| The International Association for the Study of Pain(IASP)defines pain as "an unpleasant sensory and emotional experience associated with,or similar to,actual or potential tissue damage".It can happen anywhere in your body and can interfere with your daily activities,such as working,having a social life and taking care of yourself or others.It can lead to depression,anxiety and trouble sleeping,which can make your pain worse.This response creates a cycle that’s difficult to break.Common methods such as medication and surgical intervention can relieve pain to some extent,but they also have limitations,such as being addictive or invasive.Non-invasive high-frequency r TMS with M1 and DLPFC as the main targets has been confirmed to have certain effects on chronic pain,but it still lacks lasting analgesic effect,and the neural plasticity mechanism related to r TMS analgesia has not yet been clarified.The research in this thesis will combine electromyogram,electroencephalogram and transcranial magnetic stimulation to study the optimal pulse number and frequency of high-frequency r TMS pain relief,and explore the neuroplastic mechanism of r TMS analgesia.This thesis focuses on the research direction of the analgesic effect of high-frequency r TMS(HFr TMS)and its neuroplasticity,and carried out my research tasks in the master’s degree in two stages.The task of the first stage(Research one)is to clarify and effectively r TMS intervention paradigm.Based on the conclusions drawn from the research one,we applied the most effective stimulation paradigm to a second stage(Research two)to explore changes in neuroplasticity for r TMS analgesia.Research one: we performed a single-blind,sham-controlled,crossover study to investigate the influence of pulse number and frequency on r TMS analgesia in a single session.Using cold pain threshold,we directly compared the analgesic efficacy of 3000 pulses with 1500 pulses of 10 Hz r TMS over the M1 region.We also explored the analgesic influence of 3000 pulses of 20 Hz r TMS.Before and after r TMS,we also assessed motorevoked potential(MEP)amplitude for single pulse stimulation and longinterval cortical inhibition(LICI),to assess the impact of the differing r TMS doses on corticospinal excitability and GABAB mediated cortical inhibition.Research two: Using TMS-EEG techniques,we explored local and distributed neuroplastic changes associated with DLPFC analgesia.This is also a single-blind,sham-controlled,cross-over design study of healthy people.Participants were assessed with a cold pain task as well as single-pulse DLPFC-TMS before and after r TMS to assess changes in neuroplasticity and their correlation with changes in pain.The results showed that:(1)Only 10 Hz r TMS with 1500 pulses induced analgesic effects in healthy individuals subjected to cold pain,whereas 10 and 20 Hz stimulation with 3000 pulses had no effect.Changes in pain threshold(Post-Pre)in the three stimulation conditions were positively correlated with each other.Change in singlepulse cortical excitability(Post-Pre)was significantly correlated in the 10 Hz conditions,but not between 10 and 20 Hz conditions.(2)DLPFC analgesia is associated with a smaller N120 amplitude in the contralateral prefrontal cortex as well as with a larger N120 peak in the ipsilateral insular cortex.Furthermore,there was a strong negative correlation between N120 changes of these two regions whereby the amplitude changes of this dyad were associated with increased pain threshold.In addition,DLPFC stimulation enhanced coherence between the prefrontal and somatosensory cortices oscillating in the gamma frequency.Overall,our data present novel evidence on local and distributed neuroplastic changes associated with DLPFC analgesia. |
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