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Biomedical subjects

A Pertovaara

Publications and source records attributed to A Pertovaara.

At least 73 records · Page 4Linked to original sources
PubMed1994

The movement-induced modulation in discriminability between cutaneous nonpainful stimuli depends on test stimulus intensity.

The purpose of this study was to find out whether the finger movement-induced modulation of cutaneous discrimination thresholds varies with the intensity level of the test stimulation in various movement conditions. The effect of active and passive finger movement on cutaneous sensitivity to nonpainful electrical stimulation of threshold and suprathreshold intensity was studied in human subjects. The detection threshold and the just-noticeable amplitude difference (discrimination threshold) at two suprathreshold intensities (3 x and 10 x detection threshold) were determined using a forced-choice paradigm before and after (controls) or during finger movement. In one condition the stimuli were applied just prior to the movement. The finger was actively or passively moved at the frequency of 1.5 Hz or 3 Hz, and the test stimuli were applied to the moving finger, except in one condition to the contralateral finger. The contralateral condition was used to rule out vigilance- and attention-related mechanisms as a cause of sensitivity changes. Active as well as passive movement of the finger produced a significant increase in the detection threshold during the movement. Also just prior to the movement the detection threshold was increased. Suprathreshold discrimination thresholds in the moving finger were not significantly changed during or just prior to the active movement, whereas during passive movement the discrimination threshold to suprathreshold level stimulation was significantly decreased. When test stimuli were applied to the finger contralateral to the actively moving finger, neither the detection threshold nor the discrimination between stimuli of suprathreshold intensities were significantly changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A selective suppression of human pain sensitivity by carbon dioxide: central mechanisms implicated.

The effect of breathing CO2 on somatic sensitivity was studied in human subjects. Healthy humans breathed room air, 100% O2, or CO2 (5% or 8% in O2). Thresholds to heat pain, mechanical pain, electrically evoked pain, and electrically evoked perception were measured using psychophysical techniques. Also, the effects on sensory and affective components of experimental ischaemic pain, alertness and on cardiovascular parameters were observed. In addition, the effect of CO2 on heat pain threshold was determined in the ischaemic limb to exclude the possibility that the threshold elevation was due to an action on primary afferent fibres. Naloxone (0.8 mg), dexamethasone (0.1 mg) or placebo (0.9% NaCl) were applied intravenously in double blind tests to reverse the threshold elevations. In an electrophysiological experiment the effect of CO2 on a spinal nociceptive flexion reflex evoked by an electric stimulus was measured. The CO2 produced a dose-dependent elevation of the heat pain threshold. Similarly, the sensory and affective components of experimental ischaemic pain were attenuated by CO2. The heat pain threshold was significantly elevated by CO2 in the ischaemic limb, also. However, there was no effect on thresholds to mechanically or electrically induced pain or perception thresholds to electrically evoked sensations. One hundred percent O, did not elevate the heat pain threshold. In double blind tests the heat pain threshold elevation was not significant when the naloxone or dexamethasone was administered. The threshold to electrically evoked spinal flexion reflex was not elevated by CO2. The CO2 at the current dose produced sedation, an increase in blood pressure but no change in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Blood flow increase in the orofacial area of humans induced by painful stimulation.

