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

Diasso, P D K; Birke, H; Nielsen, S D; Main, K M; Højsted, J; Sjøgren, P; Kurita, G P

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 analyzed. RESULTS Three-hundred-eighty-two studies were identified; however, 376 were excluded (352 inappropriate methodology, 21 duplicates, 3 full-text could not be obtained) and one RCT and five cross-sectional studies were included and analyzed. L-TOT compared with no treatment was associated with a lower percentage of 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.