Pain
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The aims of this study were to examine the effect of old age on the pharmacokinetics of morphine and morphine-6 beta-glucuronide (M6G) and their relationships to antinociceptive activity. Morphine (21.0 mumol/kg) or M6G (21.7 mumol/kg) were administered s.c. to young adult and aged male Hooded-Wistar rats. Antinociceptive effect was measured by the tail-flick method at various times up to 2.5 h or 6.5 h after morphine or M6G administration, respectively, and concentrations of morphine, morphine-3 beta-glucuronide (M3G) and M6G in plasma and brain were determined by HPLC. ⋯ The results demonstrate no change in morphine antinociception and pharmacokinetics with age, and suggest that blood-brain barrier permeability and reception sensitivity to morphine are not altered in aged rats. Accumulation of M3G in plasma of aged rats is probably due to diminished renal clearance of M3G in addition to a reduction in the biliary excretion of M3G. The heightened sensitivity of the aged rats to M6G is probably due to the observed altered kinetics of M6G rather than a pharmacodynamic change.
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To describe the hospital symptom experience of seriously ill patients with common illnesses. To assess the independent association of nausea and dyspnea to level of pain. ⋯ Seriously ill patients have a high symptom burden. Patients who have nausea and dyspnea experience more pain than patients without these symptoms, even after adjustment for depression, anxiety, disease type, disease severity and demographic and psychological measures. The causal association between these symptoms and pain remains to be determined. Though pain may cause dyspnea and nausea, the intriguing possibility remains that, in addition to relieving suffering, treating dyspnea and nausea may relieve pain.
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Intradermal capsaicin injection in humans results in primary hyperalgesia to heat and mechanical stimuli applied near the injection site, as well as secondary mechanical hyperalgesia (increased pain from noxious stimuli) and mechanical allodynia (pain from innocuous stimuli) in an area surrounding the site of primary hyperalgesia. This study in rats tested the hypothesis that the secondary hyperalgesia and allodynia observed following intradermal injection of capsaicin was dependent upon activation of voltage sensitive calcium channels in the spinal cord. Responses to application of von Frey filaments of 10 mN and 90 mN bending forces were tested in all rats before and after injection of capsaicin into the plantar surface of a hindpaw. ⋯ However, all three blockers dose dependently prevented the development of secondary mechanical hyperalgesia and allodynia. The threshold to mechanical stimulation with von Frey filaments was also increased significantly in animals treated with these calcium channel blockers when compared to articial cerebrospinal fluid control animals. These data suggest that calcium channels are important for the development of mechanical hyperalgesia and allodynia that occurs following capsaicin injection.
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Randomized Controlled Trial Clinical Trial
The Chronic Pain Grade questionnaire: validation and reliability in postal research.
The Chronic Pain Grade questionnaire has been proposed as an interview-administered, multi-dimensional measure of chronic pain severity in selected populations with chronic pain in the United States of America. It has not previously been tested in the United Kingdom, in self-completion form or in an unselected general population. We undertook a postal survey to assess its reliability, validity and acceptability in these circumstances, using a general practice population in Scotland, with a practice population of 11202 patients. ⋯ Construct validity was confirmed by testing scores against duration of pain and treatment sought for pain. We concluded that the Chronic Pain Grade questionnaire is a useful, reliable and valid measure of severity of chronic pain. It translates well into UK English and is acceptable in general population postal research.
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Randomized Controlled Trial Clinical Trial
Blockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumide.
In patients who reported mild postoperative pain, we evoked a nocebo response, a phenomenon equal but opposite to placebo. Patients who gave informed consent to increase their pain for 30 min received a substance known to be non-hyperalgesic (saline solution) and were told that it produced a pain increase. A nocebo effect was observed when saline was administered. ⋯ The blockade of the nocebo hyperalgesic response was not reversed by 10 mg of naloxone. These results suggest that cholecystokinin mediates pain increase in the nocebo response and that proglumide blocks nocebo through mechanisms not involving opioids. Since the nocebo procedure represents an anxiogenic stimulus and previous studies showed a role for cholecystokinin in anxiety, we suggest that nocebo hyperalgesia may be due to a cholecystokinin-dependent increase of anxiety.