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W Maixner

Publications and source records attributed to W Maixner.

At least 19 recordsLinked to original sources
PubMed1992

Delta-opioid-receptor activation by [D-Pen2,D-Pen5]enkephalin and morphine inhibits substance P release from trigeminal nucleus slices.

The release of substance P (SP) from spinal dorsal horn slices is partially inhibited by micromolar concentrations of selective delta-opioid receptor agonists. In the present study, we have examined the effect of nanomolar concentrations of [D-Pen2,D-Pen5]enkephalin (DPDPE, delta-opioid receptor agonist) and low micromolar of concentrations morphine on K(+)-evoked SP release from rat trigeminal nucleus caudalis (TNC) slices. DPDPE and morphine inhibited SP release with an apparent maximal effect at 3 nM and at 3 microM, respectively. DPDPE and morphine produced U-shaped concentration-response curves that were completely autoinhibited at 100 nM DPDPE and 1 microM morphine. The inhibition of SP release produced by 3 nM DPDPE and 3 microM morphine was blocked by the opioid receptor antagonists naloxone (30 nM; non-selective) and ICI 174,864 (0.3 microM; delta-selective) but not by nor-binaltorphimine (3 nM n-BNI; kappa-selective), naloxonazine (1 nM; micro 1-selective) or beta-funaltrexamine (20 nM beta-FNA; mu-selective). These findings indicate that delta-opioid receptor-mediated inhibition of SP release from TNC can be achieved by nanomolar concentrations of selective delta-opioid receptor agonists. Activation of delta-opioid receptors by morphine might be involved in the residual analgesia observed after mu 1-opioid receptor blockade and in the analgesia produced by high doses of morphine.

Analgesics↗
PubMed1992

Relation between systemic hypertension and pain perception.

To test the hypothesis that hypertension diminishes pain perception, a study was made that evaluated the relation between arterial blood pressure and thermal pain perception in human subjects. The average mean arterial pressure in all 20 men studied (10 hypertensive, 10 normotensive) proved to be significantly related to both thermal pain threshold (p = 0.05) and tolerance (p = 0.003). The difference between normotensive and hypertensive groups in baseline and posttest plasma levels of beta endorphin was also significant (p = 0.02) and indicated an interaction between endogenous opioids and blood pressure. Other recent studies of hypertension in relation to hypalgesia were also reviewed. An increased pain threshold was found in hypertensive versus normotensive rats. In cats, electrical stimulation of vagal afferent nerves (cardiopulmonary baroreceptors) suppresses nociceptive responses, and both pharmacologic elevation of blood pressure and vascular volume expansion produce antinociception. Together with preliminary findings in human studies, these results indicate an interaction between pain-controlling and cardiovascular regulatory functions that is probably mediated by the baroreceptor system.

Adult↗
PubMed1992

Multiphasic effect of morphine on the release of substance P from rat trigeminal nucleus slices.

It is generally accepted that morphine acts presynaptically to inhibit substance P (SP) release from afferent terminals in the trigeminal nucleus. Recent studies, however, provide evidence that opioids produce both inhibitory and excitatory effects on SP release which are concentration- and receptor subtype-dependent. In the present study, we have examined a wide range of morphine concentrations on K(+)-evoked SP release from rat trigeminal nucleus caudalis slices. Immunoreactive SP was measured in perfusates. Morphine produced multiphasic effects on K(+)-evoked SP release without affecting basal release. A very low nanomolar concentration (1 nM) suppressed release, higher nanomolar concentrations (100-300 nM) facilitated release, a low micromolar concentration (3 microM) suppressed release, and a higher micromolar concentration (30 microM) facilitated release. These effects were abolished by opioid receptor blockade with naloxone (30 nM). Thus, morphine produces a complex bi-directional modulation of SP release from TNC which is concentration- and possibly receptor subtype-dependent.

Animals↗
PubMed1992

Morphine produces a multiphasic effect on the release of substance P from rat trigeminal nucleus slices by activating different opioid receptor subtypes.

