Biomedical subjects

A Pertovaara

Publications and source records attributed to A Pertovaara.

At least 91 records · Page 5Linked to original sources

PubMed1991

Antinociception in bulboreticular neurons of the rat produced by spinally administered medetomidine, an alpha 2-adrenoceptor agonist.

The aim of this investigation was to evaluate if spinal alpha 2-adrenergic mechanisms modulate the nociceptive input to the medial bulboreticular formation. The effect of intrathecal (i.t.) medetomidine, a highly selective alpha 2-adrenoceptor agonist, was studied on peripherally evoked stimulation of the nociceptive bulboreticular formation neurons of the rat. The response to stimulation of the hind- and forepaw was evaluated separately in the same neurons before and after i.t. application of medetomidine from the catheter located at the lumbar level. Medetomidine i.t. produced a dose-dependent (2.5-7.5 micrograms) suppression of the nociceptive responses, and this suppression was completely reversed by i.p. atipamezole (1.5 mg/kg), a highly selective alpha 2-adrenoceptor antagonist. The average i.t. dose of medetomidine needed to produce 50% suppression was 2.2 micrograms for the hindpaw-elicited responses and 4.5 micrograms for the forepaw-elicited responses. Maximal suppression was obtained within 10 min and lasted for at least 60 min. When applied systemically (i.p.), much higher doses of medetomidine were needed for suppression of responses to the neuronal population studied (155 micrograms/kg of medetomidine needed to produce a 50% suppression of the evoked response). The results suggest that medetomidine can significantly attenuate nociceptive input to the medial bulboreticular formation due to spinal alpha 2-adrenergic mechanisms.

Adrenergic alpha-Agonists↗

PubMed1991

Attempted reversal of cocaine-induced antinociceptive effects with naloxone, an opioid antagonist.

We attempted to reverse the behavioral and neuronal antinociceptive effects of cocaine with naloxone, an opioid antagonist. Cocaine (20 mg/kg i.p.) produced a strong analgesic effect in the formalin test and in the tail pinch test. These cocaine-induced analgesic effects could be reversed by naloxone at a very high dose (10 mg/kg) but not at a dose (1 mg/kg) which was sufficient to attenuate morphine (10 mg/kg)-induced analgesia. Naloxone alone at a dose of 10 mg/kg did not produce significant effects. In general, nociceptively evoked responses in medial thalamic neurons were suppressed by cocaine (20 mg/kg), and this suppression was attenuated by naloxone (10 mg/kg). The results suggest that opioid receptors which are not involved in mediating morphine-induced analgesia and which have a low sensitivity to naloxone are involved in cocaine-induced central analgesia.

Analgesics↗

PubMed1991

Modulation of skin sensitivity by dynamic and isometric exercise in man.

The effect of dynamic cycle ergometer exercise and isometric leg exercise on skin sensitivity was studied in man. Exercise was performed at different loads. Cutaneous sensitivity to innocuous and noxious thermal stimuli was tested using a contact thermostimulator and sensitivity to tactile stimuli was tested using electrical stimuli. During isometric exercise a segmental (the exercising limb), but not a multisegmental, phasic decrease of cutaneous thermal sensitivity to innocuous stimuli was found. At the isometric forces used the effect on tactile and heat pain sensitivity was not significant. During dynamic exercise a multisegmental, load-dependent decrease of sensitivity in all tested sensory modalities was found and this attenuation disappeared gradually after the end of exercise. In contrast to isometric exercise, the decrease of sensitivity produced by dynamic exercise was most evident in tactile sensitivity. The size of the stimulus area (7.9 vs 11.8 cm2) did not have a significant effect on the magnitude of the exercise-induced decrease of cutaneous thermal sensitivity to innocuous stimuli. It was concluded that underlying the modulation of skin sensitivity by dynamic and isometric exercise were mechanisms that were different, at least to a small extent. Isometric exercise produced a segmental modulation of skin sensitivity due to central neuronal mechanisms, independent of exercise-induced stress. Exercise-induced stress could have caused the modulation of skin sensitivity by dynamic exercise.

Adult↗

PubMed1991

Effects of different sensory and behavioral manipulations on autotomy caused by a sciatic lesion in rats.

