Search PubMed⌕ Search

Biomedical subjects

W Maixner

Publications and source records attributed to W Maixner.

At least 73 records · Page 4Linked to original sources
PubMed1989

Autonomic and somatosensory interactions: physiological and pathophysiological implications.

Painful or tissue damaging stimuli produce complex sensory, vascular, and neuroendocrine responses. These responses are adaptive in the sense that they provide a warning signal (i.e. pain) and prepare the organism to deal with the threat. Responses to painful stimuli do not occur independently of each other and many of the physiological responses to painful stimuli may act to diminish the perception of pain. Experimental findings are reviewed supporting the hypothesis that vascular responses which stimulate baroreceptor afferents engage central pain inhibitory networks. The importance of cardiovascular and somatosensory interaction as they relate to adaptive and maladaptive conditions will be discussed.

Adaptation, Physiological↗
PubMed1986

Wide-dynamic-range dorsal horn neurons participate in the encoding process by which monkeys perceive the intensity of noxious heat stimuli.

The role of dorsal horn wide-dynamic-range (WDR) and nociceptive-specific (NS) neurons in the encoding of the perceived intensity of noxious stimuli was determined while monkeys detected near-threshold changes in the intensity of noxious heat stimuli. Behavioral detection latencies were a reliable measure of the perceived intensity of these stimuli. There was a significant correlation between behavioral detection latency and neuronal discharge of WDR, but not NS neurons. In addition, WDR neurons exhibited greater activity on correctly detected vs non-detected trials, whereas NS neurons did not. We conclude that WDR neurons are involved in the encoding process by which monkeys perceive the intensity of noxious heat stimuli near detection threshold.

Animals↗
PubMed1986

Dorsal horn opiate administration attenuates the perceived intensity of noxious heat stimulation in behaving monkey.

In monkeys trained to detect and discriminate noxious heat stimuli, morphine microinjected into the medullary dorsal horn attenuated the perceived intensity of noxious heat in a dose- and stimulus-dependent fashion. These data demonstrate a pharmacologically specific effect of opiates on the sensory intensity component of pain at the earliest central relay pathway transmitting noxious information.

Animals↗
PubMed1986

The relationship between cardiovascular and pain regulatory systems.

An increasing amount of anatomical, physiological, and pharmacological evidence suggest that pain inhibitory circuitry is linked with cardiovascular regulatory systems in man and laboratory animals. Induction of hypertension in rats by different methods (mineralocorticoid treatment, stenosis of renal artery, or social deprivation) is associated with reduced responsiveness to noxious thermal stimuli (hot-plate) or to noxious mechanical stimuli (paw pressure). Genetically hypertension-prone rats derived from the SABRA strain and spontaneously hypertensive rats derived from Wistar/Kyoto strain also display a similar hypoalgesia. Acute increases in blood pressure are associated with reduced sensitivity to painful stimuli. Additionally, the interaction between blood pressure and pain perception has also been supported by the demonstration that various experimental interventions that diminish the magnitude of hypertension also attenuate the hypoalgesia. Recent clinical findings are also in agreement with the laboratory animal findings since sensory and pain thresholds have been shown to be significantly higher in unmedicated essential hypertensive subjects compared to normotensive controls. Thus, the human data corroborate animal data and suggest that a relation between blood pressure and pain sensitivity is likely to be a general phenomenon. It is unlikely that damage to peripheral pain fibers caused by a change in blood pressure contributes to the observed hypoalgesia. Naloxone, which has no effect on blood pressure, returns the pain sensitivity to normal levels. Behavioral tests (open field and motor activity cage) of normotensive and of renal and genetically (SBH and SHR) hypertensive rats exclude the possibility of a general motor deficit in hypertensive rats. Endogenous opioid peptides in central and peripheral nervous systems as well as in endocrine organs are implicated, although non-opioid mechanisms are also evident. Activation of baroreceptor afferents by acute or chronic increases in arterial or venous blood pressure may play an important role in the somatosensory responses associated with the increase in blood pressure. Coordinated cardiovascular-pain regulatory responses may be part of an adaptive mechanism that helps the body to face stressful events.

Adaptation, Physiological↗
PubMed1986

The medullary dorsal horn: a target for the expression of opiate effects on the perceived intensity of noxious heat.