Morphine (MOR) produces a concentration-dependent multiphasic effect (inhibitions and facilitations) on K(+)-evoked substance P (SP) release from rat trigeminal nucleus slices. In this study, we tested the action of selective opioid receptor antagonists on this multiphasic effect of MOR. 1 nM MOR produced an inhibition of K(+)-evoked release of SP that was affected only by the selective mu 1-opioid receptor antagonist naloxonazine (1 nM). MOR at 100 nM elicited an increase in SP release which was abolished selectively by the mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA; 20 nM) and attenuated by the delta-opioid receptor antagonist, ICI 174,864 (0.3 microM). 3 microM MOR produced an inhibition of SP release that was reversed only by ICI 174,864 (0.3 microM). MOR at even higher concentrations (30 microM) produced an enhancement of SP release that was reversed selectively by 3 nM n-binaltorphimine (n-BNI; 3 nM), a kappa-opioid receptor antagonist. In slices pretreated with 20 nM beta-FNA and in the presence of 0.3 microM ICI 174,864 (mu- and delta-opioid receptor blockade), both 100 nM and 3 microM MOR elicited a strong facilitation of K(+)-evoked SP release which was sensitive to 3 nM n-BNI. Thus, the increase in SP release produced by 100 nM may be mediated by the simultaneous stimulation of beta-FNA-sensitive mu- and excitatory delta-opioid receptors whereas the facilitation of SP release induced by 30 microM MOR could be due to the activation of kappa-opioid receptors. 1 nM and 3 microM MOR may inhibit SP release by stimulating naloxonazine-sensitive mu 1- and inhibitory delta-opioid receptors, respectively.

Animals↗
PubMed1992

A parametric analysis of the effects of cardiopulmonary vagal electrostimulation on the digastric reflex in cats.

The thoracic trunk and the cardiac branch of the vagus were stimulated electrically in chloralose-anesthetized cats. The experiments were conducted to determine the parameters of vagal afferent stimulation (VAS) capable of producing an inhibition of the digastric reflex (DGR), to assess the duration of this inhibition, and to test whether endogenous opioids mediate the inhibitory effects. In experiments using intermittent trains of pulses, the effects of pulse number (1, 2, 7 or 35 pulses), frequency (13, 66 or 333 Hz), intensity (0.1, 0.5, 1, 2, 3, 4 or 5 mA), and duration (1 or 3 ms) were evaluated. A 7 pulse train (3 mA) was sufficient to produce maximal inhibition (77 +/- 7%) of the tooth-pulp stimulation-evoked DGR regardless of the pulse duration or frequency. These effects were mediated by vagal afferents since stimulation of the central end produced as much inhibition as stimulation of the intact nerve. VAS also significantly reduced the DGR when elicited by tooth-pulp intensities at 1x -5x threshold. In experiments using 90 s of continuous VAS, 16 combinations of frequency and intensity yielded a threshold intensity for DGR inhibition between 0.1 and 0.5 mA and a threshold frequency at 2 Hz. Maximal DGR inhibition was produced at 5 Hz-0.5 mA by VAS. Reflex inhibition occurred within 10 s and outlasted VAS for longer than 60 s. Opiate-receptor blockade did not alter VAS inhibition of the DGR and, thus, opioids are not likely to mediate VAS-induced digastric inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The relationship between plasma beta-endorphin, opioid receptor activity, and silent myocardial ischemia.

OBJECTIVE: To investigate the role of the opioid system in the pathophysiology of silent ischemia through opiate antagonism with naloxone, and to determine the reproducibility of resting and postexercise beta-endorphin levels in predominantly asymptomatic patients with coronary artery disease. DESIGN: Randomized, double-blind, placebo-controlled crossover trial. SETTING: A University hospital referral center. PATIENTS: Ten patients with prior evidence of silent exercise-induced ischemia were studied. INTERVENTION: An infusion of saline placebo or naloxone at two dose regimens of 0.015 mg/kg or 0.15 mg/kg before supine exercise testing during three separate occasions for each patient. OUTCOME MEASURES: Plasma beta-endorphin was measured at rest, immediately after exercise, and 5 min poststress. Timing and severity of angina and exercise hemodynamics were also determined. RESULTS: Seven of 10 patients reported no angina, whereas the other three experienced angina with placebo and after administration of naloxone at both doses. The severity and duration of angina was consistently noted to decrease in these patients after naloxone administration, especially after low-dose naloxone relative to placebo. There were no apparent correlations between beta-endorphin levels and the characteristics of angina in these three patients, nor between beta-endorphin and hemodynamic responses in all patients in the study. CONCLUSIONS: (a) naloxone failed to precipitate angina in this population of patients with silent ischemia; (b) naloxone appears to exert an analgesic effect at low doses; and (c) a variability of 5 pM at rest and 13 pM after exercise might be expected in predominantly asymptomatic patients due to random variation, which is comparable with results found in normal subjects.

