Pain
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A systematic literature review was undertaken to determine if conditioned pain modulation (CPM) is reliable. Longitudinal, English language observational studies of the repeatability of a CPM test paradigm in adult humans were included. Two independent reviewers assessed the risk of bias in 6 domains; study participation; study attrition; prognostic factor measurement; outcome measurement; confounding and analysis using the Quality in Prognosis Studies (QUIPS) critical assessment tool. ⋯ The absence of blinding, a lack of control for confounding factors, and lack of standardisation in statistical analysis are common. Conditioned pain modulation is a reliable measure; however, the degree of reliability is heavily dependent on stimulation parameters and study methodology and this warrants consideration for investigators. The validation of CPM as a robust prognostic factor in experimental and clinical pain studies may be facilitated by improvements in the reporting of CPM reliability studies.
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Variability in blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals reflects the moment-by-moment fluctuations in resting-state fMRI (rs-fMRI) activity within specific areas of the brain. Regional BOLD signal variability was recently proposed to serve an important functional role in the efficacy of neural systems because of its relationship to behavioural performance in aging and cognition studies. We previously showed that individuals who better cope with pain have greater fluctuations in interregional functional connectivity, but it is not known whether regional brain signal variability is a mechanism underlying pain coping. ⋯ We acquired resting-state fMRI and assessed pain threshold, suprathreshold temporal summation of pain, and the impact of pain on cognition in 80 healthy right-handed individuals. We found that regional BOLD signal variability: (1) inversely correlated with an individual's temporal summation of pain within the ascending nociceptive pathway (primary and secondary somatosensory cortex), default mode network, and salience network; (2) was correlated with an individual's ability to cope with pain during a cognitive interference task within the periaqueductal gray, a key opiate-rich brainstem structure for descending pain modulation; and (3) provided information not captured from interregional functional connectivity. Therefore, regional BOLD variability represents a pain metric with potential implications for prediction of chronic pain resilience vs vulnerability.
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Pain sensitivity is an inherited factor that varies strongly between individuals. We investigated whether genetic polymorphisms in the candidate genes COMT, OPRM1, OPRD1, TAOK3, TRPA1, TRPV1, and SCN9A are contributing to experimental pain variability between children. Our study included 136 children and adolescents (8-18 years). ⋯ The combined genotype, based on expected pain sensitivity, OPRM1 118AA/COMT 472 GA or AA genotyped children, was associated with lower pain thresholds (ie, higher pain sensitivity) than were the OPRM1 118GA or GG/COMT 472GG genotyped children. This is the first study reporting on genetic variants and experimental thermal pain in children and adolescents. OPRM1 rs1799971 and the combined OPRM1/COMT genotype could serve as biomarkers for pain sensitivity.
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Studies have suggested that alcohol consumption is strongly related to reduced reporting of chronic widespread pain (CWP) and level of disability in people with CWP or fibromyalgia. Direction of causality has not been established, that is whether the association is due to people's health influencing their alcohol consumption or vice versa. UK Biobank recruited over 500,000 people aged 40 to 69 years, registered at medical practices nationwide. ⋯ In males who reported drinking the same as 10 years previously, there was a U-shaped relationship between amount drunk and odds of reporting CWP (nondrinkers CWP prevalence 2.4%, 19.1-32.1 units/wk 0.4%, >53.6 units/wk 1.0%; adjORs 2.53 95% confidence intervals [1.78-3.60] vs 1 vs 1.52 [1.05-2.20]). In females, there was a decrease in the proportion reporting CWP up to the modal category of alcohol consumption with no further change in those drinking more (nondrinkers CWP prevalence 3.4%, 6.4-11.2 units/wk 0.7%, >32.1 units/wk 0.7%; adjORs 2.11 [1.67-2.66] vs 1 vs 0.86 [0.54-1.39]). This large study has shown a clear relationship between alcohol consumption and reporting of pain even in people who had not reported changing consumption because of health concerns, after adjustment for potential confounding factors.
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The organic cation transporter OCT1 (SLC22A1) mediates uptake and metabolism of the active tramadol metabolite (+)O-desmethyltramadol in the liver. In this study, the influence of OCT1 genetic polymorphisms on pharmacokinetics and analgesic efficacy of tramadol in patients recovering from surgery was analyzed in addition to the CYP2D6 genotype. Postoperative patients who received tramadol through patient-controlled analgesia were enrolled. ⋯ Plasma areas under the concentration-time curves of (+)O-desmethyltramadol were 111.8 (95% confidence interval: 63.4-160.1), 80.2 (65.1-95.3), and 64.5 (51.9-77.2) h·ng·mL in carriers of 0, 1, or 2 active OCT1 alleles (P = 0.03). Loss of OCT1 function resulted in reduced tramadol consumption and increased plasma concentrations of (+)O-desmethyltramadol in patients recovering from surgery. Therefore, analyzing OCT1 next to CYP2D6 genotype might further improve future genotype-dependent dose recommendations for tramadol.