title: An obligatory role for spinal cholinergic neurons in the antiallodynic effects of clonidine after peripheral nerve injury.
abstract: BACKGROUND
  Indirect evidence supports a role of spinal cholinergic neurons in tonically reducing response to noxious mechanical stimulation and in effecting analgesia from alpha2-adrenergic agonists. This study directly assessed the role of cholinergic neurons in regulating the level of mechanical allodynia and in participating in the antiallodynic effect of the clinically used alpha2-adrenergic agonist, clonidine, in an animal model of neuropathic pain.
  
  
  METHODS
  Allodynia was produced in rats by ligation of the left L5 and L6 spinal nerves. Rats received a single intrathecal injection of saline or one of three different doses of the cholinergic neurotoxin, ethylcholine mustard aziridinium ion (AF64-A; 2, 5, and 15 nmol). Seven days later, allodynia was assessed before and after intrathecal injection of 15 microg clonidine. The spinal cord was removed, and spinal cord acetylcholine content, cholinergic neuron number and distribution, and alpha2-adrenergic receptor expression were determined.
  
  
  RESULTS
  AF64-A administration reduced both the number of cholinergic cells and the acetylcholine content of the lumbar dorsal spinal cord by 20-50% but did not affect level of mechanical allodynia. AF64-A did, however, completely block the anti-allodynic effect of clonidine. AF64-A did not reduce alpha2-adrenergic ligand binding in dorsal lumbar cord.
  
  
  CONCLUSIONS
  These data suggest that spinal cholinergic tone does not affect the level of mechanical allodynia after peripheral nerve injury. There is a quantitative reliance on spinal cholinergic neurons in the allodynia relieving properties of intrathecal clonidine, and this reliance does not depend on alpha2-adrenergic receptors colocalized on spinal cholinergic interneurons.
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: X
authors.initials: X
authors.lastname: Paqueron
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Bantel
authors.forename: J R
authors.initials: JR
authors.lastname: Tobin
authors.forename: M L
authors.initials: ML
authors.lastname: Voytko
authors.forename: J C
authors.initials: JC
authors.lastname: Eisenach
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001388:Aziridines / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D002794:Choline / Q000031:analogs & derivatives / Q000633:toxicity; D003000:Clonidine / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D059348:Peripheral Nerve Injuries; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D015016:Yohimbine / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018712:Analgesics, Non-Narcotic; D001388:Aziridines; D009498:Neurotoxins; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; C044894:ethylcholine aziridinium; D003000:Clonidine; D002794:Choline; D000109:Acetylcholine