Pain
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Comparative Study
Synergistic interactions between two alpha(2)-adrenoceptor agonists, dexmedetomidine and ST-91, in two substrains of Sprague-Dawley rats.
Several lines of evidence indicate that the antinociception produced by intrathecal administration of the alpha(2)-adrenoceptor agonists dexmedetomidine or ST-91 is mediated by different subtypes of the alpha(2)-adrenoceptor. We recently provided additional pharmacologic evidence for this idea, as well as for differences in the function of these receptors between Harlan and Sasco rats, two widely-used outbred substrains of Sprague-Dawley rat. The present study used isobolographic analysis to further characterize the receptors at which intrathecally administered ST-91 and dexmedetomidine act in these two substrains. ⋯ This conclusion is consistent with the earlier proposal that dexmedetomidine acts predominantly at alpha(2A)-adrenoceptors whereas ST-91 acts predominantly at non-alpha(2A)-adrenoceptors. Recent anatomical evidence indicates that these non-alpha(2A) adrenoceptors may be of the alpha(2C) type. The synergistic combination of an alpha(2A)- and an alpha(2C)-adrenoceptor agonist may provide a unique and highly effective drug combination for the treatment of pain without the sedation produced by an equianalgesic dose of a single alpha(2)-adrenoceptor agonist.
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Intensity dependence of auditory evoked cortical potentials is abnormal in migraine. This study investigated intensity dependence in migraine and healthy families using group comparisons and analysis of individual differences. Migraineurs were characterized by a steeper amplitude/stimulus function slope and more pronounced difference between the amplitudes of N1-P2 on the more and the less intensive tones than healthy age matched subjects. ⋯ Familial prevalence of intensity dependence among first-degree relatives in migraine families was equal to that in healthy families. These findings support the assumption that high-intensity dependence reflects a functional CNS trait which is more pronounced and prevalent in migraine, but may also be found in healthy individuals and in other neuropsychiatric disorders. Increased intensity dependence is only one of several factors contributing to the risk for this form of headache.
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This study outlines the design and validation of a new self-administered instrument for assessing foot pain and disability. The 19-item questionnaire was tested on 45 rheumatology patients, 33 patients who had attended their general practitioner with a foot-related problem and 1000 responders to a population survey of foot disorders. Levels of reported disability were found to be greatest for rheumatology patients and least for community subjects. ⋯ A Cronbach's alpha value of 0.99 and item-total correlation values between 0.25 and 0.62 confirmed the internal consistency of the instrument. Finally the results of a principal components analysis identified three constructs that reflected disabilities that are associated with foot pain: functional limitation, pain intensity and personal appearance. The design of the foot disability questionnaire makes it a suitable instrument for assessing the impact of painful foot conditions in both community and clinical populations.
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Clinical Trial
Do beliefs, coping, and catastrophizing independently predict functioning in patients with chronic pain?
Physical and psychosocial disability in patients with chronic pain have been shown to be associated with patients' pain-related beliefs, tendency to catastrophize, and pain coping strategy use. However, little is known about whether beliefs, catastrophizing, and coping strategies are independently associated with patient adjustment. Identification of specific beliefs, cognitive responses, and coping strategies strongly and independently associated with physical and psychosocial functioning would suggest the importance of targeting those variables for modification in treatment. ⋯ Belief scores significantly and independently predicted both physical disability and depression, after controlling for age, sex, pain intensity, catastrophizing, and coping. Coping scores significantly and independently predicted physical disability, but not depression, whereas catastrophizing independently predicted depression, but not physical disability. These findings suggest the importance of targeting specific pain-related beliefs and coping strategies, as well as catastrophizing, for modification in the treatment of patients with chronic pain.
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Randomised controlled trials (RCTs) alone are unlikely to provide reliable estimates of the incidence of rare events because of their limited size. Cohort, case control, and other observational studies have large numbers but are vulnerable to various kinds of bias. Wanting to estimate the risk of death from bleeding or perforated gastroduodenal ulcers with chronic usage of non-steroidal anti-inflammatory drugs (NSAIDs) with greater precision, we developed a model to quantify the frequency of rare adverse events which follow a biological progression. ⋯ From these numbers we calculated the number-needed-to-treat for one patient to die due to gastroduodenal complications with chronic (>/=2 months) NSAIDs as 1/((0.69x¿6-16%, average 12%¿)-0.002%))=909-2500 (average 1220). On average 1 in 1200 patients taking NSAIDs for at least 2 months will die from gastroduodenal complications who would not have died had they not taken NSAIDs. This extrapolates to about 2000 deaths each year in the UK.