We studied the effects of different sensory and behavioral manipulations on autotomy (self-mutilation). Lidocaine and bupivacaine pretreatments of the transected nerves delayed the onset of autotomy. Short prelesional stimulation (crush) of the transected nerve did not enhance autotomy significantly. Daily handling decreased autotomy behavior strongly and a visual cue placed on the denervated skin increased autotomy slightly. The delayed onset of the autotomy behavior after locally administered anesthetics suggests that the lesion-induced afferent barrage modified self-mutilation. The decreased self-mutilation after daily handling could be a consequence of handling stress. The increase of autotomy after the visual cue might have resulted from the attention-induced increase of the activity in ascending nociceptive tracts.

Afferent Pathways↗

PubMed1991

The effects of medetomidine, an alpha-2-adrenoceptor agonist, and cocaine on the tooth pulp-evoked jaw-opening reflex in cat.

In the pentobarbitone-anesthetized cat, the threshold of the tooth pulp-elicited jaw-opening reflex was elevated in a dose-dependent way (30-100 micrograms/kg, IP) following the administration of medetomidine, an alpha-2-adrenoceptor agonist. This elevation was significantly reduced by atipamezole (1 mg/kg, IP), an alpha-2-adrenoceptor antagonist. The inhibitory interaction between two successive dental stimuli applied to the same tooth (in-field inhibition) was suppressed by a lower dose of medetomidine (30 micrograms/kg) than the threshold elevation to single electrical pulses (55 micrograms/kg). Only the highest dose of medetomidine used (100 micrograms/kg) significantly influenced the temporally facilitated (in-field facilitation) response. In comparison, cocaine, a nonspecific monoaminergic agent, did not produce a significant threshold elevation of the tooth pulp-elicited jaw-opening reflex (1-25 mg/kg, IP). It is concluded that medetomidine, through an action on alpha-2-adrenoceptors, can suppress a predominantly nociceptive trigeminal reflex in anesthetized cats. The threshold evoked by single electric pulses, in-field inhibition, and in-field facilitation display differential sensitivities to medetomidine effects.

Adrenergic alpha-Agonists↗

PubMed1991

Involvement of supraspinal and spinal segmental alpha-2-adrenergic mechanisms in the medetomidine-induced antinociception.

The effect of systemically administered medetomidine, a selective alpha-2-adrenoceptor agonist, was studied by electrophysiological recordings of the peripherally evoked responses of three different types of sensory neuronal populations in the rat: medial thalamic neurons exclusively responding to mechanical cutaneous stimuli at noxious intensities, spinothalamic tract neurons of the spinal cord responding exclusively or differentially to mechanical cutaneous stimuli at noxious intensities, and low-threshold mechanoreceptive spinal dorsal horn neurons with ascending projections. The neuronal effects were compared with the behavioral data obtained in mechanically and thermally induced nociceptive tail reflex tests in intact and spinal rats. A reversal of the antinociceptive effects was attempted by systemically (1.5 mg/kg, i.p.) or intrathecally (25 micrograms) administered atipamezole, a selective alpha-2-adrenoceptor antagonist. Systemically administered medetomidine produced an atipamezole-reversible, dose-dependent suppressive effect on the evoked responses of nociceptive medial thalamic and spinothalamic tract neurons. A lower dose of medetomidine was needed to suppress significantly (half-maximally) evoked responses of the nociceptive medial thalamic neurons (100 micrograms/kg) than those of the nociceptive spinothalamic tract neurons (300 micrograms/kg). The decrease of evoked responses of the nociceptive spinothalamic tract neurons was accompanied by a decrease in spontaneous activity. The responses of the low-threshold mechanoreceptive projection neurons of the spinal cord were not influenced by medetomidine (30-300 micrograms/kg). The reflex studies with a (anesthetic) medetomidine dose of 300 micrograms/kg indicated that in intact and otherwise drug-free rats, medetomidine produced a significant prolongation of the nociceptive reflex response latency to a tail-pinch and heat; these antinociceptive effects of systemic medetomidine were reversed by systemically and intrathecally applied atipamezole. In spinal rats systemically applied medetomidine (300 micrograms/kg) also produced a significant prolongation of the tail-flick latency, which was reversed by systemically applied atipamezole. The results suggest that a high anesthetic dose of systemically applied medetomidine (300 micrograms/kg) can suppress nociceptive sensory neuronal and reflex responses due to spinal segmental mechanisms through an action on alpha-2-adrenoceptors. This spinal effect is selective to responses of nociceptive neurons, and at least partly postsynaptic as indicated by the concomitant decrease in spontaneous activity. At a lower, subanesthetic (but sedative) dose (100 micrograms/kg) the antinociceptive effect of systemically applied medetomidine can be explained by supraspinal alpha-2-adrenergic mechanisms.

