Pain
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Repeated exposure to pain can result in sensitization of the central nervous system, enhancing subsequent pain and potentially leading to chronicity. The ability to reverse this sensitization in a top-down manner would be of tremendous clinical benefit, but the degree that this can be accomplished volitionally remains unknown. Here we investigated whether a brief (~5 min) cognitive-behavioural intervention could modify pain perception and reduce central sensitization (as reflected by secondary hyperalgesia). ⋯ Furthermore, secondary hyperalgesia was significantly reduced in the regulate group compared with the control group. Reduction in secondary hyperalgesia was associated with reduced pain catastrophizing, suggesting that changes in central sensitization are related to changes in pain-related cognitions. Thus, we demonstrate that central sensitization can be modified volitionally by altering pain-related thoughts.
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The investigation of nocebo effects is evolving, and a few literature reviews have emerged, although so far without quantifying such effects. This meta-analysis investigated nocebo effects in pain. We searched the databases PubMed, EMBASE, Scopus, and the Cochrane Controlled Trial Register with the term "nocebo." Only studies that investigated nocebo effects as the effects that followed the administration of an inert treatment along with verbal suggestions of symptom worsening and that included a no-treatment control condition were eligible. ⋯ In studies in which nocebo effects were induced by a combination of verbal suggestions and conditioning, the effect size was larger (lowest g=0.76 [0.39-1.14] and highest g=1.17 [0.52-1.81]) than in studies in which nocebo effects were induced by verbal suggestions alone (lowest g=0.64 [-0.25 to 1.53] and highest g=0.87 [0.40-1.34]). These findings are similar to those in the placebo literature. As the magnitude of the nocebo effect is variable and sometimes large, this meta-analysis demonstrates the importance of minimizing nocebo effects in clinical practice.
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Although classical trigeminal neuralgia (CTN) is frequently caused by neurovascular contact (NVC) at the trigeminal root entry zone (REZ), both anatomical and MRI studies have shown that NVC of the trigeminal nerve frequently occurs in individuals without CTN. To assess the accuracy of MRI in distinguishing symptomatic from asymptomatic trigeminal NVC, we submitted to high-definition MRI the series of CTN patients referred to our outpatient service between June 2011 and January 2013 (n=24), and a similar number of age-matched healthy controls. Two neuroradiologists, blinded to the clinical data, evaluated whether the trigeminal nerve displayed NVC in the REZ or non-REZ, whether it was dislocated by the vessel or displayed atrophy at the contact site, and whether the offending vessel was an artery or a vein. ⋯ When REZ contact and nerve atrophy coexisted, both specificity and positive predictive value rose to 100%. Meta-analysis showed that REZ NVC was detected in 76% of symptomatic and 17% of asymptomatic nerves (P<.0001), whereas anatomical changes were detected in 52% of symptomatic and 9% of asymptomatic nerves (P<.0001). In conclusion, trigeminal REZ NVC, as detected by MRI, is highly likely to be symptomatic when it is associated with anatomical nerve changes.
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The degree of variability in the patient baseline 7-day diary of pain ratings has been hypothesized to have a potential effect on the assay sensitivity of randomized clinical trials of pain therapies. To address this issue, we obtained clinical trial data from the Food and Drug Administration (FDA) through the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership, and harmonized patient level data from 12 clinical trials (4 gabapentin and 8 pregabalin) in postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Models were developed using exploratory logistic regression to examine the interaction between available baseline factors and treatment (placebo vs active medication) in predicting patient response to therapy (ie, >30% improvement). ⋯ In addition, there was a small but significant age-by-treatment interaction in the PHN model, and small weight-by-treatment interaction in the DPN model. The patient's sex, baseline pain level, and the study protocol had an effect only on the likelihood of response overall. Our results suggest the possibility that, at least in some disease processes, excluding patients with a highly variable baseline 7-day diary has the potential to improve the assay sensitivity of these analgesic clinical trials, although reductions of external validity must be considered when increasing the homogeneity of the investigated sample.
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Randomized Controlled Trial
The association of acetazolamide infusion with headache and cranial artery dilation in healthy volunteers.
The carbonic anhydrase inhibitor acetazolamide causes extracellular acidosis and dilatation of cerebral arterioles. In this study, we tested the hypothesis that acetazolamide also may induce headache and dilatation of cranial arteries. In a randomized double-blind crossover study design, 12 young healthy women were allocated to injection of 1 g acetazolamide or placebo on 2 separate days. ⋯ Compared to placebo, arterial circumference increased after acetazolamide in the basilar artery (P=.002) as well as the cerebral (P=.003), cavernous (P=.002), and cervical (P=.005) parts of the internal carotid artery, but no other extracranial arteries changed after acetazolamide. In conclusion, acetazolamide caused immediate and delayed headache as well as dilatation of intracranial arteries in healthy volunteers. It is possible that extracellular acidosis induced by acetazolamide causes sensitization of cephalic perivascular nociceptors, which, in combination with vasodilatation, leads to delayed headache.