Influencing Factors Of Phantom Limb Pain After Amputation Of Malignant Tumors And The Predictive Efficacy Of Related Brain Imaging Changes

Objective: Phantom limb pain(PLP)is currently defined as a neuropathic pain,and its mechanism of occurrence and development is still unclear.In previous studies,the PLP caused by malignant amputation was not discussed separately.In order to further investigate the epidemiological status,risk factors and pathogenesis of PLP in this specific population,resting-state functional magnetic resonance imaging(rs-f MRI)will be used as a research method to study the related mechanism of “pain memory hypothesis” on the occurrence of acute PLP in the first month after amputation.Methods: Retrospective study was conducted by collected data from 2013 in Liaoning Cancer Hospital.In addition to basic demographic characteristics,preoperative pain,preoperative chemotherapy,pathological diagnosis,and amputation level were collected.The significant was set at p<0.05,when discussing the difference of PLP occurrence for two age incidence peak and two amputation extremities.Further prospective investigation of preoperative pain characteristics(including pain intensity,duration,and neuropathic characteristics)on the occurrence of PLP within one month after amputation was analyzed.Degree centrality(DC)from rs-f MRI data was extracted for the discussion of differences and relevance of functional imaging on the occurrence of PLP and pre-operative pain.Numerical rating scale(NRS)was used for calculating the severity of pain,and DN4 score was used for determining the neuropathologic characteristic of pain.The influence of perioperative emotional state(Acute Stress Scale,Hamilton Depression and Anxiety Scale)on the occurrence of PLP within one month after surgery was evaluated ether.Taking the occurrence of PLP after the operation as the grouping standard,the differences of DC in preoperative f MRI data between two groups were compared,the DC-different areas were determined,and the DC value of each area was extracted to analyze whether the DC-changes were related to the preoperative pain characteristics or emotional state.Finally,factor analysis was used to determine which relevant areas were the main influencing factors,then they will be extracted and modeled as independent variables,and included in the final model to predict the severity of postoperative PLP.Hierarchical regression was used for the assessment of incremental prediction.Results: From 2013 to 2020,a total of 162 adult amputation cases was collected.Within one month after amputation,the incidence of PLP was 54.3%,the incidence of phantom limb sensation(PLS)was 65.4%,and the incidence of residual limb pain(RLP)was 32.7%.Among the groups of whether PLP occurred,the factors that were significantly different included "amputation level" and "preoperative pain".A further subgroup test showed that patients whose amputation level was below the wrist and ankle joints,and who had not experienced long preoperative pain had a significantly reduced incidence of PLP.After binary logistics regression analysis,it is found that the level of amputation is the primary risk factor for PLP.Comparing the difference between upper and lower limbs amputees,the incidence of PLS is significantly higher after lower limb amputation,but there is no significant difference in the occurrence of PLP and RLP.In order to compare age factors,121 cases of malignant amputation of the main lower limbs were screened again,and it was found that within one month after the amputation,76.2%of adult patients and 87.9% of young patients(<25 years old)experienced PLP.The incidence of PLP in adults is related to the duration of preoperative pain.Adolescents have a higher proportion of pre-amputation pain and preoperative chemotherapy,but they are not significantly related to the occurrence of PLP.No other factors had a significant influence on PLP.Based on the above statistical results,only 44 adult cases of bone tumors who underwent the proximal amputation of the lower limbs were prospectively investigated to verify the pain memory hypothesis.Through the difference analysis,it was found that the neuropathic characteristics of preoperative pain(DN4 scale score ?4),and the intensity of preoperative pain are risks for the occurrence of acute PLP(p<0.05).In addition,perioperative anxiety is also a risk factor.No other factors were significantly related to the occurrence of acute PLP.Comparing the preoperative DC between groups,it was found that compared with the PLPgroup,there were 7 main brain areas with significant DC differences in the PLP+ group,including preoperative DC-descending in left precuneus lobe,left posterior cingulate gyrus,right central anterior gyrus;DC-ascending in left anterior cingulate gyrus,left middle orbitofrontal gyrus,right occipital middle gyrus,right superior orbitofrontal gyrus.Through correlation analysis,it was found that the DC value of the left anterior cuneiform lobe was negatively correlated with the preoperative pain NRS score and DN4 score.The DC values of right middle occipital gyrus,left anterior cingulate gyrus,left middle orbitofrontal gyrus,right superior orbitofrontal gyrus was positively correlated with preoperative pain DN4 score,preoperative anxiety,and NRS of postoperative pain.Further adding suspicious related brain areas to the hierarchical regression model,the addition of the corresponding DC value index can bring a 26.7% increase in prediction of the severity of postoperative PLP,and make the prediction efficiency of the final model reach 81.1%.The final regression coefficients included: DC value of posterior cingulate gyrus(= 0.488,p<0.01),DC value of right superior orbitofrontal gyrus(= 0.792,p<0.01),DC value of left middle orbitofrontal gyrus(= 0.477,p<0.01).Conclusion: The incidence of phantom limb pain is high after amputation of malignant tumors.Through a combination of retrospective and prospective studies,combined with functional imaging changes,the influencing factors of phantom limb pain within one month after surgery were analyzed and predicted.It was found that preoperative pain and perioperative anxiety may affect the postoperative PLP,and the addition of preoperative functional brain imaging indicators is expected to become a more reliable tool for predicting the severity of PLP in the early postoperative period by carrying the mentioned pain and psychological characteristics.Facing the current dilemma in the treatment of PLP,researches on prevention strategies based on functional brain imaging,more attention paid on prevention than therapy,may be the future development direction of PLP control.