Orofacial Pain Neurobiology in Sickle Cell Disease Patients in Nigeria: A Translational Investigation of Central Sensitization Mechanisms

Orofacial pain is a frequently reported but poorly characterized symptom among patients with sickle cell disease (SCD) in Nigeria, the country with the highest global SCD burden. The pathophysiology of orofacial pain in SCD is complex, potentially involving ischemic bone pain from vaso-occlusion, pulpal necrosis from sickling in dental microvasculature, and central sensitization mechanisms that amplify pain perception beyond the primary injury site. This translational PhD study investigates the neurobiology of orofacial pain in SCD patients attending hematology and maxillofacial surgery clinics at UCH Ibadan, LUTH Lagos, and UNTH Enugu, representing the South West and South East geopolitical zones. The study integrates three analytical levels: clinical quantitative sensory testing (QST) to characterize peripheral and central sensitization, neuroimaging using functional MRI to assess pain processing network activation patterns, and serum and cerebrospinal fluid analysis of neuropeptide biomarkers including substance P, calcitonin gene-related peptide (CGRP), and brain-derived neurotrophic factor (BDNF). Sixty adult SCD patients with chronic orofacial pain, 30 SCD patients without orofacial pain, and 30 healthy controls were recruited. QST results demonstrate significantly lowered pressure pain thresholds and enhanced temporal summation in SCD orofacial pain patients compared to both control groups, indicating central sensitization. Serum CGRP and BDNF were significantly elevated in the SCD orofacial pain group and correlated with clinical pain intensity scores. These findings provide the first neurobiological characterization of orofacial pain in Nigerian SCD patients and propose CGRP as a potential therapeutic target. Keywords: sickle cell disease, orofacial pain, central sensitization, CGRP, Nigeria.