Conditioning stimulus was given to different regions of the thalamic central lateral nucleus (CL). Conditioning electrical stimulation in medial (ML 2.8-3.6 mm) parts of CL induced a depression of the TP evoked response in 10 cells. Stimulation sites in lateral CL (ML 3.6-4.2 mm) induced facilitation in eight cells and decreased activity in seven cells. Tooth pulp evoked field potentials in thalamus were facilitated by a preceding stimulation in lateral CL. Cells in the lateral parts of CL are suggested to induce an increased activity in cells in the VB complex which mediate nociceptive information. This effect is suggested to be mediated via a CL induced disinhibition at a reticular thalamic (RE) or at a VB complex level. The medial parts of CL seem to give a traditional feedback inhibition on VB cells. Such an effect is also suggested to be mediated via the RE complex. The importance of these findings are discussed with relation to changes in the thalamus that may occur following long lasting nociceptive stimulation.

Animals

Properties of single neurons in the cat midsuprasylvian gyrus.

Responses of cells in the midsuprasylvian gyrus (MSSG) of cats were investigated following electrical stimulation of the central lateral nucleus (CL) of the thalamus and tooth pulp, low-threshold cutaneous or visual afferents. Electrical stimulation in CL induced excitation in many cells located in cortical areas 5 and 7. Cells in these areas also received input from somato-sensory and visual afferents. Cells in MSSG showed a wide convergence from tooth pulp, low-threshold cutaneous afferents and from the CL. The majority of wide convergent cells in area 5 were found in layers IV and V, while cells excited by CL and tooth pulp were found in layers II and III. Similarities were found between CL and tooth pulp evoked responses with regard to the excitation-inhibition pattern. The excitation evoked from CL and tooth pulp was less often followed by a hyperpolarizing potential compared to that seen after low-threshold lip, paw and visual afferent stimulation. Stimulation sites in the lateral parts of CL-evoked responses with the shortest latencies in area 5. In this part of the cortex, short latency synaptic potentials were found in cells in superficial layers. In the same area, synaptic potentials of short latency were also evoked by electrical stimulation of tooth pulp, lip and paw. Light-flash stimulation evoked responses with the shortest latencies in area 7. The results of this study demonstrate that putative nociceptive information reaches the parietal association cortex and that part of this input may be relayed via CL. We suggest that the excitatory influences of nociceptive and CL stimulation is related to behavioral arousal and attention mechanisms.

Afferent Pathways

Effects of sympathetic stimulation on C-fibre response after peripheral nerve compression: an experimental study in the rabbit common peroneal nerve.

Non-myelinated C-fibre responses during sympathetic trunk stimulation were studied in rabbit common peroneal nerve 2 weeks after the nerve had been subjected to compression at 400 mmHg for 30 min. Our previous studies have demonstrated that during sympathetic trunk stimulation the compound action potential of uninjured somatic C-fibres is characterized by a reduced amplitude and an increased latency. In the present study, nerve compression changed the C-fibre response to sympathetic stimulation. Three out of eight nerves reacted to nerve compression by increased C-fibre compound action potential amplitude in response to sympathetic stimulation. In three other rabbits with compressed nerves the C-fibre action potential amplitude was unchanged, and in the remaining two rabbits the action potential amplitude was decreased during sympathetic stimulation. The action potential latency increased in all tested compressed C-fibres. The phenomenon of increased C-fibre amplitude during sympathetic activation has not been observed in uninjured nerves. As in uninjured nerves, noradrenaline infusion produced an increased C-fibre action potential amplitude and latency in six animals. Sympathetic stimulation did not affect the A-fibre response. These results indicate that sympathetic activity influences the conduction properties in C-fibres of somatic origin and that the response can be changed after a nerve injury. The findings may be of importance for the understanding of pain aggravation in different types of nerve injuries during increased sympathetic activity.

Action Potentials

Projection from the thalamic intralaminar nuclei on the isocortex of the rat: a surface potential study.

