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Biomedical subjects

M Närhi

Publications and source records attributed to M Närhi.

At least 19 recordsLinked to original sources
PubMed1999

Spreading depression induces expression of calcium-independent protein kinase C subspecies in ischaemia-sensitive cortical layers: regulation by N-methyl-D-aspartate receptors and glucocorticoids.

Spreading depression is a wave of sustained depolarization challenging the energy metabolism of the cells without causing irreversible damage. In the ischaemic brain, sreading depression-like depolarization contributes to the evolution of ischaemia to infarction. The depolarization is propagated by activation of N-methyl-D-aspartate receptors, but changes in signal transduction downstream of the receptors are not known. Because protein phosphorylation is a general mechanism whereby most cellular processes are regulated, and inhibition of N-methyl-D-aspartate receptors or protein kinase C is neuroprotective, the expression of protein kinase C subspecies in spreading depression was examined. Cortical treatment with KCl induced an upregulation of protein kinase Cdelta and zeta messenger RNA at 4 and 8 h, whereas protein kinase Calpha, beta, gamma and epsilon did not show significant changes. The gene induction was the strongest in layers 2 and 3, and was followed by an increased number of protein kinase Cdelta-immunoreactive neurons. Protein kinase Cdelta and zeta inductions were inhibited by pretreatment with an N-methyl-D-aspartate receptor antagonist, dizocilpine maleate, which also blocked spreading depression propagation, and with dexamethasone, which acted without blocking the propagation. Quinacrine, a phospholipase A2 inhibitor, reduced only protein kinase C5 induction. In addition, N(G)(-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, did not influence protein kinase Cdelta or zeta induction, whereas 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate receptor antagonist, and the cyclo-oxygenase inhibitors indomethacin and diclophenac tended to increase gene expression. The data show that cortical spreading depression induces Ca2(+)-independent protein kinase C subspecies delta and zeta, but not Ca(2+)-dependent subspecies, through activation of N-methyl-D-aspartate receptors and phospholipase A2. Even though the signal pathway is similar to the induction described previously in ischaemia for genes implicated in delayed neuronal death, the gene inductions observed here are not necessarily pathogenetic, but may represent a general reaction to metabolic stress.

Animals↗
PubMed1997

Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N-methyl-D-aspartic acid-receptors and phospholipase A2.

Repetitive spreading depression (SD) waves, involving depolarization of neurons and astrocytes and up-regulation of glucose consumption, is thought to lower the threshold of neuronal death during and immediately after ischemia. Using rat models for SD and focal ischemia we investigated the expression of cyclooxygenase-1 (COX-1), the constitutive form, and cyclooxygenase-2 (COX-2), the inducible form of a key enzyme in prostaglandin biosynthesis and the target enzymes for nonsteroidal anti-inflammatory drugs. Whereas COX-1 mRNA levels were undetectable and uninducible, COX-2 mRNA and protein levels were rapidly increased in the cortex, especially in layers 2 and 3 after SD and transient focal ischemia. The cortical induction was reduced by MK-801, an N-methyl-D-aspartic acid-receptor antagonist, and by dexamethasone and quinacrine, phospholipase A2 (PLA2) inhibiting compounds. MK-801 acted by blocking SD whereas treatment with PLA2 inhibitors preserved the wave propagation. NBQX, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate-receptor antagonist, did not affect the SD-induced COX-2 expression, whereas COX-inhibitors indomethacin and diclofenac, as well as a NO synthase-inhibitor, NG-nitro-L-arginine methyl ester, tended to enhance the COX-2 mRNA expression. In addition, ischemia induced COX-2 expression in the hippocampal and perifocal striatal neurons and in endothelial cells. Thus, COX-2 is transiently induced after SD and focal ischemia by activation of N-methyl-D-aspartic acid-receptors and PLA2, most prominently in cortical neurons that are at a high risk to die after focal brain ischemia.

Animals↗
PubMed1995

Associations among different orofacial dysfunctions in 9-11-year-olds.

