Preoperative Norepinephrine Levels in Cerebrospinal Fluid and Plasma of Pediatric Patients Predict Postoperative Pain Intensity after Spinal Fusion Surgery

Abstract

Introduction The purpose of the present study was to investigate if preoperative concentrations of monoamine neurotransmitters that are known to be involved in descending pain modulation are associated with perioperative pain intensity in a pediatric cohort of patients with idiopathic scoliosis scheduled for elective spinal fusion surgery. Material and Methods Patients scheduled to undergo spinal surgery for Adolescent Idiopathic Scoliosis (AIS) between the ages of 12 and 18 years were recruited from the outpatient clinic of the Shriners Hospital for Children ( n = 50). Plasmatic and cerebrospinal fluid concentrations of epinephrine (EPI), norepinephrine (NE), and their respective metabolite metanephrine (ME) and normetanephrine (NME), were assessed. Five mL of blood were collected for study analysis in an EDTA-coated collection tube after the anesthesia induction. Prior to the intratechal epimorphine injection, 2 mL of cerebrospinal fluid was collected in a low binding protein tube. Monoamine neurotransmitters were derivatized by reductive diethylation analyzed by liquid chromatography coupled with tandem mass spectrometry on TripleTOF 5600 mass spectrometer. At all time points throughout the study (preoperative, first postoperative 24 hours = postoperative day 1 (POD1), second 24 hours = postoperative day 2 (POD2) and postoperative 6 weeks follow-up visit), pain intensity was rated with the use of the Faces Pain Scale-Revised (FPS-R). Linear regressions were performed to assess the predictive role of catecholamine levels for postoperative pain. The Mann-Whitney-U test was used to assess differences in baseline characteristics between patients reporting presence of pain and pain-free patients as well as for all other comparisons other than correlations. Results Our results demonstrate that patients reporting persistent postsurgical pain 6 weeks after surgery have greater preoperative peripheral and/or central norepinephrine (NE) and normetanephrine levels when compared with patients reporting no pain at follow-up. Likewise, in the acute postoperative period, patients reporting moderate-to-severe pain intensity had higher preoperative central NE levels. Conclusion These results support the evidence for a potential role of catecholamine levels in predicting postoperative pain intensity and sympathetically maintained pain, which could place pediatric patients at risk for the development of chronic postsurgical pain. Incidence and severity of persistent postoperative pain may be reduced by specific NE preoperative interventions.