Adrenergic alpha-Agonists↗

PubMed1991

Effect of systemic medetomidine, an alpha 2 adrenoceptor agonist, on experimental pain in humans.

The effect of systemic (intravenous) medetomidine, an alpha-2 adrenoceptor agonist, on pain thresholds was studied in healthy human subjects (n = 6). Medetomidine produced a dose-dependent (cumulative doses: 25 and 50 micrograms) sedative effect evaluated by visual analog scale. Also, a dose-dependent decrease of blood pressure but not of heart rate was seen after administration of medetomidine. Pain threshold to electric stimulation of the tooth pulp and cutaneous heat pain threshold were uninfluenced by medetomidine. An index of cutaneous thermal sensitivity to innocuous stimuli, the width of the thermoneutral zone, also was uninfluenced by medetomidine. Medetomidine produced a significant attenuation of the affective-motivational component (unpleasantness) of tourniquet-induced ischemic pain, whereas the sensory-discriminative component (pain magnitude estimate) of the ischemic pain was not attenuated. The results suggest that systemic medetomidine alone at subanesthetic but sedative and hypotensive doses does not significantly influence the intensity and thresholds of experimental pain, whereas the affective-motivational component of pain can be attenuated.

Adrenergic alpha-Agonists↗

PubMed1991

An attempted reversal of cocaine-induced analgesia by dexamethasone.

Analgesia produced by systemic cocaine (20 mg/kg intraperitoneally) was not attenuated by dexamethasone (0.25-2.5 mg/kg) in the formalin or tail pinch test in rats. The result suggests that the activation of the corticotropin releasing factor-adrenocorticotropin/beta-endorphin axis does not explain cocaine-induced analgesia.

Analgesics↗

PubMed1990

The effect of systemic cocaine on the responses to noxious stimuli and spontaneous activity of medial bulboreticular projection neurons.

The effect of antinociceptive doses of cocaine (25 mg/kg, i.p.) on unit responses to noxious somatic stimuli and spontaneous activity of antidromically identified projection neurons in the medial medullary reticular formation (MRF) was studied in the rat. Thirty-three antidromically activated neurons were recorded from the medullary raphe, gigantocellular, or paragigantocellular nuclei in an acute anaesthetized preparation; 25 cells projected to the spinal cord and 8 neurons had rostral projections through the medial forebrain bundle (n = 4) or the medial thalamus (n = 4). After cocaine administration, 24 (73%) of these cells showed immediate (less than 5 min) and prolonged (45-70 min) increases in their level of spontaneous activity. Associated with this increased interstimulus activity, 21 of 29 (72%) neurons responsive to noxious somatic stimulation reduced their responsiveness, relative to prestimulus activity, after cocaine administration. In 5 animals tested, the cocaine-induced changes in spontaneous activity and changes in evoked responsiveness were unaffected by naloxone (1 mg/kg, i.p.) but partially reversed within 5 min of the administration of chlorpromazine (3 mg/kg, i.p.). There were no obvious differences in neuronal response characteristics or the effect of cocaine that correlated with anatomical location or direction of axonal projection. Similar results were obtained while recording from 14 somatically responsive units in chronic, unrestrained, lightly anesthetized or awake rats. These findings provide direct evidence that cocaine, in doses that are antinociceptive for the rat, affects both unit responses to noxious stimuli and the spontaneous activity of caudally and rostrally projecting bulboreticular neurons over a time course that parallels the behavioral antinociception. The observation that unit responses to somatic stimuli were reduced while spontaneous activity was unchanged or increased in most cells suggests that cocaine antinociception may be due to the activation of sensory inhibitory mechanisms mediated by the MRF.

