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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study compared the efficacy and the adverse effects of controlled-release morphine (CRM) suspension (SAR 213) and CRM tablets (Moscontin) in the treatment of cancer pain. This multicenter, randomized, double-blind, double-dummy, crossover study was carried out on 52 patients. Each patient received both study treatments given at an equivalent dosage of morphine during each of two 7-day periods. The primary outcome variable was the severity of pain assessed three times daily by means of a visual analogue scale. Secondary criteria of efficacy were the severity of pain assessed by verbal rating scale, the need for "rescue" doses of immediate-release morphine, treatment preference, and indices of quality of life (activity, mood, sleep). There were no statistically significant differences in the parameters assessed when comparing the two groups. This study shows that, when prescribed at the same doses, CRM suspension and CRM tablets have similar efficacy and adverse effects, as well as the same duration of action. The results of this first clinical study carried out on CRM suspension are especially relevant for patients with cancer pain who have difficulty swallowing.
J Pain Symptom Manage 1992 Oct
PMID:A comparative study of controlled-release morphine (CRM) suspension and CRM tablets in chronic cancer pain. 148 92

The synthesis and analgesic testing of 3-[4-(1,1-dimethylheptyl)-2-hydroxyphenyl]cyclohexanol (1) are described. Prior (SAR) studies led us to conclude that the pyran ring of 9-nor-9 beta-hydroxyhexahydrocannabinol (HHC) was not necessary for the expression of biological activity in this series of cannabinoids. Analysis of models and the use of molecular mechanics calculations suggested that a simpler compound, such as 1, would possess the biological activity of HHC. Compound 1 was prepared in nine steps from [3-(benzyloxy)phenyl]acetonitrile (2). Biological testing in five models of pain shows that compound 1 and morphine are equally potent as analgesics and demonstrates that the pyran ring of HHC is not necessary for biological activity. Further simplification of 1 was pursued by the synthesis of 4-[4-(1,1-dimethylheptyl)-2-hydroxyphenyl]-2-pentanol (17), but this derivative exhibits significantly reduced analgesic activity.
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PMID:A cannabinoid derived prototypical analgesic. 669 Jun 85

Published experimental data for three thermal/harmful bioelectromagnetic effects (lethality, cataractogenesis, and threshold pain sensation) are examined in an effort to develop a generally consistent empirical expression relating the time of irradiation necessary to induce an effect to the intensity of the radiation. A critical organ is assigned to each effect and the SAR's in these organs are estimated, when necessary, from the incident power density. It is found that all the data can be satisfactorily described by a single power function expression which gives the exposure duration as a function of the SAR in the critical organ and an experiment-specific constant.
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PMID:An empirical time-intensity relationship for thermal bioelectromagnetic effects. 692 91

Between August 1989 and July 1992 a total of 22 patients (64 treatments) with inoperable or recurrent deep seated pelvic tumours were treated with regional hyperthermia and radiotherapy. The 70 Mhz Coaxial TEM applicator with its characteristic open waterbolus was used as heating device. The main objective of this pilot study was to evaluate the feasibility, toxicity and temperature data. The results showed that the major treatment limiting factors were insufficient power and systemic stress. Local pain was observed in only 10% of all treatments. Most of the treatments resulted in elevated systemic temperatures with the overall mean maximum oesophagus temperature reaching 38.9 +/- 0.7 degrees C, however, in only 6% of these treatments this was found to be treatment limiting. From the measured data the following intratumoral temperatures were calculated: T90 = 39.9 +/- 1.0 degrees C; T50 = 40.7 +/- 1.0 degrees C; T10 = 41.4 +/- 1.0 degrees C. In addition, the overall mean average normal tissue temperatures were determined: Trectum = 40.8 +/- 0.7 degrees C; Tvagina = 41.3 +/- 0.9 degrees C; Turethra = 40.8 +/- 0.9 degrees C. The temperatures in normal tissue were frequently higher than in tumour, indicating that a large volume was heated. The open waterbolus allows strong cooling, but the strategy was changed during the study: higher systemic temperatures were allowed to improve the pelvic temperatures. This pilot study proved that the open waterbolus is clinically a success, because it offers patient comfort and SAR-steering by patient repositioning, and that regional hyperthermia with the Coaxial TEM is feasible.
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PMID:Regional hyperthermia of pelvic tumours using the Utrecht 'Coaxial TEM' system: a feasibility study. 779 Jul 33

Selective N-type voltage sensitive calcium channel (VSCC) blockers have shown utility in several models of stroke and pain. We are especially interested in small molecule N-type calcium channel blockers for therapeutic use. Herein, we report a series of N,N-dialkyl-dipeptidylamines with potent functional activity at N-type VSCCs and in vivo efficacy. The synthesis, SAR, and pharmacological evaluation of this series are discussed.
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PMID:N,N-dialkyl-dipeptidylamines as novel N-type calcium channel blockers. 1020 59