The purpose of this study was to investigate if painful stimulation produces blood flow changes in the tooth pulp and the facial skin in humans. Also, we attempted to find out if the possible blood flow changes induced by painful stimulation could be explained by central sympathetic and parasympathetic reflex mechanisms, by an antidromic activation of nociceptive axons (axon reflex), or by a change in central cardiovascular parameters. Laser Doppler flowmeter was used to assess the blood flow changes. Electrical tooth pulp stimulation at painful intensities induced a blood flow increase in the ipsilateral lip adjacent to the stimulus site, and vice versa. Nonpainful stimulation had no effects. Painful thermal stimulation of the upper lip also produced an increase in the blood flow of the ipsilateral upper incisor. The blood flow changes in the lip produced by dental stimulation were not correlated with changes in systemic blood pressure or heart rate. Painful electrical stimulation of the hand did not induce any changes in the pulpal blood flow, whereas painful dental stimulation produced a blood flow decrease in the finger but no change in the contralateral lip or cheek. In monkey experiments a regional block of the central conduction of the inferior alveolar nerve at the level of the mandibular foramen produced varying results: the blood flow increase in the lower incisor produced by noxious thermal stimulation of the ipsilateral lower lip was not abolished in two experiments but was abolished in other two experiments. It is concluded that painful stimulation can induce significant increases in the blood flow of the orofacial regions in humans. This increase is predominantly restricted to the region adjacent to the stimulus site and cannot be explained by changes in the central cardiovascular parameters. Central neuronal reflex mechanisms and an axon reflex may both underlie these blood flow increases.

Adult↗
PubMed1994

Spinal potentiation and supraspinal additivity in the antinociceptive interaction between systemically administered alpha 2-adrenoceptor agonist and cocaine in the rat.

We studied the antinociceptive interaction of systemically administered medetomidine, a selective alpha 2-adrenoceptor agonist, with cocaine in the tailflick and hotplate tests in rats. In intact rats, both medetomidine alone (25-300 micrograms/kg subcutaneously [SC]) and cocaine alone (10-30 mg/kg intraperitoneally [IP]) produced a dose-dependent antinociception in the supraspinally mediated hotplate test, and their combination (medetomidine 25 micrograms/kg+cocaine 10-20 mg/kg) produced an additive antinociceptive effect. In the spinally mediated tailflick test, only medetomidine alone produced a significant antinociceptive effect both in intact and spinal rats, whereas cocaine alone produced a marginally significant antinociceptive effect in the tailflick test only at the highest dose used (30 mg/kg) and only in intact rats. The combination of medetomidine (25 micrograms/kg SC) with cocaine (10-20 mg/kg IP) produced potentiation of antinociception in the tailflick test both in intact and spinal rats. The results indicate that at the supraspinal level there is an additive antinociceptive interaction between cocaine and medetomidine, whereas at the spinal level cocaine potentiates the medetomidine-induced antinociception independent of supraspinal mechanisms. The results further support previous evidence indicating that antinociception produced by a systemically administered alpha 2-adrenergic drug alone is mainly due to spinal mechanisms, whereas that by systemically administered cocaine alone is mainly due to supraspinal mechanisms.

Adrenergic alpha-Agonists↗
PubMed1993

Capsaicin-induced central facilitation of a nociceptive flexion reflex in humans.

The effect of selective activation of nociceptive primary afferent fibers by capsaicin on a nociceptive lower limb flexion reflex was studied in healthy human subjects. Capsaicin (1%) applied topically to the skin produced a burning spontaneous pain sensation and allodynia in the treated region and in its immediate vicinity. Capsaicin applied to the distal innervation area of the sural or saphenous nerve produced a significant decrease of the threshold for the nociceptive limb flexion reflex induced by electric stimulation of the proximal sural nerve trunk, and this threshold decrease was rapidly attenuated by a cool compress concomitantly with the attenuation of the capsaicin-induced spontaneous pain. The latency of the flexion reflex response was not changed by capsaicin. The non-nociceptive H-reflex was not modified by capsaicin. It is concluded that a selective activation of nociceptive primary afferent fibers of the skin by capsaicin produces a central facilitation of a nociceptive flexion reflex in humans. This facilitation is selective on the nociceptive reflex and depends, at least partly, on the on-going afferent barrage in C-fibers.

Administration, Topical↗
PubMed1993

Influence of an experimental peripheral mononeuropathy on the responses of medial bulboreticular neurons to noxious skin stimulation and the modulation of the responses by an alpha 2-adrenoceptor agonist in the rat.