We examined the effects of morphine microinjected into the medullary dorsal horn (MDH) on the ability of monkeys to detect temperature increases in the noxious heat range. Behavioral detection latency and the percentage of correct detections were used as measures of the perceived intensity of noxious heat stimuli. Three monkeys were trained to detect a change (T2) of 0.4, 0.6, or 1.0 degrees C from a previous noxious heat level of 46 degrees C (T1). Effects on attentional, motivational, and motoric aspects of the monkeys' behavior were assessed by having them detect innocuous cooling and visual stimuli in tasks of similar difficulty. Morphine (1, 3, and 10 micrograms) microinjected into the MDH produced a dose-dependent and stimulus-intensity-dependent increase in the latency to detection of the T2 stimuli. These effects were opiate receptor-mediated since they were antagonized by systemically administered naloxone (0.5 mg/kg, i.m.) given 40 min after the microinjection of morphine. There were no effects of morphine on the behavioral detection latencies to the innocuous cooling and visual stimuli, indicating that the effects of morphine were modality-specific and independent of changes in motivation, attention, or motoric ability. These data demonstrate a pharmacologically specific effect of opiates on the perceived intensity of noxious heat stimuli at the earliest central relay pathway transmitting noxious information.

Animals↗
PubMed1985

Attentional influences on noxious and innocuous cutaneous heat detection in humans and monkeys.

This study examines whether selective attention can influence sensory-discriminative aspects of nociception in humans and monkeys trained to detect innocuous and noxious thermal stimuli. Human subjects had two contact thermodes positioned bilaterally above the upper lip. Upon trial initiation both thermodes heated to either 39 degrees C, an innocuous warm temperature, or 45 degrees C, a slightly noxious temperature. After 4 to 9 sec, the temperature of one thermode increased an additional step of less than 1 degree C. Subjects released a button when they detected this second temperature increase (T2). Three types of trials were presented in order to assess the effects of spatially selective attention on thermal detection. On 40% of the trials a light correctly signaled the location of the thermode on which T2 would occur. On 10% of trials a light incorrectly signaled the location of T2. No signal was presented on the remaining trials. From the 45 degrees C base line, detection latencies were shortest in the correct signal condition, longest in the incorrect signal condition, and intermediate in the unsignaled condition. The percent of undetected T2s was greatest in the incorrect signal condition and least in the correct signal condition. From the 39 degree C base line, the detection latency in the incorrect signal condition was greater than in the unsignaled condition, but the latter latency was not different from the correct signal latency. In addition, the percent of undetected T2s was the same on all three types of trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Role of the right vagal nerve trunk in antinociception.

Activation of the cardiopulmonary reflex arc by volume expansion results in antinociception of the tail-flick response to radiant heat, and this antinociception can be attenuated by resection of the right vagal nerve trunk. Resection of the right vagal nerve trunk also attenuates foot-shock induced analgesia ( FSIA ), but this vagal influence appears to be qualitatively different from that produced by volume expansion. These findings indicate that pain perception is modulated by cardiovascular input.

Afferent Pathways↗
PubMed1984

Interactions between cardiovascular and pain regulatory systems.

A review of pharmacological, neuroanatomical, electrophysiological, and behavioral data indicates that systems controlling cardiovascular function are closely coupled to systems modulating the perception of pain. This view is directly supported by experiments from our laboratory showing that activation of either the cardiopulmonary baroreceptor reflex arc or the sinoaortic baroreceptor reflex arc induces antinociception. The outcomes of studies using pharmacological treatments, peripheral nerve stimulation, peripheral nerve resection, and CNS lesions are also presented as a preliminary means of characterizing cardiovascular input to pain regulatory systems. The network formed by these systems is proposed to participate in the elaboration of adaptive responses to physical and psychological stressors at various levels of the neuroaxis, and possibly to participate in "diseases of adaptation." In particular, the present analysis suggests that the inhibition of pain brought about by elevations in either arterial or venous blood pressure may provide a form of psychophysiological relief under situations of stress and contribute to the development of essential hypertension in humans.

Afferent Pathways↗
PubMed1984

[D-Ala2]-methionine enkephalinamide reflexively induces antinociception by activating vagal afferents.

Experiment 1 showed that intravenous administration of [D-Ala2]-methionine enkephalinamide resulted in dose-dependent inhibition of the tail-flick reflex, mild hypotension, and bradycardia. The enkephalinamide-induced inhibition of the tail-flick reflex and cardiovascular effects were eliminated in the bilateral cervical vagotomized anesthetized rat preparation, but were unaffected by either a unilateral right vagotomy or bilateral sinoaortic deafferentation in the conscious rat preparation. Experiment 2 demonstrated that the antinociceptive and cardiovascular actions of enkephalinamide were eliminated by pretreatment with intravenous administration of the opioid-receptor antagonist naloxone. These experiments strongly suggest that peripherally circulating enkephalins could reflexively induce analgesia by activating cardiopulmonary receptors whose afferents travel in the vagi.

