Pain
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In a rat model of artificial ureteral calculosis, the aim of the study was to characterize the behavioural manifestations of direct visceral pain and to evaluate the relationship between number, duration and complexity of the visceral episodes and the extent of referred lumbar muscular hyperalgesia. As evidenced by non-stop video-tape recordings over 4-14 days, almost 98% of stone-implanted rats showed episodes similar to the writhing behaviour characteristic of noxious visceral stimulation in animals. From one rat to another, these episodes varied from very few (1-3) to a very high number (+/- 60), lasted a few minutes to over 45 min and were of variable complexity, as evaluated via an arbitrary scale on the basis of the combination of movements. ⋯ Stone-implanted rats displaying visceral episodes also showed hyperalgesia of the ipsilateral oblique musculature, as evidenced by a decrease in the vocalization threshold to electrical muscle stimulation, which was maximum on the first 3-4 days after implantation but lasted up to 10 days. The visceral episodes and the muscle hyperalgesia showed a strict relationship of interdependence: a significant, direct linear correlation was found between number and duration of episodes and tendency to also develop a contralateral muscle hyperalgesia. By applying the results of the study to the interpretation of human pathology, referred lumbar muscle hyperalgesia from ureteral calculosis would appear to be a strict function of the colic pain experienced.
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Clinical Trial Controlled Clinical Trial
Modulation of pressure pain thresholds during and following isometric contraction.
This study aimed at evaluating the influence of submaximal isometric contraction on pressure pain thresholds (PPTs) in 14 healthy volunteers before and after skin hypoesthesia. PPTs were determined with pressure algometry over m. quadriceps femoris before, during, and following an isometric contraction. Maximum voluntary contraction (MVC) was assessed using a computerized dynamometer. ⋯ Isometric contraction of m. quadriceps femoris increase PPTs during and following contraction. The results suggest that input from cutaneous and deeper tissues interacts with nociceptive activity set up by the pressure stimulus. Determining the degree of sensory modulation in muscle and skin in different chronic pain syndromes could become a functional method of patient assessment important for differential diagnosis, treatment evaluation, and follow-up.
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Recent evidence suggests that hyperalgesia and morphine tolerance, two seemingly unrelated phenomena, have in common certain neural substrates such as activation of the N-methyl-D-aspartate (NMDA) receptor and the subsequent intracellular activation of protein kinase C and nitric oxide. Should common cellular elements be involved in hyperalgesia and morphine tolerance, these cellular and intracellular commonalities might be expected to result in interactions between these two phenomena. Indeed, our previous studies have shown that thermal hyperalgesia develops when animals are made tolerant to the antinociceptive effects of morphine. ⋯ In addition, once daily treatment with 10 nmol MK-801 from D2 to D7 after nerve ligation prevented both the development of thermal hyperalgesia and the rightward shift of the morphine antinociceptive dose-response curve on D8. The results indicate that the antinociceptive effects of morphine are reduced in nerve-injured rats in the absence of daily exposure to morphine and that the NMDA receptor activation may have a critical role in mechanisms of this phenomenon. These data provide further evidence indicating that interactions do occur between neural mechanisms underlying thermal hyperalgesia and morphine tolerance.
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Randomized Controlled Trial Clinical Trial
Epidural clonidine analgesia for intractable cancer pain. The Epidural Clonidine Study Group.
Although the vast majority of patients with cancer pain receive effective analgesia from standard therapy, a few patients, particularly those with neuropathic pain, continue to experience severe pain despite large doses of systemic or intraspinal opioids. Animal studies suggest intraspinal alpha 2-adrenergic agonists may be effective in such cases. Eighty-five patients with severe cancer pain despite large doses of opioids or with therapy-limiting side effects from opioids were randomized to receive, in a double-blind manner, 30 micrograms/h epidural clonidine or placebo for 14 days, together with rescue epidural morphine. ⋯ Clonidine, but not placebo, decreased blood pressure and heart rate. Hypotension was considered a serious complication in 2 patients receiving clonidine and in 1 patient receiving placebo. This study confirms the findings from previous animal studies which showed the effective, potent analgesic properties of intraspinal alpha 2-adrenergic agonists and suggests that epidural clonidine may provide effective relief for intractable cancer pain, particular of the neuropathic type.
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Clinical Trial Controlled Clinical Trial
Differential response to pain by very premature neonates.
The ability of very low birth weight (VLBW) premature infants to respond differentially to real versus a sham heelstick conditions was examined in this crossover study. Using a multidimensional assessment of responses of premature infants (n = 48) between 26 and 31 weeks gestational age (GA) at the time of the study, it was found that they respond differentially to real versus sham heelstick both behaviourally and physiologically. The multivariate effect of condition (real/sham) was significant with maximum heart rate and upper facial action (lower facial action was not scored) contributing significantly to the main effect. ⋯ The variability outcome measures of heart rate standard deviation and range of transfontanelle intracranial pressure contributed significantly to the main effect of GA, but not to the effect of condition. Young VLBW premature infants are capable of a multidimensional differential response to pain. GA is an important factor to consider when assessing pain in premature infants.