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
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.
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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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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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Primary C-fiber afferents can induce a state of increased excitability in spinal cord neurons amplifying their responsiveness to noxious and innocuous stimuli--the phenomenon of central sensitization. We have examined whether the hypersensitivity to low-intensity stimuli (mechanical allodynia) evoked by C-afferent conditioning inputs is NMDA receptor dependent. The enhancement by C-afferent conditioning stimuli of the normally low or absent cutaneous touch-evoked responses of posterior biceps femoris/semitendinosus flexor motoneurons in the decerebrate-spinal rat has been used as a model of touch-evoked allodynia. ⋯ Treatment with MK 801 some time after the conditioning input when the mechanical hypersensitivity is fully established, also reduced the increased touch-evoked responses. The reduction in threshold and the increase in touch responsiveness induced by cutaneous and muscle noxious C-fiber conditioning stimuli in the rat spinal cord are, therefore, both prevented and reversed by NMDA receptor antagonism. NMDA antagonists may be potentially useful, therefore, in treating postinjury pain hypersensitivity.