title: Disruption of Spinal Noradrenergic Activation Delays Recovery of Acute Incision-Induced Hypersensitivity and Increases Spinal Glial Activation in the Rat.
abstract: Results of clinical studies suggest that descending inhibitory controls from the brainstem are important for speeding recovery from pain after surgery. We examined the effects of destroying spinally projecting noradrenergic neurons via intrathecally administered antibody to dopamine β-hydroxylase conjugated to saporin (DβH-saporin) on recovery in an acute incisional pain model. Mechanical and thermal paw withdrawal thresholds and nonevoked spontaneous guarding scores were tested for several weeks postoperatively and analyzed using mixed effects growth curve modeling. DβH-saporin treatment resulted in a significant prolongation in the duration of mechanical and to a lesser degree thermal hypersensitivity in the ipsilateral paw of incised rats but did not increase the duration of spontaneous guarding. DβH-saporin treatment was also associated with increased microglial and astrocyte activation in the ipsilateral spinal cord 21 days after incision compared with immunoglobulin G-saporin treated controls. Chronic intrathecal administration of the α2 adrenergic receptor antagonist atipamezole (50-200 μg/d) produced similar effects. These data suggest that spinally projecting noradrenergic pathways and spinal α2 adrenergic receptor activation are important for speeding recovery from hypersensitivity after surgical incision possibly by reducing spinal glial activation. Interventions that augment the noradrenergic system might be important to speed recovery from pain after surgery.
  
  
  CONCLUSIONS
  Endogenous descending spinal noradrenergic activation promotes resolution of incision-induced hypersensitivity and inhibits spinal microglial and astrocyte activation in part through α2 adrenergic receptors.
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Vipin
authors.initials: V
authors.lastname: Arora
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Morado-Urbina
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Aschenbrenner
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Hayashida
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: FuZhou
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Martin
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina; Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: James C
authors.initials: JC
authors.lastname: Eisenach
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina. Electronic address: chrpeter@wfubmc.edu.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Peters
mesh_terms: D059331:Adrenergic Neurons / Q000187:drug effects / Q000378:metabolism*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D010149:Postoperative Pain / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; C050701:atipamezole
keywords: Descending inhibition; chronification; glial plasticity; growth curve; postoperative pain