Aged↗
PubMed1992

Controversies in the management of brainstem cavernous angioma: report of two cases.

Two cases of cavernous angioma involving the medulla oblongata are presented. Both cases underwent surgical excision with excellent outcome. The use of surgery via craniectomy is contrasted with stereotactic radiosurgery in light of the known natural history of the lesions. As a result, it is suggested that surgical excision provides immediate protection from the risks of recurrent haemorrhage, establishes a tissue diagnosis, allows complete removal at the primary intervention, avoids complications of radiation-induced damage and is performed more easily in these vascular anomalies due to the presence of a capsule with surrounding gliotic tissue. Additionally, it is implied that the natural history of lesions in this region is still unclear. For these reasons, it is suggested that surgical excision should be the primary therapeutic intervention for cavernous angiomata that involve the brainstem.

Adult↗
PubMed1992

Sinusitis-induced subdural empyema.

Over a 17 year period, 1975-91, 10 children were managed who had sinusitis-induced subdural or extradural empyema. Their ages ranged from 6 to 14 years, with a mean of 11 years. All presented with worsening headaches, fever, vomiting, all had neurological abnormalities, and all had symptoms or signs suggestive of sinusitis. Initial computed tomography gave normal results in five cases and the empyema was diagnosed on the second or third scan. All patients had symptoms for at least one to two weeks before the diagnosis was made. Streptococcus milleri was the organism most frequently implicated. Medical treatment was started in all cases on admission, but all required surgical intervention before resolution.

Adolescent↗
PubMed1991

Evaluation of vagal afferent modulation of the digastric reflex in cats.

In the present study, we have examined the relative ability of cervical, thoracic, cardiac and diaphragmatic vagal stimulation to modulate the digastric reflex produced by tooth-pulp stimulation in anesthetized cats. The right maxillary tooth pulp was stimulated and the digastric reflex was recorded from the right digastric muscle. Cervical vagal stimulation produced a biphasic effect on the digastric reflex. The reflex was facilitated at conditioning test intervals less than 20 ms and inhibited at conditioning test intervals between 100 ms and 500 ms. Cardiac and thoracic vagal stimulation did not significantly facilitate the digastric reflex but inhibited the reflex at conditioning test intervals between 50 ms and 500 ms with maximum inhibition observed at 200 ms. In contrast, diaphragmatic vagal stimulation produced a weaker inhibition of the digastric reflex. The relative ability of different vagal segments to inhibit the digastric reflex was: thoracic = cardiac = cervical greater than diaphragmatic. The inhibitory effects were not related to cardiovascular responses to vagal afferent stimulation. These findings suggest cardiopulmonary vagal afferents represent an important source of vagal afferents which modulate the digastric reflex in the cat.

Animals↗
PubMed1991

The effect of pentobarbital anesthesia on the autonomic nervous system control of heart rate during baroreceptor activation.

This study determined the influence of pentobarbital anesthesia on the autonomic nervous system control of baroreceptor mediated reflex bradycardia in the rat. Reflex bradycardia was elicited by phenylephrine-induced hypertension in conscious and pentobarbital anesthetized (PA) rats before and after sympathetic blockade with the beta-1 receptor antagonist atenolol or parasympathetic blockade with the peripherally acting muscarinic receptor antagonist methyl-atropine. Reflex bradycardia was significantly decreased by pentobarbital anesthesia. Cardiosympathetic blockade produced equivalent relative decreases in baroreflex gain in conscious and PA rats. In contrast, parasympathetic nervous system blockade with methyl-atropine produced relatively less inhibition of baroreflex gain in the PA rat compared with the conscious rat. These results suggest that pentobarbital anesthesia decreases baroreflex gain by inhibiting vagally mediated reflex bradycardia.

