Objective:Chronic neuropathic pain has a high prevalence.As a kind of persistent pain,it has a long-term impact on the life and work of patients.Most traditional analgesics have little effect on neuropathic pain,so it has been a difficult medical problem in clinical practice.However,electroencephalogram(EEG)signal analysis is an approach that can realize real-time detection of chronic pain.Therefore,it is of great significance to carry out EEG signal analysis and processing for chronic pain.This project aims to decode the EEG signals in the process of chronic pain in the hope of providing potential therapeutic methods for the treatment of chronic pain in clinical practice.Methods:The dual-channel electrodes of the two brain regions were designed and implanted into the hippocampus and anterior cingulate gyrus of mice.The EEG signals of mice were recorded at 1d before CCI and 3d,7d,14 d,21d,28 d,35d,42 d,49d and 56 d after CCI respectively.We used chronic constriction injury(CCI)in mice as a neuropathic pain model.Behavioral observation and GFAP immunofluorescence staining of spinal dorsal horn were used to confirm the success of the procedure.Mechanical pain and thermal-sensitive pain of injured paw were detected 1d before CCI surgery and 3d,7d,14 d,21d,28 d,35d,42 d,49d and 56 d after surgery.MATLAB and Neuroexplorer software were used to analyze the EEG signals and explore the correlation between the signals in the dual-channel cross-brain region.The power spectral density(PSD)of the single channel was analyzed first,and then the amplitude-amplitude coupling(AAC)and phase-amplitude coupling(PAC)of the two channels were analyzed to find the characteristic rhythm.The characteristic rhythm was quantified to analyze the changes of characteristic events in the process of chronic pain.The time domain of characteristic events is analyzed to explore the timing of events.According to EEG,EMG and motion parameters,sleep analysis was carried out to analyze the changes of sleep state during the modeling process and detect the relationship between characteristic events and sleep state.Results:1)The immunofluorescence intensity of the spinal dorsal horn in the CCI group was significantly different from that in the sham group,indicating that the modeling was successful.The results of nissl staining showed that the electrode filaments were located in the CA1 area of the hippocampus and the anterior cingulate gyrus.2)The mechanical pain threshold of mice in CCI group decreased continuously from 14 days to 56 days after surgery,and the difference with Sham was statistically significant(P<0.05).The thermal pain threshold was lower at each time point from 3 days to 56 days after surgery than before surgery,with statistical difference compared with Sham group.3)The PSD of ripple frequency band(100-200Hz)in CCI group was significantly reduced,and the number of ripple was also significantly reduced after quantification,reaching the minimum at day 21.PAC figure shows that ripple(hippocampus)is correlated with delta(anterior cingulate gyrus),delta(anterior cingulate gyrus)is correlated with spindle(anterior cingulate gyrus).The time domain diagram shows that the time sequence relation is ripple-delta-spindle.On the 21 d after CCI surgery,compared with Sham group,the number of ripple-delta was significantly decreased and the number of ripple-delta-spindle was significantly decreased.There was no significant difference in sleep staging before and after CCI modeling,and the incidence of ripple and its coupling events in slow wave sleep stage was as high as 80%.Conclusion:In the development of chronic pain,there is a decrease in the frequency of hippocampal ripple and the coupling between hippocampal ripple and anterior cingulate delta-spindle.The results suggest that the intervention of nerve oscillations between the anterior cingulate gyrus and hippocampus may regulate the perception of chronic pain. |