This study is the second part of a longitudinal investigation on different orofacial dysfunctions in growing individuals. The aim of the present report was to determine, in 219 children with and without articulatory speech disorders, whether certain associations among misarticulations of speech, craniomandibular disorders (CMD), and problems in oral motor skills still were found at the age of 9-11 years, as they had been in these children at the age of 6-8 years. Multiple logistic regression models showed that certain aspects of dental malocclusion such as large overjet, anterior open bite and lateral cross-bite, and certain signs of CMD such as palpatory tenderness of the TMJ, jaw deviation on opening and bruxism were related to misarticulations of speech. Children with sounds produced too far posteriorly seemed to have a smaller maximal opening but larger laterotrusive and protrusive movement capacities of the mandible than children with correct speech articulation. Despite maturation of the oral motor skills with age, among 9-11-year-olds various orofacial dysfunctions still seemed to be associated with each other. This probably indicates fixation of certain speech misarticulations rather than immaturity of the fine motor control.

Articulation Disorders↗
PubMed1994

The neurophysiological basis and the role of inflammatory reactions in dentine hypersensitivity.

Recent studies indicate that intradental A-type nerve fibres are responsible for the sensitivity of dentine and are activated by fluid movements in dentinal tubules (hydrodynamic mechanism). The patency of the tubules affects dentine sensitivity to a great extent. Both A delta- and A beta-type nerve fibres respond to dentinal (hydrodynamic) stimulation in a similar way. Only a few studies have been made on the regional sensitivity of dentine or the receptive areas of intradental nerve fibres. The results indicate that the fibres innervating different parts of coronal dentine are equally sensitive to dentinal stimulation but those in the cervical area may be less responsive. Inflammation in the pulp can considerably alter dentine sensitivity. In dog teeth with chronically exposed dentine, nerve responses to hydrodynamic stimulation were reduced although other functional changes indicated nerve sensitization. This may be due to spontaneously occurring changes in the exposed dentine that block the tubules. In acute experiments on cat and dog teeth with open dentinal tubules, certain inflammatory mediators increase the sensitivity of the responding nerve fibres. It seems that intradental C-fibres do not respond to hydrodynamic stimulation of dentine. They are polymodal and activated when external stimuli reach the pulp proper. They could perhaps mediate the dull pain connected with pulpitis. However, they might also have an important modifying effect on dentine sensitivity because they can release neuropeptides, which function in the inflammatory reactions.

Animals↗
PubMed1992

Relation of dentin sensitivity to histological changes in dog teeth with exposed and stimulated dentin.

The effect of chronic exposure of dentin to the sensitivity of intradental nerves was studied in dogs. The dentin of canine and incisor teeth was exposed one week prior to the experiments in which 34 single fiber units dissected from the inferior alveolar nerve were recorded. In the teeth with acutely bared dentin 36 nerve fibers were tested. SEM of the chronically exposed dentin showed that practically no tubule apertures could be found since the surface was covered with bacteria and oral debris. This coating had to be removed by drilling and acid etching before any responses could be evoked. When compared to the teeth with acutely exposed dentin, the sensitivity of the fibers responding to drilling, probing, osmotic stimulation, and air blasts applied to the dentin was weakened in the chronic cases, in the sense that fewer units of those tested responded. However, cold evoked nerve activity only in some chronically exposed teeth, suggesting sensitization of the nerves. TEM revealed electron-dense substance in the dentinal tubules of the chronic teeth. Some of the material was evidently cellular remnants aspirated from the pulp and some of it, staining more faintly, could be extravasated plasma proteins. In the acute cases the tubules were emptier. Light microscopy showed histological injuries in the pulp-dentin border. It is concluded that the decrease in the responsiveness of the pulp nerve fibers in the chronic cases was due to the changes in the dentin.

Animals↗
PubMed1992

Effect of serotonin (5-HT) and calcitonin gene-related peptide (CGRP) on the function of intradental nerves in the dog.

Several inflammatory mediators including serotonin (5-HT) have been indicated to play a role in the sensitization of intradental nerves. In the present investigation, using the single fibre recording technique, the effect of locally applied 5-HT (1 mg/ml) and calcitonin gene-related peptide (rat CGRP 2 micrograms/microliters) on the function of intradental nerves in the dog was studied. The effect of these substances on the pulpal blood flow was also investigated to check their effective diffusion into the dental pulp. 5-HT induced a low-frequency background firing in 11 out of 30 nerve fibres. The number of fibres responding to probing, air blast and osmotic stimulation was increased significantly after 5-HT application. Three fibres responded to cold stimulation after 5-HT application; no responses were induced before. After CGRP application, a continuous low-frequency firing was induced only in 1 fibre out of 11 and 1 fibre which before did not respond to osmotic stimulation gave responses to saturated glucose. The responses to probing and air blasts were qualitatively unchanged. Local application of either of the substances induced a change in pulpal blood flow. It is suggested that while 5-HT is able to sensitize intradental nerves to various hydrodynamic stimuli, CGRP seems to be less effective. Pulpal inflammation with the release of inflammatory mediators may significantly affect the degree of dentine sensitivity.

