The Metabolic Material Basis Of Transition From Acute To Chronic Post-surgical Pain

With the advancement of precise medical care and considering the tremendous negative impact of untreated pain on quality of life for people,there is a lack of objective measures to determine treatment options and appropriateness for pain,as well as the potential for serious addiction of existing opioid pain drugs.At the same time,with the development of bio-markers,bio-markers have become an irreplaceable and important means of disease diagnosis and important targets of precise analgesics.Therefore,we intend to use metabonomics and non-targeted screening of potential key substances for the transition from acute to chronic pain after surgery,so as to lay the foundation for accurate evaluation and effective intervention of post-operative pain.According to Brennett rat model of sciatic nerve constriction pain,rats were ligated with sciatic nerve in the left hind limb,and chronic constricted injury pain model was established.The paw of mechanical withdrawal threshold(MWT)of rats was recorded by Von Frey electronic pain meter.Metabolites in hypothalamus and spinal cord of 13 groups of rats were detected by GC-MS.Differential metabolites were mapped to KEGG database.Metabolic pathway enrichment was analyzed by MB-Role pathway analysis function and KEGG ID of differential metabolites.The results of behavioral observation showed that after sciatic nerve ligation,the activity of rats decreased significantly,the spontaneous lifting of injured limbs and the consumption of food decreased significantly,and the clinical symptoms such as licking,biting or shaking of surgical feet were avoided.Von Frey electronic pain meter showed that the threshold of mechanical withdrawal of left hind limb in the operation group was significantly lower than that before operation(P<0.05)at 1,3,5,7,14 and 21 days after operation,and was lower than 20% of the preoperative threshold.Based on the rat model of chronic constricted injury,244 different metabolites such as aspartic acid,lysine,N-acetylaspartic acid,pantothenic acid,isocitric acid and quinolinic acid were screened out from rat hypothalamus and spinal cord by using the metabolomic analysis method of GC-MS.A rat model of chronic constricted injury pain has been successfully established.Aspartic acid,glutamic acid,pantothenic acid,isocitric acid and quinolinic acid may be potential diagnostic markers for transition from acute to chronic postsurgical pain.