Pain
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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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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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Comparative Study
Gender differences in pain ratings and pupil reactions to painful pressure stimuli.
In order to investigate gender differences in pain perception, the present study employed both a psychophysical and a psychophysiological measure. In experiment 1, 20 subjects rated the painfulness of 4 different levels of tonic pressure applied to their fingers using a verbally anchored categorization procedure. In general agreement with studies of pain threshold and tolerance, female subjects reported greater pain at high levels of stimulation, with no gender difference being evident at low pressure levels. ⋯ The pupil dilations seen during the last 10 sec of the 20-sec pressure application turned out to be a highly significant indicator of pain intensity. When female and male subjects were compared on this measure, a similar divergent pattern as in the psychophysical data emerged, with female subjects showing greater pupil dilations at high pressure levels only. The fact that gender differences in pain perception can be demonstrated using an autonomic indicator of pain that is beyond voluntary control suggests that these differences reflect low-level sensory and/or affective components of pain rather than attitudinal or response-bias factors.
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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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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.