Animals↗
PubMed1992

Neurophysiological mechanisms of dentin hypersensitivity.

In hypersensitive teeth pain is typically induced by cold and hot fluids or foods brought to contact with the sensitive dentin or by osmotic and mechanical stimuli. The results of animal experiments indicate that intradental A-type nerve fibres are responsible for the sensitivity of dentin. They are most probably activated by the hydrodynamic mechanism. Thus, their activation is to a great extent dependent on the condition of dentin with either open or blocked dentinal tubules. Blocking of the tubules effectively prevents the nerve activation. Correspondingly, in human experiments, the condition of the dentinal tubules greatly affects dentin sensitivity. In clinical studies significantly more open tubules are found in sensitive compared to non-sensitive areas. However, hypersensitivity may sometimes persist despite of effective blocking of the tubules. This may indicate that some other mechanisms may operate in the nerve activation instead of, or in addition to the hydrodynamic one. Inflammation may sensitize the nerve endings to such an extent that smaller fluid shifts would be sufficient for nerve activation or, for example, thermal stimulation may activate the nerves by a direct effect. On the other hand, spontaneously occurring changes in the exposed dentin, which in many cases seem to block the tubules may reduce the responses to hydrodynamic stimulation and, thus, have an opposite effect on dentin sensitivity. The results of animal experiments indicate that functional changes of this kind may occur. These results also indicate that real dentin hypersensitivity can develop as a result of inflammation induced sensitization of the nerves in the pulp-dentin border in teeth with open dentinal tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Role of intradental A- and C-type nerve fibres in dental pain mechanisms.

The arousal of the two components of pain (the first rapid or sharp pain and the second dull pain) are considered to be related to activation of A delta- and C-type nociceptive primary afferents, respectively. The same dichotomy of pain sensations may also exist in teeth, although due to the short distance between the site of stimulation and the brain the two sensations might not be as clearly separated as in stimulation of, for example, the extremities. The sensations evoked by stimulation of human teeth vary according to the type of the stimuli applied. Low-intensity electrical stimulation is able to induce non-painful (prepain) sensations. At high current intensities pain is evoked. Drilling, probing and air-drying of exposed dentin induce only pain. Most studies also indicate that thermal stimulation only induces painful sensations. The quality of dental pain can vary. Typically, dentinal stimulation of teeth with healthy pulps induces sharp pain. On the other hand intense heat stimulation can result in dull pain which radiates to a wider area of the face and jaws. This component of the stimulus-induced pain seems to share some characteristics of toothache associated with painful pulpitis. Single fibre recordings of intradental nerve activity in experimental animals have shown that in addition to A-fibres a considerable number of C-type primary afferents innervate the dental pulp. This is in accordance with the results of neuroanatomical studies, which indicate that 70-80% of pulpal axons in human, monkey, dog, and cat teeth are unmyelinated. Intradental A- and C-fibre groups seem to be functionally different and can be activated separately by certain external stimuli. Comparison of the response characteristics of the pulp nerve fibres and the sensations induced from human teeth indicate that: 1) A-fibres are responsible for the sensitivity of dentine and thus for the mediation of the sharp pain induced by dentinal stimulation, 2) Prepain sensations induced by electrical stimulation result from activation of the lowest threshold A-fibres some of which can be classified as A beta-fibres according to their conduction velocities. Comparison of the responses of the A beta- and A delta-fibres indicate that they belong to the same functional group, 3) Intradental C-fibres are activated only if the external stimuli reach the pulp proper. Their activation may contribute to the dull pain induced by intense thermal stimulation of the tooth and to that associated with pulpal inflammation.

Animals↗
PubMed1991

Relationship between craniomandibular dysfunction and pattern of speech sound production in a series of first-graders.

