title: A ¹⁸F-fluorodeoxyglucose MicroPET imaging study to assess changes in brain glucose metabolism in a rat model of surgery-induced latent pain sensitization.
abstract: BACKGROUND
  Neuroplastic changes involved in latent pain sensitization after surgery are poorly defined. We assessed temporal changes in glucose brain metabolism in a postoperative rat model using positron emission tomography. We also investigated brain metabolism after naloxone administration.
  
  
  METHODS
  Rats were given remifentanil anesthetic and underwent a plantar incision, with 1 mg/kg of (-)-naloxone subcutaneously administered on postoperative days 20 and 21. Using the von Frey test, mechanical thresholds were measured pre- and postoperatively at different time points in awake animals during F-fluorodeoxyglucose (F-FDG) uptake. Brain images were also obtained the day before mechanical testing, using a positron emission tomography R4 scanner (Concorde Microsystems, Siemens, Knoxville, TN). Differences in brain activity were assessed utilizing a statistical parametric mapping.
  
  
  RESULTS
  Surgery induced minor changes in F-FDG uptake in the cerebellum, hippocampus, and posterior cortex, which extended to the thalamus, hypothalamus, and brainstem on days 6 and 7. Changes were still present on day 21. Maximal postoperative hypersensitivity was observed on day 2. The administration of (-)-naloxone on day 21 induced significant hypersensitivity, greatly enhancing the effect on F-FDG uptake. In sham-operated rats, naloxone induced changes limited to the striatum and the cerebellum. Nonnociceptive stimulation with von Frey filaments had no effect on F-FDG uptake.
  
  
  CONCLUSIONS
  Surgery, remifentanil, and their combination induced long-lasting and significant metabolic changes in the pain brain matrix, with a positive correlation with hypersensitivity after naloxone. Changes in brain F-FDG precipitated by naloxone suggest that surgery under remifentanil anesthetic induces the greatest neuroplastic brain adaptations in opioid-related pathways involved in nociceptive processing and long-lasting pain sensitization.
authors.affiliation: Grup de Recerca en Fisiopatologia i Tractament del Dolor, Programa de Neurociències, Department of Anesthesiology, Institut Municipal d'Investigació Mèdica, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Asunción
authors.initials: A
authors.lastname: Romero
authors.forename: Santiago
authors.initials: S
authors.lastname: Rojas
authors.forename: David
authors.initials: D
authors.lastname: Cabañero
authors.forename: Juan D
authors.initials: JD
authors.lastname: Gispert
authors.forename: José R
authors.initials: JR
authors.lastname: Herance
authors.forename: Ana
authors.initials: A
authors.lastname: Campillo
authors.forename: Margarita M
authors.initials: MM
authors.lastname: Puig
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold; D010880:Piperidines / Q000494:pharmacology; D049268:Positron-Emission Tomography; D011183:Postoperative Complications / Q000503:physiopathology*; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077208:Remifentanil
chemical_list: D010880:Piperidines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D009270:Naloxone; D005947:Glucose; D000077208:Remifentanil