Neurophysiology of Pain Sensitisation in Sickle Cell Disease: Spinal and Supraspinal Mechanisms Underlying Chronic Pain Transition in Patients at the Lagos University Teaching Hospital

Background: Chronic pain in sickle cell disease represents a transition from episodic vaso-occlusive crisis pain to persistent pain mediated by central sensitisation involving spinal dorsal horn hyperexcitability and supraspinal modulatory pathway dysfunction. Understanding the neurophysiology of this transition is critical for developing non-opioid pain management strategies relevant to the Nigerian context, where opioid access is highly restricted. Objectives: This study aims to characterise conditioned pain modulation efficiency, temporal summation of pain, and pressure pain thresholds as measures of central sensitisation in sickle cell disease patients with and without chronic pain phenotypes, and to examine somatosensory cortex excitability by transcranial magnetic stimulation, plasma substance P, beta-endorphin, and calcitonin gene-related peptide concentrations at Lagos University Teaching Hospital. Methods: Forty sickle cell disease patients with chronic pain, forty without chronic pain, and twenty healthy haemoglobin AA controls will be recruited. Conditioned pain modulation and temporal summation will be assessed using established heat and pressure paradigms. Single-pulse transcranial magnetic stimulation will characterise motor cortex excitability as a proxy for cortical pain modulation. Neuropeptide quantification will use multiplexed immunoassay. Structural equation modelling will test the hypothesised pathway from peripheral haemolytic burden through spinal sensitisation to supraspinal dysmodulation. Expected Outcomes: Chronic pain sickle cell patients are hypothesised to demonstrate impaired conditioned pain modulation, enhanced temporal summation, and elevated substance P alongside reduced beta-endorphin compared to episodic-only and control groups. Conclusion: Findings will establish the neurophysiological basis for multimodal, non-opioid pain management approaches for sickle cell disease in Nigeria. Keywords: central sensitisation, sickle cell disease, chronic pain, conditioned pain modulation, Lagos.