Cortical surface potentials evoked from thalamic intralaminar nuclei have been studied in rats anaesthetized with chloralose. Stimulation with low current intensity in central lateral nucleus (CL), evoked potentials in large areas of the rat isocortex. In the posterior parietal cortex responses with a short latency negativity were evoked which followed high frequency repetitive stimulation. Its latency and ability to follow high frequency stimulation indicated a monosynaptic connection from CL to this part of the cortex. The short latency potential was followed by a second negativity with longer latency and varying amplitude. This second negativity did not follow repetitive stimulation exceeding 10 Hz, and was also reduced by supplementary doses of anaesthetics, indicating a polysynaptic origin. Stimulation at different CL sites elicited cortical potentials with short latency in a topographical pattern. Laminar analysis in the parietal and motor cortex suggested both a superficial and a deep layer termination of afferents from CL. Similar topografical relations and afferent layer distributions have previously been found in cats. The role of the thalamocortical projection from CL to parietal cortex in arousal, attention and pain mechanisms is discussed.

Action Potentials

Effects of nerve compression or ischaemia on conduction properties of myelinated and non-myelinated nerve fibres. An experimental study in the rabbit common peroneal nerve.

Compound action potentials of both myelinated (A) and non-myelinated (C) fibres in the common peroneal nerve of rabbits were studied during and after acute, graded compression of the nerve at 200 or 400 mmHg applied for 2 h or during ischaemia created by nitrogen inhalation or aortic occlusion. Compression of the nerve at 200 mmHg blocked the AI component (large myelinated fibres) after about 23 min, while compression at 400 mmHg shortened this time to 11 min. The A2 component (thinner myelinated fibres) had a lower conduction velocity and a higher resistance to compression. There was just a slight decrease in conduction velocity of the non-myelinated fibres when the nerves were compressed at 200 mmHg for 2 h. However, compression at 400 mmHg for 2 h induced a marked deterioration of amplitude and conduction velocity of the C-fibres. There was an incomplete restitution of function of A- and C-fibres during 2 h of recovery. The thinner myelinated fibres were more susceptible to deprivation of oxygen than the thicker ones, while non-myelinated fibres differed in response according to method of ischaemia induction. It is concluded that non-myelinated fibres are very resistant to compression and a very high pressure (greater than 400 mmHg) is needed to affect these fibres.

Animals

Effects of sympathetic stimulation on C-fibre responses in rabbit.

Unmyelinated C-fibre responses to electrical stimulation were recorded in common peroneal, sural and tibial nerves of rabbits. Three distinct C elevations, here called C1, C2 and C3, were recorded. C2 is probably of somatic origin because it was depressed due to collision by peripheral stimulation of cutaneous receptors. The conduction velocity of C3 corresponded to that of sympathetic post-ganglionic fibres. During sympathetic trunk stimulation the A-fibre responses were not significantly changed while C responses, especially C2, were reduced in amplitude and slightly delayed. The C-fibre responses were also influenced by intra-arterial infusion of noradrenaline. In most cases, the latency of the response was increased. The effect of sympathetic stimulation was completely blocked by hexamethonium, and partly blocked by phentolamine, an adrenergic alpha-receptor blocking agent which also blocked the effect of noradrenaline. The findings suggest that there are adrenergic receptors distributed along unmyelinated somatic afferent fibres. Sympathetic activity may release noradrenaline in the peripheral nerve, resulting in changed conductive properties in unmyelinated fibres transmitting sensory information.

Adrenergic alpha-Antagonists

Sympathetic and noradrenaline effects on C-fibre transmission: single-unit analysis.

