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

Abstract

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 (P=0.041) and B cells (P=0.005), even after adjustment for a number of clinical treatment factors (P=0.006 and P=0.052, respectively). On the day that more patients were able to communicate, Fas on B cells (r=0.897, P=0.029) and cytotoxic T cells (r=0.832; P=0.037) associated with NRS ratings. Associations between pain ratings and ACTH serum levels were noted (P<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 (P=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.

Keywords:

• lymphocyte apoptosis
• pain
• critical illness
• adrenocorticotropic hormone
• cortisol
• substance P

Acknowledgments

This work is part of a larger study on the role of stress in critical illness, preliminary results of which have been published in Papathanassoglou ED, Mpouzika MD, Giannakopoulou M, Bozas E, Middleton N, Boti S, Karabinis A. Pilot Investigation of the Association Between Serum Stress Neuropeptide Levels and Lymphocyte Expression of Fas and Fas Ligand in Critical Illness. Biol Res Nurs 2015;17(3):285–294; Mpouzika MD, Papathanassoglou ED, Giannakopoulou M, Bozas E, Middleton N, Boti S, Patiraki EI, Karabinis A. Altered serum stress neuropeptide levels in critically ill individuals and associations with lymphocyte populations. Neuropeptides 2013;47(1):25–36. This study was supported by the Cyprus University of Technology Faculty Grant to EDEP and by the National and Kapodistrian University of Athens ELKE Grants 70/4/5688 and 70/4/6403 to EDEP and MG, respectively.

Disclosure

The authors report no conflicts of interest in this work.