title: Depletion of endogenous noradrenaline does not prevent spinal cord plasticity following peripheral nerve injury.
abstract: The present study examined the role of endogenous noradrenaline on glial and neuronal plasticity in the spinal cord in rats after peripheral nerve injury. An intrathecal injection of dopamine-β-hydroxylase antibody conjugated to saporin (DβH-saporin) completely depleted noradrenergic axons in the spinal cord and also reduced noradrenergic neurons in the locus coeruleus (A6) and A5 noradrenergic nucleus in the brainstem and noradrenergic axons in the paraventricular nucleus of the hypothalamus. DβH-saporin treatment itself did not alter mechanical withdrawal threshold, but enhanced mechanical hypersensitivity and intrathecal clonidine analgesia after L5-L6 spinal nerve ligation. In the spinal dorsal horn of spinal nerve ligation rats, DβH-saporin treatment increased choline acetyltransferase immunoreactivity as well as immunoreactivity in microglia of ionized calcium binding adaptor molecule 1[IBA1] and in astrocytes of glial fibrillary acidic protein, and brain-derived nerve growth factor content. DβH-saporin treatment did not, however, alter the fractional release of acetylcholine from terminals by dexmedetomidine after nerve injury. These results suggest that endogenous tone of noradrenergic fibers is not necessary for the plasticity of α2-adrenoceptor analgesia and glial activation after nerve injury, but might play an inhibitory role on glial activation.
  
  
  CONCLUSIONS
  This study demonstrates that endogenous noradrenaline modulates plasticity of glia and cholinergic neurons in the spinal cord after peripheral nerve injury and hence influences the pathophysiology of spinal cord changes associated with neuropathic pain.
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Hayashida
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Peters
authors.forename: Silvia
authors.initials: S
authors.lastname: Gutierrez
authors.forename: James C
authors.initials: JC
authors.lastname: Eisenach
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001285:Atropine / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003000:Clonidine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism / Q000494:pharmacology; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000922:Immunotoxins / Q000494:pharmacology; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009638:Norepinephrine / Q000172:deficiency*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology; D000076985:Saporins; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D013127:Spinal Nerves / Q000503:physiopathology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014316:Tritium / Q000378:metabolism
chemical_list: D000759:Adjuvants, Anesthesia; C100745:Aif1 protein, rat; D000700:Analgesics; D019208:Brain-Derived Neurotrophic Factor; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D000922:Immunotoxins; D008840:Microfilament Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D014316:Tritium; D001285:Atropine; D004299:Dopamine beta-Hydroxylase; D002795:Choline O-Acetyltransferase; D000076985:Saporins; D003000:Clonidine; D000109:Acetylcholine; D009638:Norepinephrine