Osteonecrosis of the femoral head (ONFH), also known as avascular or ischemic necrosis of femoral head, is a hip disorder and challenging orthopedic disease that severely diminishes patient quality of life. The risk factors of ONFH are varied and include physical trauma, smoking, excessive alcohol consumption, autoimmune diseases, coagulation disorders, hemoglobinopathies, corticosteroid therapy and other factors1. ONFH is a progressive pathological process characterized by ischemia, necrosis, and eventually collapse. Despite no predominant pattern of a clinical presentation, pain and dysfunction of the joint seem occur frequently in ONFH2. Pain presents in only half of patients with no limitation of activity in the early stages but almost always appears in later stages2. The disease generally progresses to collapse and eventually painful osteoarthritis if symptomatic ONFH has not been treated3. The treatment strategy of ONFH depends on the disease stage. Reducing pain is one of the main goals of early treatment4. Total hip arthroplasty (THA) in patients with osteonecrosis is widely used to improve patient quality of life. However, revision surgeries after THA in young patients are common, and thigh pain is a common complaint after THA5. This pain is a primary factor influencing patients’ dissatisfaction after THA6.
As observed in ONFH, joint diseases cause pain, and the impaired joints and surrounding muscles, ligaments and tendons can cause proprioception abnormalities. Such abnormal sensory perception leads to the remodeling of the sensory cortex. The mature human primary somatosensory cortex can reorganize itself in response to changes in sensory input, displaying strong plasticity capacity. Following the elimination of afferent return, there is a well-known ‘invasion’ of the deafferented region of the brain by the cortical representation zones of still-intact portions of the brain adjacent to it7. Human and animal studies have confirmed that sensory deprivation can induce somatotopic map plasticity in the primary somatosensory cortex7, 8. Prolonged and chronic pain can both alter neural plasticity at the cortical level9. It has gradually been recognized that cerebral processes contribute to pain beyond the level of nociceptive input and contact behavioral and psychological influences10. Pain is a complex sensory and emotional experience that is shaped by psychobiology, expectations from past and learned pain experiences and attention processes11. In a study of intestinal diseases related to abdominal pain, researchers found altered neural modulation of pain in affective and cognitive brain regions, including the cingulate cortex12. Brain regions of headache patients showed significant activations in areas responsible for the processing of cognitive empathy13. Current theories describe the brain activity of pain as abnormal functioning in large-scale networks that include non-nociceptive regions14, 15. Chronic cervical spondylotic pain, chronic back pain and knee osteoarthritis show functional anomaly during the pain process16, 17. Subjects with cruciate ligament deficiency also exhibit increased activation in the secondary somatosensory area (where pain and sensory processing occur)18.
The remodeling of somatosensory cortex evidences the plasticity of the somatotopic map 19. Recently, somatosensory cortex stimulation has been proposed as a possible treatment for deafferentation pain after amputation20. Exploring the map plasticity in patients with ONFH can provide insight into its possible treatment. Therefore, based on previous studies that have discovered abnormal brain activity in many kinds of diseases related to sensory abnormality, we hypothesized that ONFH with pain may induce somatotopic map plasticity in cortex and yield a characteristic pattern of brain neural activity. Volume-based normalization may introduce inaccuracies in anatomical positioning of functional data21, 22, and it is difficult to account for inter-subject variability in gyrus size, shape or position in a 3D referential; furthermore, such differences may correspond to the displacement of a functional focus to a different gyrus in some subjects22. As a large part of the data originates from the cortex, methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study.
Diverse approaches can be used to detect map plasticity, including genetics analysis, synaptic and in vivo physiology analysis, optical imaging, and ultrastructural analysis19. Although these methods show excellent validity and reliability, they are not simple or convenient to use in the human body. An article published in the New England Journal of Medicine reported increased activity in the stable patterns across regions that are associated with experimentally induced acute pain and tonic pain in healthy people. They proposed that a functional magnetic resonance imaging (fMRI) could be used to assess pain 23. Resting-state functional magnetic resonance imaging rs-fMRI (rs-fMRI), as a convenient and noninvasive method, has been widely used in the evaluation of central remodeling in various diseases related to pain. Therefore, in our study, we chose fMRI as the assessment tool to test our hypothesis. To comprehensively understand the characteristics of somatotopic map plasticity in patients with ONFH, an understanding of the roles of pain-related brain regions and functional connections is needed. Therefore, among several functional measures of fMRI, surface-based regional homogeneity (ReHo)24 and seed-based functional connectivity (FC)25 were chosen to analyze localized and remote changes in brain functions. Compared with 3D ReHo, surface-based ReHo has higher test-retest reliability and can more clearly reveal the intrinsic functional organization of cortex26, which could be extremely useful for integrating various measures of both the structure and function of the cortical surface27. Cortical thickness and the volume of subcortical gray nuclei were also analyzed in the study.