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PubMed2004

Effects of propofol and sevoflurane on the excitability of rat spinal motoneurones and nociceptive reflexes in vitro.

BACKGROUND: Spinal actions of halogenated ethers are widely recognized, whereas spinal actions of intravenous anaesthetics like propofol are less clear. The aim of this study was to compare the spinal effects of propofol and sevoflurane. METHODS: We used an isolated spinal cord in vitro preparation from rat pups and superfused the anaesthetics at known concentrations. Responses of motoneurones to single and repetitive C-fibre intensity stimulation (trains of 20 stimuli at 1 Hz) of a lumbar dorsal root were recorded from the corresponding ventral root via a suction electrode. RESULTS: Stimulation trains produced a wind-up of action potentials in motoneurones. Both propofol and sevoflurane produced a significant concentration-dependent depression of the evoked wind-up, although at clinically relevant concentrations sevoflurane exhibited a larger intrinsic efficacy. Applied at anaesthetic concentrations, sevoflurane 250 micro M abolished action potentials whereas propofol 1 micro M only produced a reduction close to 50%. At these concentrations, sevoflurane produced a large depressant effect on the monosynaptic reflex whereas propofol was ineffective. CONCLUSIONS: Sevoflurane produces large inhibitory effects on nociceptive and non-nociceptive reflexes which are likely to contribute to immobility during surgery. Compared with sevoflurane, propofol appears to have much weaker effects on spinal reflexes such as those recorded in an isolated preparation.

Anesthetics, Inhalation↗
PubMedDate not supplied

Temporal specificity of long-term depression in parallel fiber--Purkinje synapses in rat cerebellar slice.

The phenomenon of cerebellar long-term depression (LTD), a decrease of synaptic strength between the parallel fibers (PFs) and Purkinje cells after conjunctive activation of PFs and the climbing fibers (CFs), is implicated as a cellular mechanism for motor learning. We have characterized a field-potential recording technique in cerebellar slice and have used the technique to examine the temporal conditions for cerebellar LTD induction in an attempt to examine the relevance of LTD to associative conditioning. Interstimulus intervals (ISIs) between onsets of PF and CF activation and the number of paired stimuli (pairings) were examined. LTD has distinct temporal specificity that seems to be constrained by inhibitory interneurons and can be masked by excessive stimulation. When 100 paired stimuli were given to PFs and CFs, LTD was induced with an ISI of 250 msec (PF activation preceding CF activation). In contrast, a smaller forward (125 msec), simultaneous (0 msec), or backward (-250 msec) ISIs were not effective for inducing LTD. However, the blockade of GABAA receptor-mediated inhibition made it possible to induce LTD with 100 pairs of simultaneous stimulations. Furthermore, by increasing the number of pairings to 600, significant LTD was observed with all four interstimulus intervals. These results suggest that temporal conditions for LTD induction share some similarity to associative learning of discrete motor responses.

Animals↗
PubMed2001

Aceclofenac increases the synthesis of interleukin 1 receptor antagonist and decreases the production of nitric oxide in human articular chondrocytes.

OBJECTIVE: Interleukin 1 receptor antagonist (IL-1Ra) may play an important role in cartilage degradation by inhibiting IL-1 activity and therefore blocking IL-1 stimulation of prostaglandin E2 (PGE2) synthesis. Nitric oxide (NO) formation is increased during inflammation. High concentrations of NO exert negative effects on chondrocyte functions. We investigated the possible effects of 3 different nonsteroidal antiinflammatory drugs (NSAID; aceclofenac, piroxicam, aspirin) on IL-1Ra and NO production in human articular chondrocytes. METHODS: Normal and osteoarthritic (OA) cartilage samples were obtained from autopsy and prosthetic joint surgery, respectively. Chondrocytes were isolated and stimulated with 4 different stimuli: IL-1, tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), and insulin-like growth factor (IGF). The 3 NSAID were added simultaneously to each different concentration of stimulus. IL-1Ra was measured in supernatant by ELISA; nitrites were quantified by the Griess reaction; PGE2 level was measured by enzyme immunoassay. RESULTS: OA samples spontaneously produced higher levels of IL-1Ra than normal samples (130+/-2.3 vs 30+/-3.1 pg/mI). IL-1, TNF-alpha, and LPS produced dose dependent increases in synthesis of IL-1Ra. In their presence, IL-1Ra was detected in supernatant at 48 h, but its highest level was measured at 144 h. The most potent stimulus was IL-1, followed by TNF-alpha. Fetal bovine serum and IGF in turn did not modify the basal levels of IL-1Ra. In contrast to piroxicam and aspirin, aceclofenac 10 microg/ml and TNF-alpha 10 ng/ml increased almost 46 times the basal amount of IL-1Ra produced by OA chondrocytes. Additionally, aceclofenac and aspirin inhibited NO synthesis. Finally, the 3 NSAID reduced the levels of PGE2 detected after stimulation with IL-1. CONCLUSION: Proinflammatory stimuli induce IL-IRa synthesis in human articular chondrocytes. Aceclofenac may modulate PGE2 production by increasing IL-IRa production and decreasing NO synthesis. Some NSAID exert diverse prostaglandin independent effects.

