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Bispebjerg Hospital - a part of Copenhagen University Hospital

The effects of long-term opioid treatment on the immune system in chronic non-cancer pain patients: A systematic review

Research output: Contribution to journalReviewpeer-review


  • P D K Diasso
  • H Birke
  • S D Nielsen
  • K M Main
  • J Højsted
  • P Sjøgren
  • G P Kurita
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Background and objective: Opioids have been increasingly prescribed for chronic non-cancer pain (CNCP). An association between long-term opioid treatment (L-TOT) of CNCP patients and suppression of both the innate and the adaptive immune system has been proposed. This systematic review aims at investigating the effects of L-TOT on the immune system in CNCP patients. Databases and data treatment: A systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the CINAHL for relevant articles was performed. Studies examining measures of both the innate and the adaptive immune system in adult CNCP patients in L-TOT (≥4 weeks of intake) were included. Outcomes and the level of evidence were analysed. Results: A total of 382 studies were identified; however, 376 were excluded (352 inappropriate methodology, 21 duplicates, three full-text could not be obtained) and one randomized controlled trial (RCT) and five cross-sectional studies were included and analysed. L-TOT compared with no treatment was associated with a lower percentage of natural killer (NK) cells, a lower absolute number of CD56 bright NK cells, a higher absolute number of IL-2-activated NK cells and a higher concentration of IL-1β as a response to toll-like receptor (TLR) agonists stimulation (Pam3CSK4, LPS, Imiquimod). No other significant differences were reported. Generalizability of the results was limited due to inconsistency of outcomes and an overall low quality of the studies. Conclusions: L-TOT may alter the immune system in CNCP patients, but the level of evidence is still weak. More studies are needed to clarify the impact of L-TOT on immune system function. Significance: This systematic review found indication that long-term opioid treatment alters the immune system in chronic non-cancer pain patients. These alterations involved the NK cells and IL-1β production. However, the level of evidence is weak.

Original languageEnglish
JournalEuropean journal of pain
Issue number3
Pages (from-to)481-496
Number of pages16
Publication statusPublished - Mar 2020

    Research areas

  • Adult, Analgesics, Opioid/therapeutic use, Cancer Pain, Chronic Pain/drug therapy, Humans, Immune System

ID: 58341919