Animals↗

PubMed1990

Vertical and horizontal coding of space in the monkey dorsolateral prefrontal cortex.

Single cell activity in the dorsolateral prefrontal cortex was recorded in a monkey performing a delayed alternation (DA) task in 3 directions, to the left, to the right, and upwards. Among the 127 units studied in all three directions, 18 neurons were spatially selective in one direction (to the left, to the right or upwards), 37 neurons in two directions and 8 neurons in each 3 directions during the performance of the DA task. Of the 9 neurons that were spatially selective upwards, 8 had a specific pattern of activity during the delay period and one during the response period. When several spatial directions are studied in a DA task, as in this work, it becomes evident that the prefrontal cortex contains a large number of spatially selective neurons. The results of this study suggest that there is a spatial memory map in the prefrontal cortex which is needed not only when a DA task is performed to the left and to the right but also in the upward direction.

Animals↗

PubMed1990

Dexamethasone attenuates exercise-induced dental analgesia in man.

The effect of dexamethasone on exercise-induced adrenocorticotropin (ACTH) secretion and dental analgesia was studied in healthy human subjects. Different levels of exercise (100-200 W) were produced by a cycle ergometer. Dental pain thresholds were tested with a constant current stimulator. Dental pain thresholds were elevated with increasing work loads, and the elevation was still significant 30 min after the end of the exercise. Dexamethasone produced a significant reversal of exercise-induced pain threshold elevations concomitantly with the suppression of exercise-induced ACTH release. The results suggest that the corticotropin releasing factor-ACTH axis is involved in the exercise-induced analgesia.

Adrenocorticotropic Hormone↗

PubMed1990

The effect of systemic cocaine on spontaneous and nociceptively evoked activity of neurons in the medial and lateral thalamus.

In rats, analgesic doses of cocaine (25 mg/kg, i.p.) suppressed the responses of 20 of 22 medial and lateral thalamic neurons to reticular formation and somatic noxious stimuli. The responses of 7 of 8 lateral thalamic neurons to innocuous somatic stimuli were unaffected or enhanced. The suppression of thalamic responses to noxious stimuli may be part of the mechanism underlying cocaine analgesia.

Action Potentials↗

PubMed1990

The effect of medetomidine, an alpha 2-adrenoceptor agonist, in various pain tests.

Medetomidine, a new alpha 2-adrenoceptor agonist produced dose-dependent (30-100 micrograms/kg i.p.) analgesia in the formalin test in rats, and this effect was reversed by atipamezole (1 mg/kg), a new alpha 2-adrenoceptor antagonist. However, medetomidine at the dose of 100 micrograms/kg did not influence tail flick latencies or latencies of the biting response to mechanical pinch stimuli. Moreover, medetomidine produced sedation and a decrease in locomotor activity. In comparison, the non-sedative monoaminergic agent, cocaine (25 mg/kg), produced highly significant analgesic effects in the formalin and mechanical pain tests. The cocaine effect in the formalin test was not reversed by atipamezole (1 mg/kg). It is concluded that the analgesic effect of medetomidine in the formalin test is due to supraspinal mechanisms related to sedation and is mediated by alpha 2-adrenoceptors. The alpha 2-adrenoceptors are not involved in cocaine-induced anagesia.

Adrenergic alpha-Agonists↗

PubMed1990

Cocaine: effect on spinal projection neurons in the rat.

In the anesthetized rat, systemic cocaine at an analgesic dose (25 mg/kg, IP) had no general influence on spontaneous activity in nociceptive spinoreticular tract neurons or in rostrally projecting low-threshold mechanoreceptive neurons of the spinal dorsal horn. Peripherally evoked activity was moderately (mean: 30%) reduced in 43% (6/14) of the spinoreticular tract neurons, whereas in 50% of them there was no marked change in evoked activity by cocaine. Evoked activity was slightly reduced in 25% (2/8) of the low-threshold mechanoreceptive neurons and not changed in 75% of them. The suppressive effect of a distant conditioning noxious stimulus on responses to spinoreticular tract neurons was enhanced by cocaine in 3/6 of the spinoreticular tract neurons. Primary afferent terminal excitability of A-fibers was slightly increased following cocaine as indicated by the increased amplitude (mean: 24%) of the antidromically evoked compound action potential recorded from the sural nerve. It is concluded that the previously shown marked enhancement of spontaneous activity in the bulborecticular formation is generated supraspinally. Thus, while cocaine-induced analgesia appears to be due primarily to supraspinal mechanisms, the present results suggest that spinal mechanisms are also involved possibly presynaptically.