Aged↗
PubMed1992

[Neocortex neuronal reactions induced by substantia innominata stimulation in cats].

Neuronal impulse activity in the sensorimotor cortex after Substantia Innominata (SI) stimulation has been studied in cats during conditioned placing with food reinforcement. SI stimulation was delivered 1 or 3 seconds before the conditioned sound stimuli. The results of the investigation show that SI stimulation does not change sensorimotor cortex impulse activity but at the same time it inhibits the background activity. Reactions of 32% (after 1 s) and 33% (after 3 s) of the somatosensory cortex neurones were increased to conditioned stimuli and conditioned movement after preliminary SI stimulation. The appearance of impulse responses in some neurones which showed no initial reactions to conditioned stimuli was caused by SI stimulation. Preliminary SI stimulation may cause not only excitatory but also inhibitory effect on somatosensory cortical neurones. In case of 1 s interval between SI stimulation and conditioned stimuli presentation there were only 6% of cells with such inhibition, but in case of 3 s interval there were 33% of such reactions. SI stimulation shortened the latencies of the conditioned movement 2-3 times. Modulatory influence of acetylcholine from SI neurones to neocortical activity is discussed.

Animals↗
PubMedDate not supplied

[Neuronal activity in self-stimulation zones of the hypothalamus in motivational and emotional states induced by electrical and natural stimuli].

Study of neuronal activity in hypothalamus areas of self-stimulation in rats showed two types of neurones. Some of them had an increased frequency at food and water deprivation and they had maximum activation at current stimulation, eliciting motivational behaviour. Others had maximum activation at current level, eliciting self-stimulation effects, some of these neurones had positive activating relation to satisfaction of food requirements. The obtained data are considered as morphofunctional substrate of motivational and emotional states.

Animals↗
PubMed1998

Differential regulation of FAK+ and PYK2/Cakbeta, two related tyrosine kinases, in rat hippocampal slices: effects of LPA, carbachol, depolarization and hyperosmolarity.

FAK+, an isoform of focal adhesion kinase preferentially expressed in brain and PYK2/Cakbeta (proline-rich tyrosine kinase 2/cell adhesion kinasebeta) are two related cytoplasmic tyrosine kinases. They are candidates for coupling electrical activity and stimulation of neurotransmitter receptors to short and long-term changes in synaptic properties, cytoskeletal organization and gene expression in neurons. As the same set of stimuli appear capable of stimulating FAK and/or PYK2 in non-neuronal cells and in cell lines with neuronal characteristics, we investigated the selectivity of regulation of these two kinases in mature nervous tissue. Using rat hippocampal slices, we compared the regulation of FAK+ and PYK2 by stimuli known to be active on one or the other of these two kinases in other cell types: lysophosphatidic acid (LPA), carbachol, depolarization, and hyperosmolarity. Phosphorylation of FAK+ was markedly increased by carbachol and LPA. Carbachol effects occurred via activation of M1 muscarinic receptors and nicotinic receptors. The effects of carbachol and LPA were prevented by protein kinase C inhibitors, whereas 8-Br-cAMP attenuated the effects of carbachol but not of LPA. Tyrosine phosphorylation of PYK2 but not of FAK+ was very strongly enhanced by depolarization and hyperosmolarity. This study and our previous results show that FAK+ and PYK2 are regulated differentially in hippocampal slices: FAK+ is phosphorylated on tyrosine in response to stimulation of G protein-coupled receptors, whereas PYK2 is mainly sensitive to depolarization and hyperosmolarity. Thus, FAK+ and PYK2 may provide specific and separate links between activation of neurotransmitters receptors, depolarization and tyrosine phosphorylation in mature hippocampus.