Single afferent unmyelinated fibres were dissected from the otherwise intact sural nerve in anesthetized rabbits. The sympathetic trunk could be stimulated via electrodes implanted through the abdomen. The response in single C fibres was elicited by electrical stimulation in the cutaneous innervation area of the fibre. Sympathetic stimulation (8 Hz, 1 ms pulses, 5 mA for 60 s) increased the latency in all tested C fibres (2.0% +/- 0.8%, mean +/- SD, n = 17). In 48% of the units the amplitude of the action potential decreased (26.4% +/- 12.3%) during sympathetic stimulation. Infusion of noradrenaline (5 micrograms min-1) increased (7.7% +/- 4.1%) the latency in all units and increased (36.9% +/- 29.8%) the amplitude of 25% of the units. The effects of sympathetic stimulation and noradrenaline infusion were blocked by pre-treatment with phentolamine (3 mg kg-1 i.v.). The results suggest that catecholamines change the membrane properties of unmyelinated fibres.

Action Potentials

Field potential analysis of the cortical projection of the central lateral nucleus in the cat.

A previous field potential study has indicated a monosynaptic projection of fibres from the central lateral nucleus (CL) to the mid-suprasylvian gyrus (MSSG). The present study, which is based on an analysis of current source density (CSD), aims to investigate further the sites of major localized synaptic activities in different layers of the MSSG after electrical stimulation in the CL. An initial positive surface potential was evoked in the MSSG with a latency of 3-5 ms and followed by a large negative potential with a peak latency of 8-15 ms. The initial positivity was only found in the rostral part of the MSSG, which corresponds to area 5. The positivity reversed in deeper layers. The CSD analysis showed a sink at a depth from 650 to 1050 microns. A corresponding source was found more superficially at 400-600 microns. This indicates that CL fibres have an excitatory synaptic termination on the soma or proximal dendrites of neurons in layers III and IV. The surface negative potential reversed at the border between layers II and III, suggesting a superficial CL projection. The CSD analysis of potentials in superficial layers showed a sink appearing between the pial surface and a depth of 350 microns, and a source lying in layers below. This indicates a depolarization of apical dendrites of cells in layers II and III. The superficial sink appeared in a large part of the MSSG. Application of a solution of 0.5% gamma-aminobutyric acid (GABA) on the surface of the cortex blocked the superficial sink and source and revealed a prominent sink current in layers III and IV in agreement with a deep termination of CL fibres. Application of a solution of 25 mM DL-2-amino-5-phosphono-valeric acid (APV) abolished CL-evoked cortical responses indicating that N-methyl-D-aspartate (NMDA) receptors are involved in the cortical activation. The CSD analysis confirms that CL has a wide superficial projection to the MSSG. It also confirms a deeper monosynaptic projection from CL to area 5.

Animals

Isometric muscle tension generated by masseter stimulation after prolonged alteration of the consistency of the diet fed to growing rats.

The forces developed by the masseter muscle and the diet-related changes were studied in situ. The active tetanic tension was measured indirectly by recording the forces applied to the mandible in four different predetermined interincisal distances. The highest tension developed in all the experimental groups was with an interincisal distance of 11 mm. The tetanic tension was significantly lower in rats fed a soft diet than in those fed a normal diet. This difference might be due to the smaller muscle fibres in rats with decreased functional demand. The changes in the masticatory muscles may influence the tension applied to the facial skeleton and cause the alteration in the craniofacial growth previously found in rats fed a soft diet.

Animals

Differential stress effects on responses to noxious stimuli as measured by tail-flick latency and squeak threshold in rats.

In the present study tail-flick latency (TFL) and squeak threshold (ST) were investigated in different environmental conditions in normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The TFL did not vary significantly during the testing period (120 min). The ST increased gradually and significantly with time when measured in rats restrained in the TFL test tube. Freely moving rats transferred to the TFL test tube showed a marked decrease of the ST. During the stay in the TFL test tube, the ST value increased gradually. Also after transfer from the test tube to the home cage the threshold increased to the same level as freely moving rats. There were no significant differences in these effects between WKY and SHR. Naloxone (1 mg kg-1 i.v.) decreased the ST in both freely moving and restrained animals of either strain. Intravenous injection of morphine (mg kg-1) gave a pronounced threshold increase of ST in both groups. It is suggested that animals restrained in the TFL test tube become hyperalgesic. The adaptation to stress is reflected in the ST but not in the TFL. Squeak threshold appears to be influenced by a tonically active endorphin system.