Anesthesia, General↗
PubMed1990

Aging and pain perception in ischemic heart disease.

Age is a recognized risk factor for coronary artery disease, but the relationship between age and silent ischemia is not well understood. We analyzed the data from 35 rest/stress radionuclide ventriculography examinations in patients with documented ischemic coronary artery disease who had experienced 1 mm ST segment depression accompanied by angina during exercise testing. An index of ischemic cardiac pain perception (PPI) was calculated by subtracting the time of onset of 1 mm ST segment depression from the time of onset of angina. The mean value of PPI was -97 +/- 311 seconds. PPI was significantly correlated with age (r = 0.37, p = 0.03). This suggests that as age increases, perception of pain during myocardial ischemic episodes becomes muted. This relationship remained significant when we controlled for the presence of medication and severity of disease (change in ejection fraction from rest to peak exercise). These findings suggest that age is an independent risk factor for a decreased perception of ischemic cardiac pain, and thus for silent myocardial ischemia.

Adult↗
PubMed1990

Cardiovascular and sensory responses to forearm ischemia and dynamic hand exercise.

The relationship between cardiovascular responses and pain produced by the submaximal-effort tourniquet procedure was evaluated in healthy humans. Graded increases in ischemic pain were associated with graded elevations in arterial blood pressure, forearm vascular resistance, and venous tone. Many of the vascular responses to muscle ischemia were typical of the cardiovascular components of the defense reaction and correlated with both the sensory and affective aspects of ischemic pain. The cardiovascular responses to arm ischemia were distinguishable from those produced by rhythmic hand exercise used to produce ischemia. Dynamic hand exercise produced a transient increase in arterial blood pressure, heart rate, and measures of hand discomfort. These responses were enhanced when dynamic hand exercise was conducted under ischemic conditions. The tightly coupled and coordinated cardiovascular responses elicited by ischemic pain represent integrated adaptive responses to painful stimulation.

Adult↗
PubMed1989

Responses of monkey medullary dorsal horn neurons during the detection of noxious heat stimuli.

1. We examined the activity of thermally sensitive trigeminothalamic neurons and nonprojection neurons in the medullary dorsal horn (trigeminal nucleus caudalis) in three monkeys performing thermal and visual detection tasks. 2. An examination of neuronal stimulus-response functions, obtained during thermal-detection tasks in which noxious heat stimuli were applied to the face, indicated that wide-dynamic-range neurons (WDR, responsive to innocuous mechanical stimuli with greater responses to noxious mechanical stimuli) could be subclassified based on the slope values of linear regression lines. WDR1 neurons exhibited significantly greater sensitivity to noxious heat stimulation than WDR2 neurons or nociceptive-specific neurons (NS, responsive only to noxious stimuli). 3. In one behavioral task, the monkeys detected 1.0 degrees C increases in noxious heat from preceding noxious heat stimuli ranging from 44 to 48 degrees C. WDR1, WDR2, and NS neurons increased their discharge frequency as a function of the intensity of the first noxious heat temperature (T1) as well as the final temperature (T2). The responses of WDR1 neurons were greater than those produced by WDR2 or NS neurons across all the temperatures examined. The order of stimulus presentation affected the responses of WDR1 neurons to 1.0 degrees C increases in the noxious heat range but not those of WDR2 or NS neurons. 4. In a second behavioral task, the monkeys detected small increases in noxious heat (0.2-0.8 degrees C) from a first temperature of 46 degrees C. Although the responses of all three classes of neurons were monotonically related to stimulus intensity, WDR1 neurons exhibited greater sensitivity to small temperature increases than either WDR2 or NS neurons. 5. Subpopulations of all three classes of neurons exhibited responses that were independent of thermal stimulus parameters or sensory modality and that only occurred during the behavioral task. These task-related responses were time-locked to specific behavioral events associated with trial initiation and trial continuation. 6. These data provide evidence that a subpopulation of WDR neurons is the dorsal horn cell type most sensitive to small increases in noxious heat in the 45-49 degrees C temperature range and provides the most information about stimulus intensity. The findings support the view that nociceptive neurons have the capacity to precisely encode stimulus features in the noxious range and that WDR neurons are likely to participate in the monkeys' ability to perceive the intensity of such stimuli.

