The journal of pain : official journal of the American Pain Society
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High interindividual variability in postoperative opioid consumption is related to genetic and environmental factors. We tested the association between morphine consumption, postoperative pain, and single nucleotide polymorphisms (SNPs) within opioid receptor μ 1 (OPRM1), catechol-O-methyltransferase (COMT), uridine diphosphate glucose-glucuronosyltransferase-2B7, and estrogen receptor (ESR1) gene loci to elucidate genetic prediction of opioid consumption. We analyzed 20 SNPs in 201 unrelated Caucasian patients who underwent abdominal surgery and who were receiving postoperative patient-controlled analgesia-administered morphine. Morphine consumption and pain intensity were dependent variables; age and sex were covariates. A haplotype of 7 SNPs in OPRM1 showed significant additive effects on opioid consumption (P = .007); a linear regression model including age and 9 SNPs in ESR1, OPRM1, and COMT explained the highest proportion of variance of morphine consumption (10.7%; P = .001). The minimal model including 3 SNPs in ESR1, OPRM1, and COMT explained 5% of variance (P = .007). We found a significant interaction between rs4680 in COMT and rs4986936 in ESR1 (P = .007) on opioid consumption. SNPs rs677830 and rs540825 of OPRM1 and rs9340799 of ESR1 were nominally associated with pain Numeric Rating Scale scores. Combinations of genetic variants within OPRM1, COMT, and ESR1 better explain variability in morphine consumption than single genetic variants. Our results contribute to the development of genetic markers and statistical models for future diagnostic tools for opioid consumption/efficacy. ⋯ This article presents the efforts dedicated to detect correlations between the genetic polymorphisms and the clinical morphine effect self-administered by patients using a patient-controlled analgesia pump after major surgery. The clinical effect is expressed in terms of morphine consumption and pain scores. REGISTERED ON CLINICALTRIALS.GOV: NCT01233752.
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Physical exercise can attenuate neuropathic pain (NPP), but the exact mechanism underlying exercise-induced hypoalgesia (EIH) remains unclear. Recent studies have shown that histone hyperacetylation via pharmacological inhibition of histone deacetylases in the spinal cord attenuates NPP, and that histone acetylation may lead to the production of analgesic factors including interleukin 10. We intended to clarify whether histone acetylation in microglia in the spinal dorsal horn contributes to EIH in NPP model mice. C57BL/6J mice underwent partial sciatic nerve ligation (PSL) and PSL- and sham-runner mice ran on a treadmill at a speed of 7 m/min for 60 min/d, 5 days per week, from 2 days after the surgery. PSL-sedentary mice developed mechanical allodynia and heat hyperalgesia, but such behaviors were significantly attenuated in PSL-runner mice. In immunofluorescence analysis, PSL surgery markedly increased the number of histone deacetylase 1-positive/CD11b-positive microglia in the ipsilateral superficial dorsal horn, and they were significantly decreased by treadmill-running. Moreover, the number of microglia with nuclear expression of acetylated H3K9 in the ipsilateral superficial dorsal horn was maintained at low levels in PSL-sedentary mice, but running exercise significantly increased them. Therefore, we conclude that the epigenetic modification that causes hyperacetylation of H3K9 in activated microglia may play a role in producing EIH. ⋯ This article presents the importance of epigenetic modification in microglia in producing EIH. The current research is not only helpful for developing novel nonpharmacological therapy for NPP, but will also enhance our understanding of the mechanisms and availability of exercise in our daily life.
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By 2007, opioid-related mortality in Washington state (WA) was 50% higher than the national average, with Medicaid patients showing nearly 6 times the mortality of commercially-insured patients. In 2007, the WA Interagency Guideline on Opioid Dosing for Chronic Non-cancer Pain was released, which recommended caution in prescribing >120 mg morphine-equivalent dose per day for patients not showing clinically meaningful improvement in pain and function. We report on opioid dosing in the WA Medicaid fee-for-service population for 273,200 adults with a paid claim for an opioid prescription between April 1, 2006 and December 31, 2010. Linear regression was used to test for trends in dosing over that time period, with quarter-year as the independent variable and median daily dose as the dependent variable. Prescription opioid use among WA Medicaid adults peaked in 2009, as evidenced by the unique number of opioid users (105,232), the total number of prescriptions (556,712), and the total person-years of prescription opioid use (29,442). Median opioid dose was unchanged from 2006 to 2010 at 37.5 mg morphine-equivalent dose, but doses at the 75th, 90th, 95th, and 99th percentiles declined significantly (P < .001). These results suggest that opioid treatment guidelines with dosing guidance may be able to reduce high-dose opioid use without affecting the median dose used. ⋯ Some fear that opioid dosing guidelines might restrict access to opioid therapy for patients who could benefit. However, there is evidence that high-dose opioid therapy entails significant risks without demonstrated benefit. These findings indicate that high-dose opioid therapy can be reduced without altering median opioid dose in a Medicaid population.
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The purpose of this study was to identify neural correlates of pain anticipation in people with nonspecific low back pain (NSLBP) that correlated with pain-related distress and disability, thus providing evidence for mechanisms underlying pain behavior in this population. Thirty NSLBP sufferers, with either high levels of pain behavior or low levels on the basis of Waddell signs, were scanned with functional magnetic resonance imaging while a straight-leg raise (of the side deemed to cause moderate pain in the lower back) was performed. On each trial colored stimuli were presented and used to indicate when the leg definitely would be raised (green; 100% certainty), might be raised (yellow; 50% certainty), or would definitely not be raised (red; 100% certainty). In response to expected versus unexpected pain the group difference in activation between patients with high levels of pain behavior and low levels of pain behavior covaried as a function of anxiety scores in the right insula and pregenual anterior cingulate cortex and as a function of catastrophizing in prefrontal and parietal cortex and hippocampus. The results suggest NSLBP populations with the highest levels of pain-related distress are more likely to attend to and infer threat from innocuous cues, which may contribute to the maintenance of pain behavior associated with some chronic pain states. ⋯ This article shows a likely neural network for exacerbating pain anticipation in NSLBP contributing to high levels of pain behavior in some people. This information could potentially help clinicians and patients to understand how anticipation of pain may contribute to patient pain and disability.
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Review
The Pain Experience of Hispanic Americans: A Critical Literature Review and Conceptual Model.
Although the Hispanic population is a burgeoning ethnic group in the United States, little is known about their pain-related experience. To address this gap, we critically reviewed the existing literature on pain experience and management among Hispanic Americans (HAs). We focused our review on the literature on nonmalignant pain, pain behaviors, and pain treatment seeking among HAs. Pain management experiences were examined from HA patients' and health care providers' perspectives. Our literature search included variations of the term "Hispanic" with "AND pain" in PubMed, Embase, Web of Science, ScienceDirect, and PsycINFO databases. A total of 117 studies met our inclusion criteria. We organized the results into a conceptual model with separate categories for biological and/or psychological and sociocultural and/or systems-level influences on HAs' pain experience, response to pain, and seeking and receiving pain care. We also included information on health care providers' experience of treating HA patients with pain. For each category, we identified future areas of research. We conclude with a discussion of limitations and clinical implications. ⋯ In this critical review of the literature we examined the pain and management experiences of the HA population. We propose a conceptual model, which highlights findings from the existing literature and future areas of research.