Pain
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Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) and blocks prostaglandin (PG) biosynthesis associated with inflammatory conditions. In a model of peripherally induced inflammatory pain in rats, celecoxib, given systemically, induced a state of hypoalgesia where the nociceptive threshold was raised above basal values, an effect not observed after treatment with non-selective inhibitors of COX (indomethacin, piroxicam). Here, we have assessed the possibility that these atypical effects of celecoxib could be mediated by action at a site in the CNS. ⋯ Bestatin, an inhibitor of metabolism of endogenous opioid peptides, given i.c.v., potentiated the analgesic effects of a low dose of celecoxib. Taken together, these data indicate that celecoxib could act centrally after systemic administration to produce its characteristic profile of analgesia in this model of peripheral inflammatory pain. Moreover, this atypical analgesia appeared to be mediated by endogenous opioids rather than by inhibition of PG biosynthesis.
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Evidence that patients with chronic pain selectively attend to pain-related stimuli presented in modified Stroop and dot-probe paradigms is mixed. The pain-related stimuli used in these studies have been primarily verbal in nature (i.e., words depicting themes of pain). The purpose of the present study was to determine whether patients with chronic pain, relative to healthy controls, show selective attention for pictures depicting painful faces. ⋯ The results of these analyses revealed that while chronic pain patients with high and low levels of fear both shifted attention away from happy faces, those with low fear shifted attention away from painful faces, whereas those with high fear shifted attention towards painful faces. These results suggest that patients with chronic pain selectively attend to facial expressions of pain and, importantly, that the tendency to shift attention towards such stimuli is positively influenced by high fear of pain/(re)injury. Implications of the findings and future research directions are discussed.
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Repetitive transcranial magnetic stimulation (rTMS) has had partly incongruous effects on cutaneous sensibility, and there are no systematic studies on the effects of rTMS on facial sensory function. We assessed modulation of thermal sensitivity of facial skin in healthy subjects by navigated rTMS (10 Hz), enabling accurate localization of predefined cortical targets: right primary motor cortex (M1) of facial muscles, primary somatosensory cortex (S1) representing the cheek, dorsolateral prefrontal cortex (DLPFC), and secondary somatosensory cortex (S2); the control site was occipital cortex (OCC). Applying signal detection theory, we investigated whether the rTMS-induced changes in heat-pain threshold (HPT) relate to an alteration in the subject's discriminative capacity (sensory factor) or response criterion (non-sensory factor). ⋯ Stimulation of M1 decreased capacity to discriminate painful heat without influencing HPT; there was large interindividual variation in rTMS effects in the M1/S1 areas. Detection threshold for innocuous warming rose similarly after rTMS of M1, S1, DLPFC, S2 and OCC, whereas sensibility to innocuous cooling transiently improved after rTMS of S1. The results indicate that rTMS applied anatomically accurately to S2 may produce analgesia in the face via multiple mechanisms, partly depending on gender, and involving decreased discriminative capacity and increased response criterion.
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Randomized Controlled Trial Controlled Clinical Trial
No evidence for the development of acute tolerance to analgesic, respiratory depressant and sedative opioid effects in humans.
It is widely accepted that chronic opioid therapy is associated with the development of pharmacological tolerance. More controversial is the question as to whether acute opioid administration can result in "acute tolerance." The aim of this double-blind, placebo-controlled study in thirty-six healthy human volunteers was to examine whether a 3-h intravenous infusion delivering two different but clinically relevant doses of the mu-opioid receptor agonist remifentanil would result in tolerance to analgesic, respiratory depressant and/or sedative opioid effects. The blood remifentanil concentration versus opioid effect relationship was determined before and after the 3-h infusion. ⋯ Neither dose of remifentanil produced detectable tolerance to any of the measured opioid effects following a 3-h infusion. The study was adequately powered to detect a decrease in potency of 5-24% for analgesia, 20-48% for respiratory depression, and 32% for sedative effects. These results suggest that short-term administration of clinically useful doses of remifentanil is not associated with the development of significant tolerance to analgesic, respiratory depressant, or sedative opioid effects.
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The objective of our study is to evaluate the detection capacity of Colour Duplex Scanning (CDS) in helping to diagnose Pudendal Neuralgia (PNa) by Pudendal Nerve Entrapment (PNE). This technique is being compared to complete Neurological Criteria (NC) based on Diagnostic Score (DS) and Electroneuromyography (ENMG) and secondly, to the results of surgery. This is a prospective study, on a consecutive series of 96 unselected patients evaluated by both CDS and NC. ⋯ Currently, there is no gold standard that can diagnose PNa by PNE with certainty. CDS is a non-invasive technique, demonstrating high diagnostic value to confirm PNE. In this study, we determined a new objective diagnostic criterion, the Pudendal Artery Ratio (PAR), which is very strong at diagnosing PNE but needs to be validated by further studies.