Neurophysiology of Pain Modulation in Chronic Sickle Cell Disease: Endogenous Opioid System Dysfunction and Implications for Pain Management in South East Nigeria

Chronic pain in sickle cell disease is a poorly understood phenomenon that may involve central sensitisation and endogenous opioid system dysregulation, mechanisms that have not been examined in African sickle cell populations and whose characterisation could transform pain management approaches. This study investigated neurophysiological mechanisms of pain modulation, specifically endogenous opioid system function and central sensitisation, in adults with chronic sickle cell disease-related pain in South East Nigeria, making an original mechanistic contribution. A case-control design enrolled 70 sickle cell disease patients with chronic pain based on the American Pain Society chronic pain criteria and 35 sickle cell disease patients without chronic pain, alongside 35 healthy haemoglobin AA controls. Conditioned pain modulation efficiency was measured by pressure algometry as an index of endogenous pain inhibitory function. Temporal summation of pain assessed central sensitisation. Plasma beta-endorphin and met-enkephalin concentrations were measured by radioimmunoassay. Functional connectivity of descending pain modulatory pathways was estimated from resting-state EEG coherence between frontal and somatosensory regions. Mixed ANOVA, mediation analysis, and correlation approaches were applied. Results showed significantly impaired conditioned pain modulation in chronic pain patients compared to both other groups. Beta-endorphin levels were reduced in chronic pain patients, and temporal summation was amplified, confirming central sensitisation. Frontal-somatosensory EEG coherence was reduced, suggesting descending pathway hypofunction. This study makes an original neurophysiological contribution to sickle cell pain science. Opioid system-targeted and central sensitisation-directed pain therapies are proposed. Keywords: sickle cell pain, endogenous opioids, central sensitisation, conditioned pain modulation, South East Nigeria.