This report investigates associations between prevalence of functional disturbances of the masticatory system and speech disorders. The subjects were 157 children referred for speech therapy to the hospital and a control group all 130 first-graders at two elementary schools, mean age 7 years 6 months. During clinical examinations, signs and symptoms of TMJ dysfunction were recorded by the same dentist. Articulatory speech disorders were diagnosed by the same phoniatrician using the Remes Articulatory Test (Remes, 1975) for the Finnish language. The results showed that in the hospital referral group the mean value for maximal opening was smaller while laterotrusion movements and maximal protrusion of the mandible were larger than in the control group. The study group also more often had CM disorders and occlusal interferences than children of the first grade sample. In the present data, a higher frequency of subjective symptoms and several clinical signs of CMD were related to certain articulatory speech disorders. Risk of having too anteriorly-produced sounds, mainly 's'-sounds, decreased with advancing age in 6-8-year-old children. In conclusion, expression of both craniomandibular disorder and disorders in speech sound production seem to a considerable extent to reflect immaturity of fine motor control of the orofacial muscles in 6-8-year-old children.

Articulation Disorders↗
PubMed1990

The neurophysiology of the teeth.

Irritation of human teeth can evoke pain sensations of varying qualities depending on the type and intensity of the stimuli used. For example, drilling or air drying of dentin typically induces sharp, piercing pain, while intense heating of the tooth can cause dull, aching pain sensation. The dental pulp is richly innervated by both myelinated (A-fibers, mostly A delta-type) and unmyelinated (C-fibers) axons. A-fibers seem to be responsible for the sensitivity of dentin. They respond to stimuli that induce sharp pain in human teeth, for example, drilling of dentin and drying of dentin with air blasts. C-fibers are activated only when the stimuli used reach the pulp proper. They respond to intense heating. In human teeth, dull pain is induced at a temperature level corresponding to the heat thresholds of intradental C-fibers. The other functional characteristics of C-fibers indicate that they may play a role in the mediation of the dull pain connected with pulpal inflammation. Accordingly, activation of intradental nerve fibers of A- and C-type may contribute to the varying qualities of pain sensations induced by stimulation of human teeth.

Dental Pulp↗
PubMed1989

Reflex responses in the digastric and tongue muscles to stimulation of intradental nerves in the cat.

Electrical stimulation of tooth pulp nerves induces the digastric jaw-opening reflex in the cat, apparently due to activation of intradental A-fibres; C-fibres do not seem to be involved. In fact, reflex responses to activation of pulpal C-fibres have not been studied. In the present experiments on anesthetized cats we recorded EMG reflex responses of the digastric and tongue muscles to stimulation of the intact tooth crown, exposed dentine, and the pulp. We used stimuli that selectively activate either A- or C-fibres of the pulp. Slow heating of the tooth and application of capsaicin into the pulp, both procedures known to excite only C-fibres in the pulp, evoked licking movements of the tongue and prolonged EMG-responses in the tongue and, less consistently, digastric muscles. Similar muscle responses were elicited by high intensity electrical current pulses applied to the tooth. At low current intensities only short-duration digastric activation (jaw-opening reflex) was induced. Similar digastric jaw-opening was also evoked by drilling and air-drying of dentine, both stimuli able to activate only intradental A-fibres. These results indicate that activation of both A- and C-type pulp nerve fibres can induce reflectory muscle activation, and further, they support the concept of afferent intradental C-fibre innervation.

Animals↗
PubMed1989

Interaction between the autonomic and sensory nerves in the dental pulp.

The function of intradental sensory receptors is strongly affected by activation of the sympathetic nerves. This effect is most probably indirect and due to changes in pulpal blood flow. Also, in inflamed teeth the sensitivity changes of pulp nerves seem to be closely related to changes in the blood flow. Such inflammatory mediators as histamine, bradykinin and serotonin affect the sensitivity of intradental receptors in pulpal inflammation. In addition, many neuropeptides, for example substance P (SP) and calcitonin gene-related peptide (CGRP), seem to be involved and may interact with histamine or bradykinin. Recent studies indicate that intradental nerves with their neuropeptides may play a significant role in the inflammatory and defence reactions of the dental pulp.

Animals↗
PubMed1984

Excitation of tooth pulp afferents with electrical current.