A peripheral mononeuropathy was induced in rats by the placement of four loose ligatures around the right sciatic nerve. After the development of mechanical hyperalgesia in the neuropathic limb, the responses of medial bulboreticular neurons to noxious skin stimulation were determined, and the attenuation of the responses was attempted by administering systemically medetomidine, a highly specific alpha 2-adrenoceptor agonist. The neuronal responses to noxious stimulation of the sciatic nerve area or the saphenous nerve area in the hyperalgesic limb were of a magnitude equal to that of the responses from the corresponding areas in the intact limb of neuropathic or control rats. Also the spontaneous activity of bulboreticular neurons in neuropathic rats was of a magnitude equal to that in intact rats. The dose-dependent (50-200 micrograms/kg) suppression of the evoked responses by medetomidine was equal in intact and neuropathic animals. It is concluded that the medial bulboreticular neurons are not involved in the development of hyperalgesia in rats with an experimental mononeuropathy.

Adrenergic alpha-Agonists↗
PubMed1993

Effects of jaw clenching, jaw movement and static jaw position on facial skin sensitivity to non-painful electrical stimulation in man.

The effects of isometric jaw clenching, static jaw position and jaw movement on electrically evoked perception thresholds of the facial skin of the mental region were studied in healthy human subjects. Exercise consisted of brief (1 s) isometric contractions of jaw-closing muscles against a static load (30% of the maximum force), or continuous jaw movements at two different frequencies (1 and 3 Hz). A visual cue was used to indicate the start and end of the isometric exercise (duration 1 s.). Isometric jaw clenching induced a significant elevation of perception thresholds in the skin of the lower jaw just before and during the early electromyographic response of the jaw-closing muscles. This elevation was attenuated before the end of the exercise. Corresponding thresholds evoked by electrical stimulation applied to the dorsum of the hand were not changed by isometric jaw clenching. Changes in static jaw position did not have any effect on detection thresholds. Continuous 'masticatory-like' jaw movements produced a velocity-dependent reduction of sensitivity in the facial skin. The suppression was significantly stronger than that produced by isometric jaw exercise. An imagined isometric biting exercise, which presumably activated the supplementary motor cortex, did not cause any threshold elevations. The results indicate that isometric jaw clenching as well as cyclical jaw movements produce segmentally a phasic, rapidly attenuating masking of facial skin sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The rostroventromedial medulla is not involved in alpha 2-adrenoceptor-mediated antinociception in the rat.

The aim of the current study was to investigate the role of the rostroventromedial medulla (RVM) in alpha 2-adrenoceptor-mediated antinociception. Medetomidine or clonidine, selective alpha 2-adrenoceptor agonists were microinjected into the RVM in unanesthetized rats with a chronic guide cannula. The antinociceptive effects were evaluated using the tail-flick and hot-plate tests. For comparison, medetomidine was microinjected into the cerebellum or the periaqueductal gray (PAG). To study the role of medullospinal pathways, the tail-flick latencies were also measured in spinalized rats. The reversal of the antinociception induced by intracerebral microinjections of medetomidine was attempted by s.c. atipamezole, a selective alpha 2-adrenoceptor antagonist. The reversal of the antinociception induced by systemic administration of medetomidine was attempted by microinjections of 5% lidocaine or atipamezole into the RVM. When administered into the RVM, medetomidine produced a dose-dependent (1-30 micrograms) antinociception in the tail-flick and hot-plate tests, which antinociceptive effect was completely reversed by atipamezole (1 mg/kg, s.c.). Also clonidine produced a dose-dependent (3-30 micrograms) antinociception following microinjection into the RVM. Microinjections of medetomidine into the cerebellum or the PAG produced an identical dose-response curve in the tail-flick test as that obtained following microinjection into the RVM. In spinalized rats the antinociceptive effect (tail-flick test) induced by medetomidine microinjected into the RVM was not less effective than in intact rats. Lidocaine (5%) or atipamezole (5 micrograms) microinjected into the RVM did not attenuate the antinociception induced by systemically administered medetomidine (100 micrograms/kg, s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Antinociception induced by alpha-2-adrenoceptor agonists, with special emphasis on medetomidine studies.