Afferent Pathways↗
PubMed1989

The correlation of monkey medullary dorsal horn neuronal activity and the perceived intensity of noxious heat stimuli.

1. We examined the relationship between the activity of medullary dorsal horn nociceptive neurons and the monkeys' ability to detect noxious heat stimuli. In two different detection tasks, the temperature of a contact thermode positioned on the monkey's face increased from 38 degrees C to temperatures between 44 and 48 degrees C (T1). After a variable time period, the thermode temperature increased an additional 0.2-1.5 degrees C (T2), and the monkeys' detection speed from the onset of T2 was determined. We previously have established that detection speed is a measure of the perceived intensity of noxious thermal stimuli. Nociceptive neurons were classified as wide-dynamic-range (WDR, responsive to innocuous mechanical stimuli with greater responses to noxious mechanical stimuli) and nociceptive-specific (NS, responsive only to noxious stimuli). WDR neurons were subclassified as WDR1 and WDR2 based on the higher slope values of the stimulus-response functions of WDR1 neurons. The monkeys were trained to detect small increases in noxious heat, and their detection speeds were correlated with the responses of WDR1, WDR2, and NS neurons. 2. Detection speeds to T2 temperatures of 1.0 degrees C from preceding T1 temperatures of 45 and 46 degrees C were faster during a preceding ascending series of stimuli than during a descending series. Similarly, the peak discharge frequencies of WDR1 neurons in response to the same stimuli were greater during the ascending series of T2 temperatures. In contrast, the responses of WDR2 and NS neurons showed no significant differences during the ascending and descending series of stimuli. 3. Detection speeds following 0.4, 0.6, and 0.8 degrees C T2 stimuli were higher when the preceding T1 temperature was 46 degrees C as compared with detection speeds to the identical stimuli when the preceding T1 temperature was 45 degrees C. WDR1 neurons also exhibited a significant increase in peak discharge frequency to these same T2 stimuli when the preceding T1 temperature was 46 degrees C. In contrast, the neuronal activity of WDR2 and NS neurons did not differ on 45 and 46 degrees C T1 trials. 4. The relationship between detection speed and neuronal peak discharge frequency was examined in response to different pairs of T1 and T2 stimuli when T1 was either 45 or 46 degrees C. There was a significant correlation between detection speed and neuronal discharge for WDR1 and WDR2 neurons. No correlation was observed for NS neurons. 5. The magnitude of neuronal activity on correctly detected and nondetected trials was compared when T1 was 46 degrees C and T2 was 0.2 degree C.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
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↗
PubMed1978

Reactive hyperemia vs treadmill exercise testing in arterial disease.

We compared the ankle pressure response during reactive hyperemia to the response to treadmill exercise in 28 limbs of 14 normal individuals and 26 legs of 15 patients with arterial occlusive disease. The mean percent maximum drop in ankle blood pressure during reactive hyperemia in normal limbs, 17% +/- 11% (+/- 1 SD) was significantly less than that of legs with arterial disease, 54% +/- 15% (P less than .001). Abnormal values were recorded in all but three diseased limbs. There was good correlation between the ankle pressure responses to reactive hyperemia and treadmill exercise (r = 0.71, P less than .001). This study suggests that measurement of ankle pressure during reactive hyperemia may be a useful substitute for treadmill testing to determine the functional capacity of the circulation during stress in patients with arterial occlusive disease. Reactive hyperemia testing requires less time and equipment and may be performed in patients who might be at risk or unable to carry out treadmill exercise.

Adult↗