Higher pain scores, similar opioid doses and side effects associated with antipyretic analgesics in specialised tertiary pain care

Lötsch, Jörn; Freynhagen, Rainer; Hentig, Nils von; Grießinger, Norbert; Zimmermann, Michael; Sittl, Reinhard; Geißlinger, Gerd

doi:10.1007/s00011-010-0215-3

Cited by 6 publications

(2 citation statements)

References 19 publications

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“…In a cross-sectional study in pain patients by Lötsch et al, the use of opioids was associated with lower pain scores compared to non-users [28]. Surprisingly, use of non-opioid antipyretic analgesics alone, including NSAIDs and paracetamol, was associated with higher pain scores, leading the authors to hypothesize that long-term cyclooxygenase inhibition may have counter-analgesic effects [28]. Although this finding needs confirmation from prospective studies, this opens the possibility that paradoxically increased levels of pain are not confined to the use of opioids.…”

Section: Discussionmentioning

confidence: 99%

Pain sensitivity and analgesic use among 10,486 adults: the Tromsø study

Samuelsen

Nielsen

Wilsgaard

et al. 2017

BMC Pharmacol Toxicol

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BackgroundIncreased pain sensitivity is a putative risk factor for chronic pain and consequently for analgesic use. Conversely, analgesic use may be a cause of increased pain sensitivity, e.g., through opioid-induced hyperalgesia. We aimed to study the association between pain sensitivity and analgesic use in a general population, and to test the hypothesis that increased baseline pain sensitivity is a risk factor for future persistent analgesic use.MethodsThe Tromsø Study (2007–08), a population-based health study, was linked with eight years of prescription data from the Norwegian Prescription Database. The cold pressor test was completed in 10,486 participants aged 30+ years, and we used cold pressor endurance time as a proxy measure of pain sensitivity. Cross-sectional associations with different measures of analgesic use were assessed. Furthermore, a cohort of 9,657 persons was followed for 4.5 years.ResultsIn the cross-sectional analysis, increased pain sensitivity was associated with analgesic use; regular users of opioids alone were more pain sensitive than regular users of non-opioid analgesics. Increased baseline pain sensitivity was a risk factor for persistent analgesic use, i.e., using non-steroidal anti-inflammatory drugs, paracetamol, or opioids for ≥ 90 days and proportion-of-days-covered ≥ 40% (HR = 1.22, 95% CI 1.06-1.40), although not statistical significant after confounder adjustment.ConclusionsIncreased pain sensitivity was associated with analgesic use in general, and reduced pain tolerance was found for both opioid and non-opioid analgesic users. The data suggest that hyperalgesia is an effect of analgesics, whereas pain tolerance has little impact on future analgesic use.Electronic supplementary materialThe online version of this article (doi:10.1186/s40360-017-0149-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Pain sensitivity and analgesic use among 10,486 adults: the Tromsø study

Samuelsen

Nielsen

Wilsgaard

et al. 2017

BMC Pharmacol Toxicol

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“…DNA from whole blood samples and opioid-related phenotypes was available from previous studies [ 40 – 42 ]. Cohort 1 consisted of 83 (26 men, 57 women, aged 39.6 ± 7.02) healthy subjects that were drawn randomly from a control cohort.…”

Section: Methodsmentioning

confidence: 99%

Disagreement between two common biomarkers of global DNA methylation

et al. 2016

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BackgroundThe quantification of global DNA methylation has been established in epigenetic screening. As more practicable alternatives to the HPLC-based gold standard, the methylation analysis of CpG islands in repeatable elements (LINE-1) and the luminometric methylation assay (LUMA) of overall 5-methylcytosine content in “CCGG” recognition sites are most widely used. Both methods are applied as virtually equivalent, despite the hints that their results only partly agree. This triggered the present agreement assessments.ResultsThree different human cell types (cultured MCF7 and SHSY5Y cell lines treated with different chemical modulators of DNA methylation and whole blood drawn from pain patients and healthy volunteers) were submitted to the global DNA methylation assays employing LINE-1 or LUMA-based pyrosequencing measurements. The agreement between the two bioassays was assessed using generally accepted approaches to the statistics for laboratory method comparison studies. Although global DNA methylation levels measured by the two methods correlated, five different lines of statistical evidence consistently rejected the assumption of complete agreement. Specifically, a bias was observed between the two methods. In addition, both the magnitude and direction of bias were tissue-dependent. Interassay differences could be grouped based on Bayesian statistics, and these groups allowed in turn to re-identify the originating tissue.ConclusionsAlthough providing partly correlated measurements of DNA methylation, interchangeability of the quantitative results obtained with LINE-1 and LUMA was jeopardized by a consistent bias between the results. Moreover, the present analyses strongly indicate a tissue specificity of the differences between the two methods.

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Chronic opioid use is associated with increased DNA methylation correlating with increased clinical pain

Doehring

Oertel

Sittl

et al. 2013

Pain

143

137

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Environmentally caused changes in chromosomes that do not alter the DNA sequence but cause phenotypic changes by altering gene transcription are summarized as epigenetics. A major epigenetic mechanism is methylation or demethylation at CpG-rich DNA islands. DNA methylation triggered by drugs has largely unexplored therapeutic consequences. Here we report increased methylation at a CpG rich island in the OPRM1 gene coding for μ-opioid receptors and at a global methylation site (LINE-1) in leukocytes of methadone-substituted former opiate addicts compared with matched healthy controls. Higher DNA methylation associated with chronic opioid exposure was reproduced in an independent cohort of opioid-treated as compared to non-opioid-treated pain patients. This suggests that opioids may stimulate DNA methylation. The OPRM1 methylation had no immediate effect on μ-opioid receptor transcription and was not associated with opioid dosing requirements. However, the global DNA methylation at LINE-1 was significantly correlated with increased chronic pain. This suggests inhibitory effects on the transcription of still unspecified nocifensive gene products. It further implies that opioids may be causally associated with increased genome-wide DNA methylation, although currently there is no direct evidence of this. This has phenotypic consequences for pain and may provide a new, epigenetics-associated mechanism of opioid-induced hyperalgesia. The results indicate a potential influence of opioid analgesics on the patients' epigenome. They emphasize the need for reliable and cost-effective screening tools and may imply that high-throughput screening for lead compounds in artificial expression systems may not provide the best tools for identifying new pain medications.

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Higher pain scores, similar opioid doses and side effects associated with antipyretic analgesics in specialised tertiary pain care

Cited by 6 publications

References 19 publications

Pain sensitivity and analgesic use among 10,486 adults: the Tromsø study

Pain sensitivity and analgesic use among 10,486 adults: the Tromsø study

Disagreement between two common biomarkers of global DNA methylation

Chronic opioid use is associated with increased DNA methylation correlating with increased clinical pain

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