Alpha-2-adrenoceptor agonists can activate varying antinociceptive mechanisms depending on the dose and the route of administration, although the main site for their antinociceptive effect in physiological pain conditions seems to be the spinal dorsal horn. In this paper the investigations on the underlying mechanisms are reviewed, with particular emphasis on novel studies using a highly selective and potent alpha-2-adrenoceptor agonist medetomidine. In behavioral studies alpha-2-adrenoceptor agonists, including medetomidine, produce antinociception following systemic administration or local application to the spinal cord. Following systemic administrations the antinociceptive effect at subanesthetic doses in physiological pain conditions is weak and the affective-motivational component of pain is more sensitive to suppression than sensory-discriminative aspect of pain. Electrophysiological studies at the spinal cord level indicate that alpha-2-adrenoceptor agonists suppress the responses of the pain-relay neurons both due to pre- and postsynaptic spinal cord level mechanisms following systemic or intrathecal drug administration. The antinociceptive effect at the spinal cord level is selective, since non-nociceptive signals are not attenuated. According to electrophysiological single neuron recordings, nociceptive signals at supraspinal levels are more sensitive to antinociceptive effects of systemically administered alpha-2-adrenoceptor agonists than nociceptive signals at the spinal cord level. However, according to immunocytochemical imaging of immediate early gene response to noxious stimulation, medetomidine strongly suppresses responses at the spinal cord level already following a systemic dose (100 micrograms/kg i.p.) which is not enough to produce a significant suppression of spinally-initiated nocifensive tail reflexes nor the electrophysiologically recorded responses to nociceptive spinal neurons. Thus, the higher sensitivity of supraspinal neuronal responses and their behavioral correlates to the antinoceptive effect of medetomidine obviously reflects the cumulative effect of medetomidine at several areas along the polysynaptic pathway to the rostral parts of the brain. Paradoxically, the response of immediate early genes in the medial thalamic neurons is only slightly, influenced by antinociceptive doses of medetomidine. Alpha-2-adrenoceptors have significant interactions with other receptors (e.g. opioid, serotonin and muscarine) in producing antinociception at the spinal cord level.

Adrenergic alpha-Agonists↗
PubMed1993

Induction and suppression of immediate-early genes in the rat brain by a selective alpha-2-adrenoceptor agonist and antagonist following noxious peripheral stimulation.

The effect of medetomidine, a highly selective alpha-2-adrenoceptor agonist, on noxious stimulation-induced expression of immediate-early genes was studied in the central nervous system of the rat. The expressions of c-JUN, JUN B, c-FOS FOS B and KROX-24 proteins were investigated by immunocytochemistry following the application of formalin (5%, 50 microliters) into the plantar skin of one hindpaw. Medetomidine (100 or 300 micrograms/kg i.p.) was administered 12 min or 5 min before the application of formalin. Atipamezole (1.5 mg/kg i.p.), and alpha-2-adrenoceptor antagonist, administered simultaneously with medetomidine (300 micrograms/kg), was used to reverse the alpha-2-adrenergic effects. The rats were killed and perfused 90 min after formalin injection. Formalin induced expression of all studied proteins in the ipsilateral spinal dorsal horn and the contralateral parabrachial nucleus, and in the medial thalamus bilaterally. Both medetomidine doses administered 12 min before formalin strongly suppressed the expression of c-FOS in the spinal dorsal horn; the suppression was stronger in the deep (III-VI) than in the superficial (I and II) laminae of the dorsal horn (76% and 86% for 100 micrograms/kg dose vs 97% and 99% for 300 micrograms/kg dose, respectively). However, application of medetomidine 5 min before formalin did not reduce the expression of immediate-early genes. In the parabrachial nucleus, both medetomidine doses also produced a significant suppression of c-FOS expression (68%). In contrast, medetomidine at the dose of 100 micrograms/kg was ineffective in the medical thalamus. Only the higher dose of medetomidine (300 micrograms/kg) produced a suppression by 29% and 46% in centromedian and paraventricular nuclei, respectively. Atipamezole produced a significant attenuation in spinal cord and a complete reversal in parabrachial nucleus of the medetomidine-induced suppression. However, in the medial thalamus, atipamezole produced a dramatic increase of formalin-induced c-FOS expression when compared with formalin injection alone. The expression of c-JUN, JUN B, FOS B and KROX-24 proteins paralleled that of c-FOS. It is concluded that the expression of immediate-early gene encoded proteins is more strongly suppressed by alpha-2-adrenoceptor agonists in spinal and parabrachial than in medial thalamic neurons. The increased expression of immediate-early genes in medical thalamus following atipamezole treatment may be explained by increased release of noradrenaline and the consequent activation of alpha-1- and beta-adrenoceptors. Compared with the previously reported effects of behaviorally equipotent doses of morphine, the suppression of c-FOS expression in the spinal cord was stronger following medetomidine than that following morphine.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Agonists↗
PubMed1992

