Pain
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Epibatidine has shown antinociceptive effects in various pain models, being 200-fold more potent than morphine. Previous results from our laboratory demonstrated that HO-1 overexpression has an antinociceptive effect in the formalin test. Furthermore, epibatidine was able to induce haeme oxygenase-1 (HO-1). ⋯ Furthermore, the antinociceptive effect of epibatidine was related to the activation of alpha7 and/or alpha9 nAChRs since methyllycaconitine (MLA) and mecamylamine but not dihydro-beta-erythroidine (DHbetaE) reverted this effect. Finally, we showed by flow cytometry and by immunofluorescence that white blood cells of the animals injected with epibatidine expressed more HO-1 than control animals, and this expression was also reverted by MLA pre-treatment. These findings demonstrate that HO-1 induction by epibatidine has antinociceptive and anti-inflammatory effects by the activation of MLA-sensitive nAChRs.
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Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate that diarrhea-predominant IBS (D-IBS) patients display increased intestinal permeability. We have also found that increased intestinal membrane permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. ⋯ Interestingly, the IBS patients with hypersensitivity and increased intestinal permeability had a higher FBDSI score (100.8 + or - 5.4) than IBS patients with normal membrane permeability and sensitivity (51.6 + or - 12.7) and controls (6.1 + or - 5.6) (p<0.001). A subset of D-IBS patients had increased intestinal membrane permeability that was associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal membrane permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli.
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Placebo has been shown to be a powerful analgesic with corresponding reduction in the activation of the pain matrix in the brain. However it is not clear whether the placebo response is reproducible within individuals and what role personality traits might play in predicting it. We induced placebo analgesia by conditioning subjects to expect pain reduction following a sham-treatment in the guise of a local anaesthetic cream applied to one arm. ⋯ A regression model was used to statistically define a placebo responder in terms of personality scores. High dispositional optimism and low state anxiety were found to be significant predictors of placebo response. We suggest that repeated placebo responders are high in dispositional optimism and having a placebo response in the first session causes a drop in state anxiety at the beginning of the repeat session.
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Experimental determination of pain sensitivity has received increasing attention because of emerging clinical applications (including prediction of postoperative pain and treatment response) and scientific implications (e.g. it has been proposed that above-average pain sensitivity is a risk factor for the development of chronic pain disorders). However, the use of experimental pain sensitivity assessment on a broad scale is hampered by its requirements on time, equipment and human resources and the fact that it is painful for the tested subject. Alternatives to experimental pain testing are currently lacking. ⋯ PSQ scores were significantly correlated to experimental pain intensity ratings (r = 0.56, p < 0.001) but not to pain thresholds (r = 0.03). Prediction of experimental pain intensity ratings by the PSQ was better than by pain-associated psychological factors (pain catastrophizing, depression, anxiety). This shows that the PSQ may be a simple alternative to experimental pain intensity rating procedures in healthy subjects and makes the PSQ a highly promising tool for clinical and experimental pain research.