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The effects of long-term morphine oncbinding and functionality of different opioids in C-6 cells expressing the OPRM-1 receptor
Uppsala University, Disciplinary Domain of Medicine and Pharmacy. (Kirurgiska vetenskaper)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy. (Kirurgiska vetenskaper)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
Keyword [en]
lontg-term morphine, OPRM 1-receptor, receptor functionality, [35 S] GTPg-assay
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology
Identifiers
URN: urn:nbn:se:uu:diva-129619OAI: oai:DiVA.org:uu-129619DiVA: diva2:344557
Available from: 2010-08-19 Created: 2010-08-19 Last updated: 2011-01-14
In thesis
1. Long-term Effects of Opioids in the Treatment of Chronic Pain: Investigation of Problems and Hazards on Clinical, Biochemical, Cellular and Genetic Levels
Open this publication in new window or tab >>Long-term Effects of Opioids in the Treatment of Chronic Pain: Investigation of Problems and Hazards on Clinical, Biochemical, Cellular and Genetic Levels
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

After two decades of liberal prescribing of opioids, there has been an increasing recognition of problems connected to the prolonged use of opioids for chronic pain.

The aim of my thesis was to explore some consequences of long-term opioid treatment for chronic pain such as problematic opioid use, endocrine disorders, tolerance and genetic variations in pain and opioid response.

Sixty patients with severe pain and problematic opioid use were treated with a structured methadone programme. Risk factors were musculoskeletal pain, psychiatric co-morbidity and previous addiction. Treatment resulted in good pain relief and improved quality of life, but function was impaired by side effects indicating endocrine dysregulation.

The possibility of opioid-induced endocrine dysfunction was explored in the second paper, where 40 pain patients treated with strong opioids and 20 pain patients without treatment of strong opioids were investigated. The opioid-treated patients had significantly higher incidence of endocrine disturbance affecting gonadal and adrenal function and prolactin levels.

The functionality of the μ-receptor after long-term treatment with morphine, saline and naloxone was explored in a cell-line expressing the μ-receptor. After one and four weeks of treatment the binding was tested with morphine, methadone, fentanyl and DAMGO and function measured by GTP γ-assay. The binding of DAMGO was significantly diminished after 4 weeks in cells treated with morphine compared with saline and naloxone.

Genetic variation in three genes with functional impact on opioid response and pain sensitivity was investigated in 80 patients with chronic low-back pain and differential opioid sensitivity and in 56 healthy controls. The results indicated a higher incidence of opioid-related side effects and gender differences in patients with the minor allele of the ABCB1 gene, a correlation between increased opioid sensitivity and the major CACNA2D2 allele and a possible relationship between intrinsic protection against chronic pain and the minor allele of OPRM1.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 586
Keyword
opioid, chonic pain, long-term opioid treatment
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology
Identifiers
urn:nbn:se:uu:diva-129624 (URN)978-91-554-7866-7 (ISBN)
Public defence
2010-09-25, Auditorium minus, Gustavianum, Akademigatan 3, 753 10 Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2010-09-02 Created: 2010-08-19 Last updated: 2011-01-14Bibliographically approved

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