Selective N-type voltage sensitive calcium channel (VSCC) blockers have shown efficacy in several animal models of stroke and pain. In the process of searching for small molecule N-type calcium channel blockers, we have identified a series of N-methyl-N-aralkyl-peptidylamines with potent functional activity at N-type VSCCs. The most active compound discovered in this series is PD 173212 (11, IC50 = 36 nM in the IMR-32 assays). SAR and pharmacological evaluation of this series are described.
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PMID:Structure-activity relationship of N-methyl-N-aralkyl-peptidylamines as novel N-type calcium channel blockers. 1046 35

The synthesis and SAR of a novel series of non-nucleoside pyridopyrimidine inhibitors of the enzyme adenosine kinase (AK) are described. It was found that pyridopyrimidines with a broad range of medium and large non-polar substituents at the 5-position potently inhibited AK activity. A narrower range of analogues was capable of potently inhibiting adenosine phosphorylation in intact cells indicating an enhanced ability of these analogues to penetrate cell membranes. Potent AK inhibitors were found to effectively reduce nociception in animal models of thermal hyperalgesia and persistent pain.
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PMID:Structure-activity studies of 5-substituted pyridopyrimidines as adenosine kinase inhibitors. 1114 Jul 40

Local pain is the main factor that limits regional hyperthermia treatment. Using the SAR model of the regional hyperthermia treatment planning system, the capability of absorbing blocks to reduce peripheral hot spots was investigated. The effect of rectangular absorbers of various size and salinity on an elliptical phantom in the Coaxial TEM was evaluated. The computed results were compared with SAR values measured in the phantom. Absorbers of 9 x 9 x 4 cm3 and a salinity of 18 gram l(-1) provide a SAR reduction in the muscle equivalent material, centrally under the absorber of at least 50% at a depth of up to 3 cm. The effect on the central (i.e. tumour) region is less than 20%. Larger absorbers have a more global effect and cause more attenuation in the central region. The attenuating effect depends strongly on the thickness of the fat layer between muscle and absorber. More than 2 cm fat limits the effective use of absorbers. Absorbers can induce a significant increase of SAR in muscle and fat near their edges. This effect also depends on absorber size and salinity and the thickness of the fat layer. The effect of an absorber was also evaluated with a patient anatomy, yielding results in agreement with the phantom experiments.
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PMID:The use of absorbing structures during regional hyperthermia treatment. 1134 29

In hyperthermia treatments performed with a radio-frequency phased array, the main issue to apply the excitation amplitudes and phases of the applicators for which tumour heating is optimal, i.e. the maximal therapeutic gain without unwanted side effects. Due to the complex interaction of the radiated EM-field and the patient's tissues, it is very difficult to find these optimal excitation (amplitude and phase) parameters by intuition. Calculation of the EM-field distribution within the patient can aid in finding the optimal excitation setting. However, this remains a difficult task because of the degrees of freedom available (2n - 1, with n the number of applicators in the array) and because a large temperature elevation may occur at healthy tissue sites resulting in unwanted side effects, e.g. pain or healthy tissue damage. Therefore, determining the excitation amplitudes and phases yielding optimal tumour heating can be done effectively only by application of a computerized optimization procedure. Optimization of the temperature distribution in the patient requires detailed knowledge of the thermal tissue parameters. Techniques for determining these properties are not commonly available and the use of averaged values for parameters like the tissue perfusion is expected to introduce large errors for individual patient treatment planning. As a consequence, the SAR distribution, being proportional to the temperature increase at treatment start, is more often selected for optimization. The 'optimized' excitation amplitudes and phases are found by maximization of a certain SAR ratio. Several propositions for this SAR ratio have been reported in the literature, e.g. the ratio of the SAR at the tumour site and the SAR at sites where unwanted side effects may occur. However, the definition of these ratios does not constrain the SAR value at these tissue locations to a safe value. In this paper, a tool for the optimization of the SAR distribution including the specification of constraints is presented. The tool focuses on the definition of the average SAR as a function of the excitation amplitudes and phases in a volume of arbitrary size (e.g. the tumour volume or the whole patient volume). These functions can be applied in either customized or commercially available optimization routines and they enable the definition of constraints for the average SAR in a certain volume. The described tool is illustrated for a patient case, showing the flexibility and easy application of the tool.
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PMID:A flexible optimization tool for hyperthermia treatments with RF phased array systems. 1192 90

Hodgkinsine, a trimeric pyrrolidinoindoline type alkaloid, present as a major constituent of Psychotria spp. (Rubiaceae), has shown to produce dose-dependent, naloxone reversible, analgesic effect in thermal models of nociception and in the capsaicin-induced pain. SAR studies have been initiated by synthesizing the three diastereomeric dimers (chimonanthines) (11-13) which were evaluated in vitro and in vivo along with the synthetic intermediates. Strong binding affinities for mu opioid receptors were found for (-)- and (+)-chimonanthine monourethanes (9 and 10), whereas (-)-, (+)- and (meso)-chimonanthine (11-13) and hodgkinsine displayed low affinity. In vivo data have shown that only (+)-chimonanthine (12) and calycosidine resemble the analgesic profile found for hodgkinsine.
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PMID:Synthesis and antinociceptive activity of chimonanthines and pyrrolidinoindoline-type alkaloids. 1198 9


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