Animals↗
PubMed1991

Empirical evidence against the 'cycle time dependency' assumption.

The interpretation of the 'cardiac cycle time effect', also named 'time-dependent primary bradycardia' by the Laceys, who first observed it, has been controversial in psychophysiology. Unconfounded evidence for the dependence of a vagal effect of psychological stimuli on time of stimulation within the cardiac cycle has been missing to date. An experiment in which the subjects could not anticipate the occurrence of the stimuli (short tones of a specific frequency that had to be counted) was performed. The data reduction procedure secured unambiguous interpretation of the data with respect to time-dependency or no time-dependency. No indication of any kind of cycle time dependency of the vagal effect was found.

Acoustic Stimulation↗
PubMed1999

Confocal imaging of the subcellular distribution of phosphatidylinositol 3,4,5-trisphosphate in insulin- and PDGF-stimulated 3T3-L1 adipocytes.

The activation of phosphatidylinositol 3-kinase (PI 3-kinase) and production of PtdIns(3,4,5)P(3) is crucial in the actions of numerous extracellular stimuli, including insulin-stimulated glucose uptake. Platelet-derived growth factor (PDGF) also stimulates PI 3-kinase, but only weakly promotes glucose uptake when compared with insulin. Insulin and PDGF have thus been proposed to have differential effects on the subcellular targeting of PI 3-kinase. However, owing to a lack of suitable methodologies, the subcellular localization of the PtdIns(3,4,5)P(3) generated has not been examined. The pleckstrin-homology (PH) domains of the nucleotide exchange factors, ADP-ribosylation factor nucleotide-binding-site opener (ARNO) and general receptor for 3-phosphoinositides (GRP1), which have a high affinity and specificity for PtdIns(3,4,5)P(3), were fused to green fluorescent protein and used to examine the subcellular localization of PtdIns(3,4,5)P(3) generation in living 3T3-L1 adipocytes. PtdIns(3,4,5)P(3) was produced almost exclusively in the plasma membrane in response to both agonists, although the response to insulin was greater in magnitude and occurred in considerably more cells. The results suggest that the greater ability of insulin to stimulate glucose uptake may be the result of its ability to generate significantly more plasma-membrane PtdIns(3, 4,5)P(3) than PDGF. ARNO and GRP1 are nucleotide exchange factors for the small GTP-binding protein ADP-ribosylation factor 6 (ARF6). The inability of a constitutively active GTPase-deficient mutant of ARF6 (ARF6-Q67L; Gln(67)-->Leu) to cause glucose transporter GLUT4 translocation suggests that activation of this pathway is not sufficient to cause GLUT4 translocation.

3T3 Cells↗
PubMed1995

Physiological characterization of pretectal neurons projecting to the lateral posterior-pulvinar complex in the cat.

Pretectal neurons projecting to the lateral posterior-pulvinar complex (LP-P) in cats were electrophysiologically identified by their antidromic activation from the LP-P. Their responses to various visual stimuli and to electrical stimulation of the optic chiasm and the lateral geniculate nucleus (LGN) were characterized. In retrograde double-labelling experiments, the pretectal projections to the LP-P and to the LGN were tested for possible overlap. Forty-five neurons were antidromically activated from the LP-P; 55% of them could also be activated orthodromically from the optic chiasm. Most antidromically activated neurons responded to rapid movements of large textured visual stimuli as well as to 'on' or 'off' visual stimulation with short bursts. When stimulated with a slowly moving, large, structured visual stimulus, most cells showed a slight but significant activity increase. None of the neurons projecting to the LP-P was also activated antidromically from the LGN. Thus, the two populations are separate. This is supported by the results from the retrograde double-labelling experiments. None of the LP-P projecting neurons showed any directional selectivity to slow movements of large visual stimuli, a property by which pretectal neurons projecting to the inferior olive are characterized. Thus, neurons projecting to the LP-P do not bifurcate to the inferior olive. Response properties of neurons projecting to the LP-P were very similar to those of the 'jerk' neurons described by Schweigart and Hoffmann (Exp. Brain Res., 91, 273-283, 1992); therefore we believe them to be identical.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Paired-pulse magnetic stimulation of the human motor cortex: differences among I waves.

