Long-term intrathecal morphine and bupivacaine upregulate MOR gene expression in lymphocytes.
BACKGROUND
Several studies have shown that opioids may suppress the immune system either by binding to mu-opioid receptors (MOR) expressed in immune cells or by activating these receptors within the central nervous system.


OBJECTIVE
To assess the level of lymphocyte expression of MOR mRNA in patients with chronic non-cancer pain, who were treated with intrathecal morphine or with morphine plus bupivacaine via an intrathecal drug delivery system, and to investigate whether intrathecal morphine and the associated local anesthetic administration influences lymphocyte subpopulations.


METHODS
In total, 29 people [10 controls (age range 59-85 years) and 19 patients (age range 47-89 years) with various chronic non-malignant pain conditions] were enrolled in the study. MOR mRNA levels were evaluated in peripheral lymphocytes, and lymphocyte subsets were determined by direct immunofluorescence using flow cytometry.


RESULTS
After 12 months of treatment with intrathecal morphine (1.5-4 mg/day), there was an increase in MOR mRNA levels in lymphocytes of 65% compared with controls and 47% with pretreatment values. Even higher levels (increase of 142% compared with controls and 135% with pretreatment values) were observed in the patients treated with morphine plus bupivacaine (0.2-0.4 mg/day). Elevation of MOR mRNA levels was confirmed in patients after 24 months of treatment. At this time point, the percentage of natural killer cells was significantly decreased.


CONCLUSIONS
This preliminary study suggests that opioids must be used with care in patients who are already immunosuppressed by disease or by other, concurrently administered drugs.
Campana
Gabriele
G
Department of Pharmacology, University of Bologna, Italy.
Sarti
Donatella
D
Spampinato
Santi
S
Raffaeli
William
W
D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000779:Anesthetics, Local / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000187:drug effects*; D002045:Bupivacaine / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007278:Injections, Spinal; D007694:Killer Cells, Natural / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D015854:Up-Regulation
D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D017450:Receptors, Opioid, mu; D009020:Morphine; D002045:Bupivacaine