Pain sensitization in peripheral entrapment neuropathy and associated neuroplasticity by multimodal functional magnetic resonance imaging

Abstract

Caused by median nerve compression, carpal tunnel syndrome (CTS) is the most prevalent peripheral entrapment neuropathy. Characterized by sensory symptoms including pain, numbness, and tingling and motor deficits like muscle wasting and weakness, CTS has undermined individuals’ functional abilities and quality of life. Moreover, abnormal pain sensitization was observed in CTS patients, presenting with widespread pain distribution and pain hypersensitivity. Central sensitization has been shown to be associated with poor response to treatments and unsatisfactory prognosis. Although the self-reported Central Sensitization Inventory (CSI) is a popular tool to screen central sensitization, a valid Chinese version of the CSI is still lacking. Besides, the characteristics of patient-reported neuropathic pain and pain sensitization contours in Chinese populations with CTS remain not fully understood, due to the inconsistency and heterogeneity in previous literature. Furthermore, the underlying cortical plasticity mechanisms associated with the centrally mediating pain processing in CTS patients are not clear hitherto. Therefore, this thesis, comprised of three studies, aimed to i) translate the original English CSI into Chinese with a cultural validation and to conduct a psychometric validation among the Chinese population with chronic pain; ii) delineate the clinical features of neuropathic pain and central sensitization in the Chinese population with CTS, and identify potential predictors associated with the pain sensitization; iii) investigate the potential underlying brain plasticity associated with CTS, using multimodal functional magnetic resonance imaging. First of all, this thesis produced the Chinese CSI through forward translation, backward translation, expert panel, and piloting. The Chinese CSI generated was then validated among 419 participants with chronic pain. Our results confirmed the excellent test-retest reliability and internal consistency (Intraclass correlation coefficient=0.932, Cronbach’s alpha =0.9) and good criterion and construct validities of the Chinese CSI. Furthermore, 155 CTS patients and 57 normal controls were enrolled to examine the neuropathic pain and pain sensitization profiles in CTS and the associated risk factors. Of the CTS participants, over 60% presented a sign of clinical central sensitization by CSI, more than 70% were determined as potential or very likely neuropathic pain, and around one quarter had anxiety or depression. Anxiety was found a risk factor associated with central sensitization in CTS (adjusted OR =1.31, 95% CI 1.08-1.59). With regard to the brain plasticity changes related with the central pain processing in CTS, significantly decreased cerebral blood flow and maladaptive functional brain connectivity were demonstrated in brain regions involving sensory, affective, and cognitive processing. There were significant associations between the cortical plasticity alterations (cerebral blood flow and functional connectivity) and clinical outcomes (symptom severity, pain sensitization, pain intensity, anxiety, depression, and general health) in the CTS patients. In conclusion, this thesis provides a validated Chinese CSI to measure central sensitization and presents a picture of neuropathic pain and pain sensitization profiles in CTS patients as well as the associated predictors. More importantly, the thesis adds insightful evidence in the CTS-associated central pain processing mechanisms by disclosing new neuroimaging biomarkers, which thereby facilitates optimal treatments targeting cortical regions in a multi-disciplinary approach for CTS.