1. In paired-pulse cortical stimulation experiments, conditioning subthreshold stimuli suppress the electromyographic (EMG) responses of relaxed muscles to suprathreshold magnetic test stimuli at short interstimulus intervals (ISIs) (1-5 ms) and facilitate them at long ISIs (8-15 ms). 2. We made paired-pulse magnetic stimulation studies on the response of the first dorsal interosseous muscle (FDI) produced by I1 or I3 waves using our previously reported method which preferentially elicits one group of I waves when subjects make a slight voluntary contraction. In some experiments the conditioning and test stimuli were oppositely directed, in the others they were oriented in the same direction. Single motor unit responses were recorded with a concentric needle electrode, and surface EMG responses with cup electrodes. 3. In post-stimulus time histograms (PSTHs) of the firing probability of motor units, the peaks produced by I3 waves were decreased by a subthreshold conditioning stimulus that preferentially elicited I1 or I3 waves at an ISI of 4 ms. The amount of decrement depended on the intensity of the conditioning stimulus. The stronger the conditioning stimulus, the greater the suppression. In contrast, the peaks produced by I1 waves were little affected by any type of subthreshold conditioning stimulus, given 4 ms prior to the test stimulus. At an ISI of 10 ms, a subthreshold conditioning stimulus slightly decreased the size of the peak produced by the I3 waves, but did not affect the peaks evoked by I1 waves. 4. Surface EMGs showed that a subthreshold conditioning stimulus suppressed the responses produced by I3 waves irrespective of its current direction (anterior or posterior). Both the amount and duration of suppression depended on the intensity of the conditioning stimulus, but not on its current direction. Both parameters increased when the intensity increased. At a high intensity conditioning stimulus, suppression was evoked at ISIs of 1-20 ms, compatible with the duration of GABA-mediated inhibition found in animal experiments. Responses produced by I1 waves were little affected by any type of subthreshold conditioning stimulus. 5. We conclude that a subthreshold conditioning stimulus given over the motor cortex moderately suppresses I3 waves but does not affect I1 waves. The duration of suppression of the I3 waves supports the idea that this is an effect of GABAergic inhibition within the motor cortex.

Adult↗
PubMed2006

Noxious cold stimulation induces mitogen-activated protein kinase activation in transient receptor potential (TRP) channels TRPA1- and TRPM8-containing small sensory neurons.

Two cold-sensitive transient receptor potential (TRP) channels, TRPA1 and TRPM8, have been identified and considered interesting because of their possible roles in thermosensation, nociception and other functions. Recently, we have reported that the phosphorylation of extracellular signal-regulated protein kinase and p38 mitogen-activated protein kinase occurred in primary afferent neurons in response to noxious heat stimulation of the peripheral tissue, i.e. activity-dependent activation of extracellular signal-regulated protein kinase and p38 in dorsal root ganglion neurons. In the present study, we investigated the phosphorylation of extracellular signal-regulated protein kinase, p38, and c-Jun N-terminal kinase in the rat dorsal root ganglion by cold stimulation using immunohistochemistry. Cold stimuli (28-4 degrees C) were applied by immersion of the hind paw into a water bath (six times of 10 s stimulation and 10 s interval, total 2 min). Noxious cold stimulation induced phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38, but not phosphorylated-c-Jun N-terminal kinase, in small to medium diameter sensory neurons with a peak at 2 min after stimulation. We found that a cold stimulation at 4 degrees C showed a marked increase in the number of activated neurons. Furthermore, double staining for phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38 showed no colocalization in the dorsal root ganglion neurons. We then performed double-labeling experiments for TRPA1 and TRPM8 mRNA and phosphorylation of mitogen-activated protein kinase. The majority of phosphorylated-extracellular signal-regulated protein kinase-positive neurons also expressed TRPM8 mRNA, whereas phosphorylated-p38 heavily colocalized with TRPA1 mRNA after noxious cold stimulation. Our data suggest that the noxious, but not innocuous, cold stimulation in vivo induced differential activation of extracellular signal-regulated protein kinase and p38 pathways in each subpopulation containing TRPA1 or TRPM8 in dorsal root ganglion.