Lowered cutaneous sensitivity to nonpainful electrical stimulation during isometric exercise in humans.

The effect of isometric exercise on cutaneous sensitivity to nonpainful electric stimulation was studied in human subjects. The exercises consisted of brief (duration: 1-10 s) palmar flexions of the hand or foot against varying loads (10-30% of the maximal force). A visual "go" cue was used to indicate the start and end of the exercise. Isometric hand exercise produced a load-dependent increase of electrotactile thresholds of the fingers. The threshold elevation was rapidly attenuated with prolonged duration of the exercise. The hand exercise-induced threshold elevation was of equal magnitude in the glabrous and hairy skin of the fingers. Thresholds were not changed for the hand contralateral to the exercising hand. Passive static pressure of the hand did not produce threshold changes, whereas activation of afferent inhibition by a vibrotactile stimulus (100 Hz, 0.1 mm) did produce a significant threshold elevation. Exercise-induced threshold elevation was also significant immediately prior to the EMG response of the arm but not at the time of the visual "go" signal, or before it. The threshold increase found during the EMG response was not significantly stronger than that found prior to the EMG response. These results suggest that isometric exercise load-dependently produces a phasic, rapidly attenuating increase in cutaneous tactile thresholds in the exercising limb but not multisegmentally. Corollary efferent barrage from motor to sensory structures of the brain could be underlying the threshold changes produced by isometric exercise, whereas afferent inhibitory mechanisms seem to have only a minor role.

Adult↗
PubMed1992

Increased sexual behavior in male Macaca arctoides monkeys produced by atipamezole, a selective alpha 2-adrenoceptor antagonist.

The effect of a highly selective and potent alpha 2-adrenoceptor antagonist, atipamezole, on sexual behavior was studied in three stumptail macaques (Macaca arctoides). Following IM administration of atipamezole or saline control, the behavior of the male monkey with a female monkey was observed for 30 min. Atipamezole dose dependently (0.01-0.15 or 0.30 mg/kg) produced a significant increase in the number of ejaculations in all three monkeys, including an old one with decreased sexual activity in control conditions. Both ejaculations obtained by copulation and masturbation were increased. It is concluded that atipamezole is effective in increasing sexual behavior in male stumptail monkeys.

Adrenergic alpha-Antagonists↗
PubMed1992

Effects of medetomidine, an alpha-2 adrenoceptor agonist, and atipamezole, an alpha-2 antagonist, on spatial memory performance in adult and aged rats.

The effects of a novel, highly selective alpha-2 agonist, medetomidine, and its antagonist, atipamezole, were studied on the working memory of rats performing a spatial delayed alternation task. Testing was performed in two stages, at the age of 8.3 months (mean) and again when the rats were 17.6 months (mean). A low dose (3 micrograms/kg) and a high dose (30 micrograms/kg) of medetomidine improved the performance of the old rats in the memory task but had no effect on the young rats. The dose-response curve of medetomidine resembles that of guanfacine, another alpha-2 agonist. At the low dose of medetomidine (3 micrograms/kg) the animals showed no signs of sedation. Since medetomidine even at a low dose has a beneficial effect on the memory performance of old rats, it could be a good candidate for the treatment of age-associated memory dysfunction.