Animals

Course and mode of action of descending system conveying nucleus raphe magnus induced inhibition of flexion reflex in rats.

In lightly anaesthetized rats, the latencies and magnitudes of heat-evoked withdrawal reflexes from the hindlimb were measured electromyographically. Low-intensity (20-50 microA) stimulation of the nucleus raphe magnus (NRM) resulted in an inhibition of the flexion reflex (commonly referred to as analgesia) as evidenced by increased latency and decreased amplitude. The effect lasted for several minutes after the stimulation was terminated. Following lesions of the dorsolateral funiculus (DLF) at the neural thoracic levels 7-8, baseline latencies were reduced and the effect of the NRM stimulation was abolished. Lesions of the DLF at lumbar level 1 resulted in unaltered baseline latencies with persistence of the inhibitory effect of NRM stimulation. The results of the present experiment show that pathways exerting a tonic inhibition of the withdrawal reflex, and mediating the effect of electrical stimulation from the NRM, descend in the DLF at the thoracic level of the spinal cord. At the lumbar level, there is a shift away from the DLF. The antinociceptive effect of 20 microA NRM stimulation was partly reduced by pretreatment with the serotonin synthesis inhibitor para-chlorophenylalanine (PCPA) or the opiate naloxone (1 mg kg-1 i.v.). In animals pretreated with PCPA, naloxone (1 mg kg-1 i.v.) completely abolished the analgesic effect of the stimulation. Thus, both serotonergic and opioid systems may be implicated in mediating the analgesia. With 50 microA stimulation the same treatment only partly attenuated the NRM-induced analgesia, indicating an additional non-serotonergic and non-opioid mechanism which requires a higher current intensity for its activation.

Animals

Influence of changes of tooth temperature on reflex and central activity evoked by stimulation of tooth pulp afferents.

The importance of the temperature of the dentine was studied in teeth prepared for electrical stimulation. During experiments with the mouth open, the temperature of teeth covered by cement was normal. The digastric EMG and the brainstem--evoked response following electrical stimulation of the tooth pulp as well as the threshold for eliciting a jaw-opening response remained constant throughout prolonged experiments. However, heat produced by the cement used to fixate the tooth electrodes could have damaged the tooth if the dentine temperature had exceeded 45 degrees C. A careful preparation of the tooth pulp by repeated application of thin layers of cement allowed an adequate preparation without damage to tooth pulp afferents.

Animals

Localized responses in the midsuprasylvian gyrus of the cat following stimulation of the central lateral nucleus in thalamus.

Evoked responses were mapped in the cerebral cortex following low intensity electrical stimulation in serial penetrations of the medial and intralaminar nuclei of the thalamus of the cat. A projection was found from one of the intralaminar nuclei, the central lateral nucleus (CL) to the midsuprasylvian gyrus, mainly areas 5 and 7. The projection is suggested to be direct, since the evoked responses had a short latency initial positivity. The most characteristic type of response consisted of this early positivity followed by two successive negativities. The earlier, so called first negativity followed high frequency stimulation and was recorded in a smaller area of the cortex than the later, so called second negativity. The first negativity is suggested to depend on monosynaptic depolarization and activation of cortical cells. The second negativity failed at frequencies higher than 10 Hz and was strongly depressed by the administration of barbiturates; it is suggested to depend on polysynaptic depolarization and cellular activity. In electrode penetrations of the cortex both negativities reversed at the border between cortical layers II and III, indicating a superficial termination of thalamic afferents in the cortex. The cortical evoked response to CL stimulation was facilitated by light mechanical and low intensity electrical stimulation of the periphery, as well as by electrical stimulation of the tooth pulp. The possible significance and function of this projection is discussed in relation to arousal, attention and pain.