Animals↗
PubMed1993

A possible feline model for human blepharospasm.

'Benign essential blepharospasm' is a human eyelid disorder of unknown aetiology characterized by involuntary, bilateral, and disabling spasmodic contracture of the orbicularis oculi muscle. Treatments are frequently disappointing. Here we report what might be a first step toward developing an animal model for exploring mechanisms of the disorder and potential treatments. We surgically implanted stimulating electrodes into brain areas known to supply input to the lateral division of the facial nerve nucleus to induce blinking by electrical stimulation. Single-pulse stimuli at or near the facial, parabrachial, red, and interstitial nuclei produced consistent stimulus-induced eyelid contractions. Responses were ipsilateral to stimulation, except for the interstitial nucleus where contralateral responses occurred. Little or no other movements of the face, head, or body occurred at eye-blink threshold voltages. When these sites were stimulated with pulse trains, eyelid closures followed stimulus frequency and tended to fuse into constant closure. Thresholds at each stimulus site remained constant during three days of testing. Drug treatments produced no consistent effect on eye-blink threshold from any stimulation site, even when general behaviour was affected. We conclude that these input pathways to the facial nucleus may contribute to blepharospasm and that future neurochemical and electrophysiological study of these pathways may produce a suitable animal model for understanding this disorder.

Animals↗
PubMed1994

Splanchnic and somatic afferent convergence on cervical spinal neurons of the rat.

The rostral cervical spinal cord is increasingly being considered the source of important propriospinal regulation. To better understand the substrate for this function, we investigated the effects of stimulation of the greater splanchnic nerve (GSN) and both thoracic and cervical somatic afferents on the activity of cervical spinal neurons. Extracellular single-neuron recordings were made in the C2-C5 spinal segments of chloralose-anesthetized, paralyzed, and artificially ventilated rats. Neurons were classified according to their responses to GSN stimulation. Neurons were inhibited by this stimulation as frequently as they were excited. We then studied the characteristics of cervical and thoracic convergent somatic input to each class of neurons. Although all cervical neurons that responded to GSN stimulation responded to electrical stimulation of the iliohypogastric nerve (IHN), only the few neurons that exhibited whole body receptive fields (RF) responded to natural thoracic somatic stimuli. Responses to electrical stimulation of the GSN and IHN were similar for most neurons; most exhibited nociceptive cutaneous RFs in cervical dermatomes. These data indicate that input from cervical somatic afferents and from both thoracic visceral and thoracic somatic afferents converge on individual splanchnic-receptive cervical neurons. Although these neurons exhibited the predicted cervical somatic RFs, responses from thoracic levels did not exhibit discrete RFs, requiring instead more synchronous or more spatially convergent input.

Abdomen↗
PubMedDate not supplied

[Monomodal convergence in the visual system of the alert cat].

In chronic experiments on waking cats, the interaction between signals evoked by simultaneous stimulation of the lateral geniculate body (LGB) and pulvinar was mainly of occlusive type which was more pronounced in the visual than in the associative cortical area. Conditioning stimulation of LGB depressed the response to testing stimulation of the pulvinar at delays of 10 ms. Delays of 20-60 ms facilitated the response. At short delays between the stimuli, the conditioning pulvinar stimulation either did not change significantly the response to testing LGB stimulation or facilitated it. At long (80-200 ms) delays the same conditioning stimulation produced a depression of the response to the testing stimulation. The results obtained point to monomodal convergence in the system of the cat visual analyzer and also to a relative autonomy and predominance of the cortical input from LGB and to dependence of pulvinar input functioning on the degree of activation of the geniculo-cortical path.

