Pain
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Meta Analysis
Placebo effects on cutaneous pain and itch: a systematic review and meta-analysis of experimental results and methodology.
Placebo effects, positive treatment outcomes that go beyond treatment processes, can alter sensations through learning mechanisms. Understanding how methodological factors contribute to the magnitude of placebo effects will help define the mechanisms by which these effects occur. We conducted a systematic review and meta-analysis of experimental placebo studies in cutaneous pain and itch in healthy samples, focused on how differences in methodology contribute to the resulting placebo effect magnitude. ⋯ Other methodological and demographic factors did not significantly affect placebo magnitudes. Placebo effects on pain and itch reliably occur in experimental settings with varied methods, and conditioning with verbal suggestion produced the strongest effects. Although methods may shape the placebo effect to some extent, these effects appear robust overall, and their underlying learning mechanisms may be harnessed for applications outside the laboratory.
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Central sensitization (CS) is defined as an increased nociceptive responsiveness due to sensitization of neurons in the central nervous system, usually the result of prolonged nociceptive input or a disease state associated with noxious inputs (eg, polyarthritis). The concept of CS has recently been adopted in clinical assessments of chronic pain, but its diagnosis in humans may now include a wide range of hypervigilant responses. The purpose of this review is to ascertain whether self-report questionnaires linked with CS are associated with enhanced nociceptive responses or whether they measure sensitivity in a broader sense (ie, emotional responses). ⋯ The PSQ did, however, correlate strongly with phasic heat and tonic cold pain tests. The studies reviewed did not provide sufficient evidence that self-report measures reflect a canonical understanding of CS. The CSI more closely reflects psychological hypervigilance than increased responsiveness of nociceptive neurons.
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Supplemental Digital Content is Available in the Text.
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Fentanyl exhibits interindividual variability in its dose requirement due to various nongenetic and genetic factors such as single nucleotide polymorphisms (SNPs). This study aims to develop and cross-validate robust predictive models for postoperative fentanyl analgesic requirement and other related outcomes in patients undergoing major breast surgery. Data regarding genotypes of 10 candidate SNPs, cold pain test (CPT) scores, pupillary response to fentanyl (PRF), and other common clinical characteristics were recorded from 257 patients undergoing major breast surgery. ⋯ The variant genotype of CTSG (rs2070697), higher intraoperative fentanyl use, and higher CPT scores were associated with significantly lower TFA. The predictive models for 24-hour postoperative fentanyl requirement, pain scores, and TFA had R-squared values of 0.313 (SVM-Linear), 0.434 (SVM-Linear), and 0.532 (RF), respectively. We have developed and cross-validated predictive models for 24-hour postoperative fentanyl requirement, 24-hour postoperative pain scores, and TFA with satisfactory performance characteristics and incorporated them in a novel web application.
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Physiological or pathology-mediated changes in neuronal activity trigger structural plasticity of the action potential generation site-the axon initial segment (AIS). These changes affect intrinsic neuronal excitability, thus tuning neuronal and overall network output. Using behavioral, immunohistochemical, electrophysiological, and computational approaches, we characterized inflammation-related AIS plasticity in rat's superficial (lamina II) spinal cord dorsal horn (SDH) neurons and established how AIS plasticity regulates the activity of SDH neurons, thus contributing to pain hypersensitivity. ⋯ We show that AIS shift back close to the soma, and SDH inhibitory neurons' excitability increases to baseline levels following recovery from inflammatory hyperalgesia. The computational model of SDH inhibitory neurons predicts that the distal shift of AIS is sufficient to decrease the intrinsic excitability of these neurons. Our results provide evidence of inflammatory pain-mediated AIS plasticity in the central nervous system, which differentially affects the excitability of inhibitory SDH neurons and contributes to inflammatory hyperalgesia.