TY - JOUR

T1 - The effects of long-term opioid treatment on the immune system in chronic non-cancer pain patients

T2 - A systematic review

AU - Diasso, Pernille D K

AU - Birke, Hanne

AU - Nielsen, Susanne D

AU - Main, Katharina M

AU - Højsted, Jette

AU - Sjøgren, Per

AU - Kurita, Geana P

N1 - © 2019 European Pain Federation - EFIC®.

PY - 2020

Y1 - 2020

N2 - 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 CD56bright 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.

AB - 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 CD56bright 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.

U2 - 10.1002/ejp.1506

DO - 10.1002/ejp.1506

M3 - Review

C2 - 31705699

VL - 24

SP - 481

EP - 496

JO - European Journal of Pain

JF - European Journal of Pain

SN - 1090-3801

IS - 3

ER -