Animals↗
PubMed1978

Pain perception in man after long term spinal cord stimulation.

Thresholds of non-painful and painful perception for electrical stimuli are not altered significantly during dorsal column stimulation either in the area of induced paresthesia or outside it. After long term stimulation of the dorsal column the thresholds for stimuli are significantly higher within the area of induced paresthesia but not outside it. Median nerve evoked somatosensory cortical potentials are not altered by conditioning or simultaneous DC stimulation. During DCS in three of eight patients only the vibration evoked cortical potentials were attenuated in the early three components of the potential.

Adult↗
PubMed1990

Cardiopulmonary sympathetic afferent excitation of lower thoracic spinoreticular and spinothalamic neurons.

1. Responses of spinoreticular (SRT) and spinothalamic (STT) neurons located in the T7-T9 segments to cardiopulmonary sympathetic afferent (CPS) stimuli were studied in 27 cats that were anesthetized with alpha-chloralose. 2. CPS stimulation excited 32 SRT and 10 STT neurons. Each neuron was also excited by stimulation of the left greater splanchnic nerve (SPL) and had a somatic receptive field that was most commonly located on the upper abdomen and over the lower rib cage. An additional 12 SRT and 3 STT neurons received input from SPL and somatic structures but failed to respond to CPS stimulation. 3. CPS stimulation evoked early responses (23 cells) or both early and late responses (19 cells) that had average latencies of 12.7 +/- 1.8 and 88.2 +/- 13.1 (SE) ms, respectively. Latencies of responses to SPL stimulation were significantly shorter and averaged 8.1 +/- 0.9 and 46.1 +/- 7.1 ms. Magnitudes of early responses to SPL stimulation were significantly greater than responses to CPS stimulation; however, late responses were not different. 4. Responses to CPS stimulation were inhibited by a prior conditioning stimulus applied to SPL. Greatest inhibition occurred at a conditioning-test interval of 40 ms, and inhibition lasted for at least 300 ms. Inhibition of responses to SPL stimulation could be evoked by conditioning stimuli applied to CPS; however, the inhibition was significantly less than that evoked by SPL stimulation on responses to CPS stimulation. 5. Thirty-eight neurons were tested for responses to injection of bradykinin (4 micrograms/kg) into the left atrium. Discharge rate of 17 cells increased from 5 +/- 2 to 12 +/- 4 Hz. Four cells were tachyphylactic to repeated injections. Injections of bradykinin into the thoracic aorta did not significantly alter cell activity. Bilateral cervical vagotomy had no effect on responses to intracardiac bradykinin. 6. The results indicate that lower thoracic SRT and STT neurons are excited by CPS stimuli including noxious stimulation of the heart. However, comparison of these responses with previously reported responses of upper thoracic SRT and STT neurons indicate that there is a decrease in effectiveness of CPS stimuli from upper to lower thoracic segments. Convergence of CPS and abdominal inputs onto lower thoracic pain pathways could explain abdominal pain that is occasionally associated with cardiac disease.

Animals↗
PubMed1999

Effectiveness of sensory stimulation on tactile extinction.

Eleven brain-damaged patients with extinction were asked to report double tactile stimuli before, during, and after optokinetic stimulation and transcutaneous electrical stimulation of the posterior neck region. The goal of the study was to test whether tactile extinction is sensitive to these experimental manipulations in order to better understand the nature of the disorder. Both of these sensory stimulations are known to be effective in modulating only higher-order (cognitive) disorders of spatial coding, such as visual hemineglect, deficit of position sense, hemianesthesia, etc. When applied to the side contralateral to the cerebral lesion, both optokinetic and transcutaneous electrical stimulation significantly affected patients' performances, increasing the amount of detections of contralesional double stimuli. A tendency towards worse performance was observed when sensory stimulation was applied to the ipsilesional side. The reported effectiveness in reducing tactile extinction suggests that the deficit can not be fully ascribed to a peripheral sensory disorder and that it reflects damage to a higher-order cognitive function involved in contralesional space representation or in the deployment of attention to that side of space. The nature of the close relationship between extinction and hemineglect is also discussed from the point of view of extinction as a deficit of space coding.

Aged↗