Adrenergic alpha-Agonists↗
PubMed1992

Enhancement of morphine-induced analgesia and attenuation of morphine-induced side-effects by cocaine in rats.

Effect of cocaine on morphine-induced analgesia and the accompanying respiratory depression, bradycardia and hypolocomotion/sedation was studied in rats. Cardiovascular and respiratory effects were studied under pentobarbitone-induced anaesthesia. Cocaine enhanced morphine-induced analgesia in the formalin test, hot plate test and heat-induced tail withdrawal test in intact rats. However, in spinal rats a similar combination of cocaine with morphine did not produce increased latencies in the tail withdrawal test. Of the three analgesic tests used, the formalin test was the most sensitive to the enhancement, as well as to the effects of morphine or cocaine alone. Morphine at the dose of 6 mg/kg produced complete analgesia in the formalin test, significant hypolocomotion/sedation, significant bradycardia and significant decrease in the respiratory rate. At an equianalgesic dose (complete analgesia in the formalin test) of morphine (3 mg/kg)-cocaine (5 mg/kg)-combination no significant changes in heart rate, respiratory rate or locomotion(/alertness) were observed. Changes in skin blood flow determined by the laser Doppler flow method were not significant in any of the experimental conditions. The results indicate that cocaine enhances morphine-induced analgesia, mainly due to supraspinal mechanisms. In contrast, the morphine-induced bradypnoea, bradycardia and hypolocomotion/sedation are attenuated by cocaine.

Analgesia↗
PubMed1992

Response characteristics of tooth pulp-driven postsynaptic neurons in the spinal trigeminal subnucleus oralis of the cat.

Neuronal activity in the spinal trigeminal subnucleus oralis in response to electrical tooth stimulation was recorded in the anaesthetized cat in order to compare the electrophysiological characteristics of the oralis neurons with those of subnucleus caudalis and interpolaris neurons recorded in previous studies. The most sensitive oralis neurons had lower thresholds and shorter latencies than the most sensitive caudalis and interpolaris neurons. The thresholds of the oralis neurons were lower and their strength-duration curves flatter than those depicting liminal dental pain in man but similar to those depicting liminal jaw reflexes in the cat. Noxious conditioning stimulus elevated the threshold of only 1 of 10 neurons tested. The converging input from the skin and oral mucosa was from low-threshold mechanoreceptors. The results indicate that the response properties of the subnucleus oralis neurons differ significantly from those of other spinal subnuclei. Human pain thresholds cannot be explained by the liminal response properties of oralis neurons. These neurons might be important in the mediation of liminal reflex events evoked by dental stimuli.

Animals↗
PubMed1992

Effects of atipamezole, an alpha 2-adrenoceptor antagonist, on the anesthesia induced by barbiturates and medetomidine.

We studied the effects of atipamezole, an alpha 2-adrenoceptor antagonist, on hypnosis induced by medetomidine, an alpha 2-adrenoceptor agonist (1 mg/kg IP), and pentobarbital (40 mg/kg IP) by testing the righting reflex in the rat. The duration of antinociception was assessed with repeated pinch tests. Medetomidine-induced hypnosis and antinociception were inhibited by atipamezole at doses greater than 0.1 mg/kg. Atipamezole restored the righting reflex at a dose ratio that was 1:10 or more to that of medetomidine used to induce hypnosis. Subcutaneous atipamezole (1.5 mg/kg) increased the duration of hypnosis induced by pentobarbital (40 mg/kg) and pentobarbital + medetomidine (0.3 mg/kg). Hypnosis induced by methohexital (60 mg/kg IP) was also prolonged by atipamezole. The capacity of atipamezole to reverse the effects of medetomidine is also reduced in the presence of barbiturates. Thus, atipamezole should be used only at low doses to reverse a combination anesthesia induced by barbiturates and medetomidine.

Adrenergic alpha-Antagonists↗