Cytotoxic activity and subset populations of peripheral blood natural killer cells in patients with chronic pain

Background: Chronic pain reportedly exerts complex effects on immune function. Natural killer (NK) cells are lymphocytes that play a critical role in cellular and innate immunity. This study examined changes in the subset populations and cytotoxic activity of peripheral blood NK cells in patients with chronic pain. Methods: Thirty patients with chronic moderate-to-severe pain (group P) and age-matched pain-free subjects (group NoP) were enrolled. Peripheral whole blood was analyzed for the percentage and expression of NK cell surface markers (CD56 and CD16) by flow cytometry. Cytotoxic activity was assayed by evaluating CD69 expression on CD3(-)/CD56(+) NK cells. Results: The percentage of NK cells among total lymphocytes was not significantly different between groups P and NoP (16.3 +/- 9.3 vs. 20.2 +/- 10.5%). Likewise, the percentages of two major NK cell subsets, CD56(bright) and CD56(dim), were also not significantly different between the two groups. However, the percentage of CD56(bright)/CD16(+) subset, was slightly but significantly increased in group P (1.0 +/- 0.9%; P < 0.01) compared with group NoP (0.5 +/- 0.6%). The cytotoxicity of NK cells was not different between the two groups, showing similar CD69 expression (P vs. NoP = 29.2 +/- 15.2 vs. 32.0 +/- 15.0%). These findings were not influenced by pain intensity, opioid use, or disease causing pain in group P. Conclusions: NK cell cytotoxic activity and major subset populations, with the exception of an increased percentage of the CD56(bright)/CD16(+) subset, are not significantly altered in patients with chronic severe pain.