Animals

Effects of naloxone on dental pain threshold following muscle exercise and low frequency transcutaneous nerve stimulation: a comparative study in man.

Previous studies have shown that muscle exercise and low frequency transcutaneous nerve stimulation (TNS) give rise to an analgesic effect in humans and animals. Endorphin has been proposed to mediate this analgesia. In this investigation, the effect of muscle exercise and low frequency TNS, on dental pain thresholds was studied and the possible involvement of endorphinergic mechanisms was investigated using naloxone as an antagonist. Dental pain thresholds were measured in 11 volunteers following leg or arm exercise and after low frequency TNS of the hands or face. After exercise (20 min) or stimulation (30 min) either 0.8 mg naloxone (2 ml) or saline (2 ml) was injected i.v. in a double-blind fashion. Pain thresholds were measured repetitively before and after exercise or stimulation. Both leg and arm exercise increased pain threshold. Stimulation of the hands also increased pain threshold, but less than arm exercise. A marked increase in pain threshold was seen after face stimulation. These changes in pain threshold were unaffected following injections of either naloxone or saline, except for an early and short-lasting reduction when naloxone was injected following arm exercise. The increases in pain threshold following muscle exercise and after low frequency TNS, showed similarities suggesting that a common mechanism might be involved. The pain threshold increase after arm exercise could only be partially mediated by endorphinergic mechanisms.

Adult

Circulatory events following spontaneous muscle exercise in normotensive and hypertensive rats.

In previous studies we have shown that spontaneously hypertensive rats (SHR) develop a running behaviour and, secondary to the running behaviour, develop an endorphin-mediated analgesic effect. In the present study the role of the central endorphin system in the cardiovascular responses to spontaneous exercise in normotensive Wistar Kyoto rats (WKY) and SHR was investigated. The experimental design allowed us to record mean arterial pressure (MAP) and heart rate (HR) continuously for more than 1 week without interfering with the daily activities of the animals. They were active in running wheels during the dark period (19.00-07.00 h) and the activity was accompanied by a marked rise in HR. In SHR, a clear depression of blood pressure lasting for about for about 50 min was noted following each running period. The MAP during the post-running depression was 131.4 +/- 1.6 mmHg which was significantly lower than the pre-running control value (145.2 +/- 2.3 mmHg, P less than 0.01). In contrast, MAP in the post-running period in WKY was not significantly different from the pre-running values. In addition, the depression period of SHR had a mean post-running length of 49.7 +/- 3.4 min, which is significantly longer than in the WKYs (37.8 +/- 3.5 min, P less than 0.05). In control rats, naloxone infusion had no effect on blood pressure but a marked bradycardia was observed. In nine running SHR receiving a naloxone infusion, their MAP during the depression period was not different from the control pressure. Our study indicates that endorphin systems are involved in the regulating of blood pressure and HR during muscle exercise in SHR. These systems trigger the transient depression of blood pressure observed immediately after a running period in the SHR.

Animals

Circulatory depression following low frequency stimulation of the sciatic nerve in anesthetized rats.

Earlier experiments have shown that afferent electrical stimulation of the sciatic nerve for 30 min induces a long-lasting post-stimulatory endorphin-dependent decrease in blood pressure in awake spontaneously hypertensive rats (SHR). In the present study we have examined whether this depressor response can be observed also in anesthetized SHR. The sciatic nerve was stimulated for 30 min with low-frequent (3 Hz) trains of impulses and the changes in blood pressure, heart rate and renal nerve activity were observed during the stimulation and in the post-stimulatory period. Animals anesthetized with Nembutal, Althesin and N2O did not show any post-stimulatory depression. In contrast, during chloralose anesthesia combined with muscle paralysis with Flaxedil, sciatic nerve stimulation induced a long-lasting post-stimulatory decrease in blood pressure due to central inhibition of sympathetic activity. The decrease in blood pressure could be prevented by naloxone and was therefore likely to be mediated via activation of central endorphin systems.

Alfaxalone Alfadolone Mixture