Erythrocyte cAMP in Determining Frequency of Acute Pain Episodes in Sickle Cell Disease Patients from Odisha State, India

Abstract

Vaso-occlusive crisis (VOC) occurs more frequently during stress in sickle cell disease patients. Epinephrine released during stress increases adhesion of sickled red blood cells (RBCs) to endothelium and to leukocytes, a process mediated through erythrocyte cyclic adenosine monophosphate (cAMP). Increased adhesion of sickled RBCs retards blood flow through the capillaries and promotes vaso-occlusion. Therefore, we examined the association of RBC-cAMP levels with frequency of acute pain episodes in sickle cell disease subjects. Using a case control study design, we measured RBC-cAMP levels, fetal hemoglobin (Hb F), α-thalassemia (α-thal) and other hematological parameters at baseline (sham treated) and after stimulation with epinephrine. The cases consisted of sickle cell disease subjects with three or more acute pain episodes in the last 12 months, and those without a single acute pain episode in the last 12 months were considered as controls. Significantly higher cAMP values were found in cases than the controls, in both sham treated (p < 0.001) and epinephrine treated RBCs (p < 0.001) by Wilcoxon Rank Sum test. However, significant association of cAMP values was observed both on univariate [odds ratio (OR): 4.8, 95% confidence interval (95% CI): 1.51-15.19, p < 0.008) and multivariate logistic regression analyses only in epinephrine treated (OR: 5.07, 95% CI: 1.53-16.82, p < 0.008) but not in sham-treated RBCs. In the covariates, Hb F consistently showed protective effects in univariate as well as in multivariate analyses. Frequent acute pain episodes are associated with higher cAMP levels than those with less frequent pain episodes, only after stimulation with epinephrine but not with baseline level.

Keywords:

• Acute pain episodes
• cyclic adenosine monophosphate (cAMP)
• epinephrine
• sickle cell disease
• vaso-occlusive crisis (VOC)

Acknowledgments

We would like to express our appreciation for the support from study participants, and hospital nurses for assisting in this project. P. Das was involved in designing the study and conceptualizing the manuscript; P.K. Mohanty, K. Das, S. Patel, S. Meher and B.P. Jit were involved in recruitment of cases and controls; B.P. Jit, A. Pradhan, P. Purohit, J.R. Mohanty and S. Sinha collected the data and performed the laboratory work; P. Das conducted the data analysis; P.K. Mohanty, P. Purohit, S. Patel, S. Meher, K. Das and R.K. Behera provided insightful comments in the review of the manuscript. All authors contributed intellectual input during the study period and contributed to redrafting the manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

The study was partly supported by the Ministry of Science and Technology, Department of Biotechnology, Government of India funding (Project Number: BT/Bio-CARe/07/551/2012). The funding agencies had no involvement in study design, data collection, data analysis, and data interpretation.