Afferent Pathways↗
PubMed1984

Effects of naloxone on canine cerebral vascular smooth muscle.

The pharmacological effects of naloxone on cerebral arterial smooth muscle in vitro were examined using canine basilar arterial strips. Naloxone exerted two different effects on canine basilar artery: (1) at a high concentration (3 X 10(-4) M) it produced nonspecific vasodilation, and (2) at lower concentrations (3 X 10(-7), 3 X 10(-6), and 3 X 10(-5) M) it inhibited the vasoconstrictor effects of norepinephrine without altering KCl-, serotonin-, or hemoglobin-induced constriction. Morphine (2 X 10(-5) or 2 X 10(-4) M) did not reverse the specific vasodilating effect of naloxone (3 X 10(-5) M) on norepinephrine-induced constriction. Rather, morphine and naloxone together produced a greater vasodilating effect on norepinephrine-induced constriction than either agent alone. Naloxone (3 X 10(-5) M) failed to alter either phenylephrine-induced constriction or clonidine-induced constriction. The vasodilating effect of naloxone (3 X 10(-5) M) on 10(-3) M norepinephrine-induced constriction was not reduced with 10(-6) M propranolol. These results suggest that the vasodilating effect of naloxone on norepinephrine-induced constriction does not result from an antagonistic action on opiate receptors, direct inhibition of alpha-adrenoreceptors, or direct stimulation of beta-adrenoreceptors in canine cerebral arterial smooth muscle. The vasodilating effect of naloxone on norepinephrine-induced constriction may influence the CBF changes following naloxone administration.

Animals↗
PubMed1983

I. Pharmacological studies with derivatives of 2-aminotetralin, benzhydro[f]quinoline and clonidine suggest a pharmacological identity between peripheral and central alpha-2 adrenoceptors.

A series of hydroxy 2-aminotetralins, benzhydro[f]quinolines and clonidine were used to determine whether a pharmacological similarity could be demonstrated between presynaptic alpha adrenoceptors which modulate autonomic transmission in the guinea pig. Compounds were assayed on isolated field stimulated guinea-pig ilea (GPI) to determine their inhibitory activities on cholinergic transmission. Inhibition of noradrenergic transmission was determined by assaying compounds on isolated field stimulated guinea-pig atria. 2-Aminotetralins, benzhydro[f]quinolines and clonidine impaired cholinergic and noradrenergic transmission by interacting with presynaptic alpha-2 adrenoceptors. A correlation (r = 0.95; P less than .05) was demonstrated between the activity of a compound on the GPI and guinea-pig atria. IC50 values obtained on GPI were correlated with previously reported IC50 values obtained for binding [3H]clonidine sites in homogenates of calf frontal cortex. A significant correlation was demonstrated (r = 0.99; P less than .05). These data suggest that alpha-2 adrenoceptors localized on guinea-pig atria and GPI are pharmacologically similar. In addition, a similar structure activity relationship was demonstrated for presynaptic alpha-2 adrenoceptors on GPI and binding sites labeled by [3H]clonidine in the calf frontal cortex.

Animals↗
PubMed1983

II. Pharmacological studies with derivatives of 2-aminotetralin, benzhydro[f]quinoline, benzhydro[g]quinoline, apomorphine and clonidine suggest a pharmacological dissimilarity between peripheral presynaptic dopamine receptors and alpha-2 adrenoceptors.

This study demonstrates that presynaptic dopamine receptors and alpha-2 adrenoceptors are pharmacologically different. A series of 2-aminotetralins, benzhydro[f]quinolines, benzhydro[g]quinolines, apomorphine and clonidine were studied to determine if they could stimulate presynaptic alpha-2 adrenoceptor and dopamine receptors. Presynaptic dopamine receptor activity was observed in di- and monohydroxy derivatives of 2-aminotetralins, dihydroxy derivatives of benzohydro[f]quinolines and benzohydro[g]quinolines and apomorphine. The greatest presynaptic dopamine receptor activity was observed with agents which maintained the dopamine moiety in the trans coplanar conformation. In contrast to these observations 1) monohydroxy derivatives of 2-aminotetralines were devoid of presynaptic alpha-2 adrenoceptor activity and 2) both cis and trans isomers of dihydroxy derivatives of benzohydro[f]quinolines and benzohydro[g]quinolines exhibited significant presynaptic alpha-2 adrenoceptors activity. These data suggest that presynaptic alpha-2 adrenoceptors and dopamine receptors represent separate functional entities. A discussion on the structure activity relationship associated with presynaptic alpha-2 adrenoceptor and dopamine receptor is provided.