Animals↗

PubMed1990

Spatial features of vibrotactile masking effects on airpuff-elicited sensations in the human hand.

It was recently shown that the cutaneous sensitivity to airpuffs is decreased by a low-frequency vibrotactile masker in the hairy skin, and by a low-frequency but especially by a high-frequency masker in the glabrous skin. In the current study, the spatial features of this masking effect were determined in four healthy human subjects, using a reaction time paradigm. The masking effect decreased monotonically with increasing interstimulus distance, and identically in longitudinal and transverse (i.e., lateral) directions in the palm or dorsal surface of the hand. The masking effect was stronger in the glabrous than in the hairy skin, especially in the fingers. In the glabrous skin, the spread of masking effect produced by a high-frequency masker was more extensive than that produced by a low-frequency masker. The mechanical spread of high-frequency vibration was less extensive than that of low-frequency vibration in the skin. In the glabrous skin, a masker applied to the tip of the finger produced a stronger masking effect on sensations in the base of the finger than when the masker was located at the base and the test stimulus was located at the tip. It is concluded that mechanical spread of vibration in the skin is of minor importance in explaining the masking effects. Different peripheral neural mechanisms underlie the airpuff-elicited sensations in the hairy and glabrous skin. The afferent inhibitory mechanisms are stronger for signals coming from the glabrous skin of the fingers than for signals coming from the hairy skin. Furthermore, the peripheral innervation density and size of the cortical representational areas may be of importance in determining the magnitude of the masking effect.

Adult↗

PubMed1989

Effect of chronic sciatic nerve section on saphenous nerve input to midline bulboreticular formation in the rat.

The sciatic nerve was transected unilaterally 7-10 weeks before electrophysiological single unit recordings were made from somatically activated neurons in the midline bulboreticular formation of the rat. Their responses to high-intensity electrical stimulation of the saphenous nerve area were significantly stronger on the lesioned side. In control rats no such side difference was found. The result indicates that sciatic nerve transection unmasks polysynaptic somatic input to the midline bulboreticular formation.

Animals↗

PubMed1989

Effect of subcutaneous formalin treatment on responses to bulboreticular nociceptive neurons in the rat.

The effect of subcutaneous formalin (5%, 0.05 ml) on responses to nociceptive neurons in the medial bulboreticular formation was studied in barbiturate-anesthetized rats. In general, the activity in the studied neurons was not increased following the application of formalin, except for the first few minutes. Concomitantly, no formalin-induced prolonged increase in spontaneous impulse discharge was seen in nociceptive spinal cord neurons with antidromically identified projections to the bulboreticular formation. Also, following formalin application no hypersensitivity was seen in responses of bulboreticular neurons to high-intensity electric stimuli applied to the paw contralateral to the formalin-treated paw. The results suggest that it is not a general property of nociceptive neurons in the medial bulboreticular formation that they are activated in a prolonged fashion by subcutaneous formalin. It is possible that the medial bulboreticular formation is involved in the first rapid phase but not the second prolonged phase of formalin-induced pain.

Action Potentials↗

PubMed1989

Comparison of tactile discrimination ability of visually deprived and normal monkeys.

The tactile discrimination ability of visually deprived and normal monkeys was tested to study whether loss of vision would improve the utilization of the tactual sense. Three normally sighted monkeys and three monkeys that had been deprived of vision during the first year of their life were trained in two tactile discrimination tasks by using a reward system in which the animals received a raisin or half a peanut under a correctly chosen wooden block. Discrimination was based on the gradual roughness or size of various blocks. When the monkeys had learned the tasks to the criterion, discrimination thresholds were determined. All monkeys improved their performance in both tasks with time, but no statistically significant differences between the performance of the two groups of monkeys were obtained. These results suggest that although the representation of the tactual sense in the cortical association areas has been shown to increase as a result of visual deprivation during the early sensitive period of life, increased representation does not improve the tactual discrimination ability of simple tactual stimuli.

Animals↗