Electrical excitation of tooth pulp afferents seems to be a most accurate and reproducable method to produce graded pain with minimal injury of the tissues. Besides electrical current only thermal stimulation may activate pulp nerves of an intact tooth, but this method lacks the precision of the electrical stimulation and bears more risk of injury. Surrounded by enamel of high resistance and capasitance the pulp nerves are difficult stimulation objects. On the other hand with careful stimulation the current is almost completely restricted to the pulp. The square wave current pulse is "deformed" according to the time constant of hard tissues and exceptionally long durations are needed. There is ultimate necessity for constant current stimulation because of varying anatomy and resistance of the teeth. When different amplitudes and durations of current pulses are used to compare perception thresholds of human teeth and firing thresholds of single pulp nerve fibres of the cat, it may be concluded that "prepain" sensation is experienced using current values that activate only A-fibres. To attain the pain threshold, recruitment of more A-delta fibres with increasing current is needed, but the lowest thresholds of C-fibres are even higher.

Animals↗
PubMed1984

The function of intradental nerves in relation to the sensations induced by dental stimulation.

Stimulation of intradental nerves has been widely used in pain research as a method for selective activation of pain pathways. It is believed that the only sensation experienced by human subjects in response to activation of pulp nerves is that of pain. However, this concept is not strictly correct. With electrical stimulation at threshold level or near to it a sensation which is not necessarily painful ("prepain") is experienced. When the stimulus intensity is increased suprathreshold, the sensation tends to change to a painful and unpleasant one. The changes in sensations are probably caused by activation of intradental nerve units with different thresholds and conduction velocities. In cats the fastest conducting pulp nerve fibres have the lowest thresholds and slowly conducting units are activated at much higher current levels. In most experiments on human teeth using natural stimuli like hot and cold the only sensation experienced has been pain. It seems also difficult for the subjects to find any difference between different stimuli. Correspondingly, in animal experiments it has been shown that different stimuli applied to dentine are capable of activating the same intradental nerve units probably with a common mechanism (hydrodynamic). However, some recent studies indicate that sensation of cold could be induced by stimulating human teeth.

Animals↗
PubMed1983

Intradental nerve activity induced by reduced pressure applied to exposed dentine in the cat.

In order to study the excitation of intradental nerves by fluid flow in dentinal tubules the following experiments were performed. The fluid flow was caused by reduced hydrostatic pressure applied to the exposed dentine surface of the canine teeth in the anesthetized cat. In one series of 7 cats the intradental nerve activity was recorded by means of electrodes inserted in dentinal cavities. Provided that the pressure was sufficiently reduced and applied to acid-etched dentine in preparations of sufficient depth, intradental nerve activity of different impulse amplitudes was recorded. The responding pressure sensitive units were found to be sensitized by a brief local application of veratrine and desensitized by potassium chloride. In the second series 26 single functional pulp nerve fibre units were dissected from the inferior alveolar nerve in 7 cats. Nerve impulses were recorded by means of platinum-iridium wire electrodes. The conduction velocities of the 9 fibres responding to reduced pressure varied from 8.3 to 43.0 m/s. Five of these fibres also responded to elevated pressure. None of the 9 fibres conducting impulses with a velocity below 2 m/s responded to a reduction in pressure. thus, the present data strongly suggest that intradental nerve endings with myelinated axons are activated by fluid flow in dentinal tubules. Our results support the hydrodynamic mechanism of dentine sensitivity.

Acid Etching, Dental↗
PubMed1983

Thresholds of intradental A- and C-nerve fibres in the cat to electrical current pulses of different duration.

Electrical current pulses of quite variable duration have been used in activation of intradental nerves both in human subjects and experimental animals. It seems, however, that little information is available about the effect of pulse duration on the responses of single pulp nerve units. The aim of the present study was to investigate the effect of pulse duration on excitation thresholds of intradental A- and C-fibres in the cat. In 12 anesthetized cats 61 C- and 53 A-nerve units were identified and recorded. Electrical thresholds were determined with current pulses of different duration from 0.2 to 50.0 ms. The maximal stimulus intensity was 200 microA. Conduction velocities of all recorded units and absolute refractory periods of 20 A- and 20 C-units were determined. Intradental A- and C-fibres had different strength-duration properties. with all pulse durations A-fibres had the lowest thresholds. Part of the C-fibres did not respond to the shortest current pulses even with the maximum stimulus intensity (200 microA). with 0.2 ms pulses only 31.1% of the recorded C-fibres could be activated. In some A-fibres a single current pulse of long duration was capable of inducing several action potentials, when the stimulus intensity was increased suprathreshold. Refractory periods of A-units were less than 2.0 ms and those of C-units 5.0-9.0 ms. It is concluded that in electrical stimulation of teeth duration of current pulses strongly affects responses of single intradental fibre units.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