Association between lymphocyte expression of the apoptotic receptor Fas and pain in critically ill patients.

Objective: Lymphocyte apoptosis in critical illness is associated with immunosuppression. We explored for the first time the associations between pain ratings and expression of the apoptotic receptor Fas on B and T cells in critically ill patients and the potential mediating effects of adrenocorticotropic hormone (ACTH), cortisol, and substance P (SP).

Design: This is an exploratory correlational study with repeated measurements (14 days followup) and cross-sectional comparisons.

Setting: This study was conducted in a state hospital in the metropolitan area of Athens, Greece.

Participants: The participants were 36 consecutive critically ill patients and 36 matched controls.

Outcome Measures: Pain measured by the self-reported numeric rating scale [NRS], the behavioral pain scale, and the pain assessment scale was the primary outcome measure. Flow cytometry (Fas), electrochemiluminescence (ACTH and cortisol) and enzyme-linked immunosorbent assay (SP) were used. Mixed linear models for repeated measurements and bivariable associations at discrete time points were employed.

Results: Significant pain at rest was noted. Pain ratings associated with Fas expression on cytotoxic T cells (=0.041) and B cells (=0.005), even after adjustment for a number of clinical treatment factors (=0.006 and =0.052, respectively). On the day that more patients were able to communicate, Fas on B cells (=0.897, =0.029) and cytotoxic T cells (=0.832; =0.037) associated with NRS ratings. Associations between pain ratings and ACTH serum levels were noted (<0.05). When stress neuropeptide levels were added to the model, the statistical significance of the associations between pain ratings and Fas expression was attenuated (=0.052-0.063), suggesting that stress neuropeptides may partially mediate the association.

Conclusion: Preliminary evidence for the association between pain and lymphocyte apoptotic susceptibility is provided. The role of pain management in maintaining immunocompetence in critical illness is worth exploring.