Animals↗
PubMed1982

Factors influencing the altered pain perception in the spontaneously hypertensive rat.

Recent studies have demonstrated a hypoalgesia in hypertensive subjects. This study reports and evaluates factors responsible for the expression of the hypoalgesic behavior demonstrated by genetically hypertensive rats of the Okamoto-Aoki strain (SHR) as compared to normotensive age-matched Wistar-Kyoto rats (WKY). Analgesiometric assays were conducted by the hot plate method. SHR's hypoalgesic behavior was reversed by subcutaneously administered naloxone. The intravenous administration of naloxone did not alter arterial pressure or heart rate in either SHR or WKY. Subcutaneous administration of the peripherally acting ganglionic blocker hexamethonium bromide at a dose which lowered mean arterial blood pressure and thus decreased tonic baroreceptor stimulation, concomitantly reversed the SHR hypoalgesic behavior and induced a hyperalgesia in WKY. Denervation of the sino-aortic baroreceptors failed to alter the hypoalgesic behavior demonstrated by SHR. Denervation of the right vagal nerve trunk with associated cardiopulmonary baroreceptor afferents resulted in a reduction of the SHR hypoalgesic behavior and produced a hyperalgesic behavior in WKY as compared to age-matched sham operated controls over a 4 week period. These data suggest a possible physiological role for vagal afferent systems in the concomitant regulation of resting arterial blood pressure and responsiveness to aversive environmental stimuli. A discussion of the interaction between blood pressure and pain regulatory systems as potential substrates associated with the onset and maintenance of hypertension is provided.

Animals↗
PubMed1982

(+/-)-cis-2-acetoxycyclobutyltrimethylammonium iodide: a semirigid analogue of acetylcholine.

The title compound was prepared to complete a series of small ring (cyclopropane, cyclobutane) cis/trans 1,2-disubstituted semirigid congeners of acetylcholine. A multistep synthetic sequence, beginning with cis-cyclobutane-1,2-dicarboxylic anhydride, permitted unequivocal preparation of the (+/-)-cis target compound 4. The geometry of 4 was confirmed by comparison with an authentic sample of the (+/-)-trans isomer. The cis and trans isomers were equipotent as muscarinic agonists, but they were much weaker than acetyl-beta-methylcholine.

Acetylcholine↗
PubMed1982

Structure-activity relationships of 2-aminotetralins and 2-aminoindanes: inhibitory neuroeffector mechanisms in isolated guinea-pig ilea.

The ability of 2-aminotetralins (2-ATs), 2-aminoindanes (2-AIs), morphine (M) and clonidine (CLON) to alter neuroeffector transmission was studied on field-stimulated (FS) guinea-pig ilea (GPI). The activity of these compounds to inhibit K+, histamine (H), actylcholine (ACh), nicotine (Nic) and serotonin (5-HT) induced contractions was determined using superfused GPI segments. 2-ATs, 2-AIs, M and CLON dose-dependently inhibited contractions produced by low frequency stimulation through alpha-adrenergic, opioid or unknown receptor mediated mechanisms. 2-ATs inhibited ACh, Nic, 5-HT and FS, but not K+- or H-induced contractions. 2-ATs, 2-Ais and M were more potent than hexamethonium in inhibiting Nic-induced contractures. 2-AT and 2-AI-induced inhibition was not antagonized by naloxone or phentolamine. However, the inhibitory effects of 2-ATs. 2-AIs and M on FS-GPI were antagonized by increasing the concentration of Ca2+ ion in the media. These data are consistent with the supposition that 2-ATs, 2-AIs or M alter neuroeffector transmission through competitive changes in Ca2+ disposition in cholinergic neurons of guinea-pig isolated ilea. A discussion relating other biological actions of 2-ATs or 2-AIs (e.g. alpha-adrenergic mediated antinociception) to the observed inhibitory neuroeffector responses is provided.

Acetylcholine↗