| Summary: | 博士 === 國立臺灣大學 === 生命科學系 === 105 === Pain is an unpleasant sensory and emotional experiences associated with actual or potential tissue damage, excessive and chronic pain harmful to the quality of life. Chronic pain is a major health problem which affects up to 20% of the general population. Although acute pain patients can be properly managed, most of the chronic pain patients fail to achieve adequate pain relief. Among the most difficult ones are the neuropathic pain patients. Neuropathic pain is initiated by a primary lesion or dysfunction in the nervous system, and often causes chronic pain. It had been known that peripheral nerve damage induced early onset of ectopic discharge in injured nerve fibers. We hypothesized that peripheral nerve injury also induces sustained activation in the forebrain, and these brain areas eventually develop plasticity changes involved in chronic neuropathic pain. In this dissertation, we aimed to identify the sustained activation and the plasticity changes of forebrain during the development of Spared Nerve Injury (SNI) induced neuropathic pain via multiple magnetic resonance imaging (MRI) and electrophysiological recording approaches.
First, we aim to longitudinally monitor the synaptic connectivity of the specific thalamocortical pathway via dexmedetomidine-based blood oxygen level dependent functional MRI (BOLD-fMRI) protocol. In this study, a pairs of tungsten electrodes, which caused acceptable susceptibility artifact limited around the electrodes, were used to target the ventroposterior thalamus – primary somatosensory (VP-S1) pathway. We discovered reproducible frequency- and amplitude-dependent BOLD responses in the ipsilateral S1. The S1 BOLD responses during the 2 sessions (one week apart) were conserved in response amplitude, area size, and location.
In the second part, we combined the BOLD-fMRI and manganese-enhanced MRI (MEMRI) to monitor the brain activation during three different neuropathic pain development stages, including the brain activation at the moment of nerve injury detected using BOLD-fMRI, and the brain activity during the 1st and the 8th day using MEMRI. We observed tonic activation in bilateral insular cortices and contralateral S1 immediately after the SNI, and these areas established long-term abnormal functional connectivities. By using the electrophysiological and DBS-fMRI approach, we found the primary injured VP-S1 pathway and surrounding VP-S1 pathway established different thalamocortical plasticity after the SNI, whereas the rostral anterior insular and the anterior cingulate cortex, which have large and diffusive receptive field, showed consistent enhanced thalamocortical connection after the SNI.
By combination of multiple approaches, we not only provided an integrated result of functional brain changes after peripheral neuropathy, but also demonstrated an example framework to study the brain plasticity by combining multiple fMRI methods that complement each other.
|
|---|
