Involvement of Melanocortin Receptors (MC3R, MC4R and MC5R) and Cyclooxygenases (COX-1/2) in the Painful Crisis of Sickle Cell Disease in Brazzaville

Introduction: Sickle cell disease is an autosomal recessive inherited hemoglobinopathy characterized by a point mutation in the HBB gene, leading to the substitution of valine for glutamic acid in position 6 of the β-globin chain (Glu6Val), and the formation of an abnormal hemoglobin, hemoglobin S (HbS). CVO is the most frequent and disabling clinical manifestation of sickle cell disease, representing the main cause of hospitalization, school or work absenteeism, and reduced quality of life in SS homozygous patients. Despite therapeutic advances, management of CVO-related pain remains limited and unsatisfactory, particularly in sub-Saharan Africa. Commonly used treatments include opioids (such as morphine), which are effective in the short term but are associated with significant side effects, including tolerance, constipation, sedation, and, above all, the risk of dependence and abuse. These therapeutic limitations underscore the pressing need to develop new, targeted approaches that are more effective and better tolerated, based on an in-depth understanding of the pathophysiological mechanisms of sickle cell pain. With this in mind, melanocortin receptors (MCRs) and cyclooxygenases (COX-1 and COX-2), biomarkers involved in inflammation and/or pain, respectively, were investigated in this study. For the first time in the Congolese context, our study aims to investigate the involvement of MCRs (MC3R, MC4R, and MC5R) and cyclooxygenases in the onset of pain in homozygous sickle cell patients monitored in Brazzaville. This approach aims to identify relevant prognostic biomarkers, gain a better understanding of the molecular mechanisms underlying inflammatory pain, and open up prospects for innovative targeted therapies in a public health context with a high unmet therapeutic need. Methodology: A prospective observational study was carried out on 85 patients (2 - 62 years). Pain intensity was assessed using a validated scale. Biomarkers GR, GB, PLT, CRP, IL-6, COX-1, COX-2, MC3R, MCR4R and MC5R were measured by turbidimetry and ELISA. This study received ethics committee approval (CRSSA). Data were analyzed statistically using specific tools. Results: 45.88% or 39 of patients were in CVO, while severe pain was reported frequently in more than 14 patients during attacks. WBC, CRP, COX-2, VCAM-1 and MC5R showed significantly higher concentrations during CVO (p = 0.018 for WBC; p Conclusion: Our study highlighted the problem of the involvement of MCRs and cyclooxygenases as inflammatory biomarkers associated with pain in CVO in homozygous sickle cell patients in the inter-critical and critical phases. In conclusion, our results show the involvement of COX-2 and MC5R as anti-inflammatory targets and CRP as a biomarker associated with inflammation and pain in CVO in homozygous sickle cell patients.