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Topical morphine gel in the treatment of painful leg ulcers, a double-blind, placebo-controlled clinical trial: a pilot study
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
2012 (English)In: International Wound Journal, ISSN 1742-4801, E-ISSN 1742-481X, Vol. 9, no 4, 419-427 p.Article in journal (Refereed) Published
Abstract [en]

Chronic painful wounds, a major health problem, have a detrimental impact on the quality of life due to associated pain. Some clinical reports have suggested that local administration of morphine could be beneficial. The aim of this study was to evaluate the analgesic effect of topically applied morphine on chronic painful leg ulcers. Twenty-one patients were randomly assigned to receive either morphine or placebo in a randomised, placebo-controlled, crossover pilot study. Each patient was treated four times in total. Pain was measured by the visual analogue score (VAS) before application of gel, directly after and after 2, 6, 12 and 24 hours. Although an overall, clinically relevant, reduction of pain was observed upon treatment with morphine, the difference was not statistically significant. Morphine reduced pain scores more than placebo on treatment occasions 1 and 2. The difference was statistically significant only 2 hours after dressing on the first treatment occasion. Thus, our study did not demonstrate a consistent and globally significant difference in nociception in patients treated with morphine. However, the relatively small number of patients included in our study and other methodological limitations makes it difficult for us to draw general conclusions regarding efficacy of topically applied morphine as an effective treatment for some painful ulcers. Further studies are warranted to evaluate the value of topically applied morphine in the treatment of patients with chronic painful leg ulcers.

Place, publisher, year, edition, pages
Blackwell Publishing, 2012. Vol. 9, no 4, 419-427 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-75512DOI: 10.1111/j.1742-481X.2011.00901.xISI: 000306406000011PubMedID: 22151619OAI: oai:DiVA.org:liu-75512DiVA: diva2:507607
Available from: 2012-03-05 Created: 2012-03-05 Last updated: 2017-12-07
In thesis
1. Practical and clinical use of opioids
Open this publication in new window or tab >>Practical and clinical use of opioids
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pain is a common symptom of a number of conditions including cancer and one of the most frequent reasons for seeking healthcare. Acute and chronic pain result in considerable discomfort with a detrimental impact on the quality of life. Opioids are the mainstay of pain management for many patients with severe pain. Opioids are, unfortunately, also commonly abused drugs, and are well-represented in forensic toxicology investigations.

Side effects related to the central nervous system are the major reasons fordiscontinuation of opioid treatment. In this thesis, we tested the hypothesis that local analgesic treatment by opioids, without the usual opioid-related side effects, could be a potential alternative to systemic opioid treatment. We examined the analgesic effect of topically applied morphine in a randomized, double blind, cross over study in patients with painful leg ulcers. Significant reduction of pain was obtained after application of both morphine and placebo gel. Morphine reduced pain more than placebo but the difference was not statistically significant. However, morphine could reduce pain considerably more than placebo in those cases where VAS (Visual analog scale) was higher initially.

Another issue with opioid therapy is the substantial individual variability in response to opioids including morphine and tramadol. We investigated the significance of UGT2B7, CYP2D6, OPRM1 and ABCB1 polymorphisms for pharmacokinetic and pharmacodynamic properties of morphine and tramadol. We showed that genetic variants in CYP2D6 and UGT2B7 have an important role in the metabolism of tramadol and morphine respectively. While the role of SNPs in ABCB1 remained unclear, genetic variants in OPRM1 gene were correlated with the required dose of morphine. Taken together, these findings suggest that genotypes should be taken into consideration when interpreting clinical pharmacology and forensic toxicology results.

Opioids, besides their analgesic properties, have other pharmacological effects including effects on immune system. We evaluated potential differences between commonly used opiates with regard to their effect on the immune system. We found an inhibition of cytokine release, in the order of potency as follows: tramadol > ketobemidone >morphine >fentanyl. All opioids with the exception of fentanyl were capable of inhibiting production of mRNAs for TNF-alpha and IL-8. Further studies are needed to understand the clinical implications of the observed immunosuppressive effects of opioids and to improve opioid treatment strategies in patients with cancer.

Here, we have found that individual genotype matters and affects the individual response. Further research is warranted to tailor individualized treatment. Personalized medicine has increased in importance and will hopefully in the near future become standard procedure to improve and predict the outcome of treatment by opioids.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 72 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1364
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-96795 (URN)978-91-7519-603-9 (ISBN)
Public defence
2013-09-13, Berzeliussalen,, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Note

The series name in the title page is incorret. The correct title should be Linköping University Medical Dissertations.

Available from: 2013-08-27 Created: 2013-08-27 Last updated: 2014-06-05Bibliographically approved

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Bastami, SalumehFrödin, ThomasAhlner, JohanUppugunduri, Srinivas

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Clinical PharmacologyFaculty of Health SciencesDermatology and VenerologyDepartment of Dermatology and Venerology in ÖstergötlandClinical ChemistryDepartment of Clinical Chemistry
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