title: Alpha 2 adrenoceptor-mediated presynaptic inhibition of primary afferent glutamatergic transmission in rat substantia gelatinosa neurons.
abstract: BACKGROUND
  Although intrathecal administration of norepinephrine is known to produce analgesia, cellular mechanisms for this action have not yet been fully understood.
  
  
  METHODS
  The actions of norepinephrine (50 microm) on glutamatergic transmission were examined by using the whole cell patch clamp technique in substantia gelatinosa neurons of an adult rat spinal cord slice with an attached dorsal root.
  
  
  RESULTS
  Norepinephrine inhibited the amplitude of monosynaptically evoked A delta-fiber and C-fiber excitatory postsynaptic currents in a reversible manner. When compared in magnitude between the A delta-fiber and C-fiber excitatory postsynaptic currents, the former inhibition (50 +/- 4%, n = 20) was significantly larger than the latter one (28 +/- 4%, n = 8). Both actions of norepinephrine were mimicked by an alpha2 adrenoceptor agonist, clonidine (10 microm), and an alpha 2A agonist, oxymetazoline (10 microm), but not by an alpha1 agonist, phenylephrine (10 microm), and a beta agonist, isoproterenol (40 microm). The inhibitory actions were antagonized by an alpha 2 antagonist, yohimbine (1 microm), all of the results of which indicate an involvement of alpha 2 adrenoceptors. Norepinephrine did not affect the amplitude of miniature excitatory postsynaptic current and of a response of substantia gelatinosa neurons to AMPA, indicating that its action on evoked excitatory postsynaptic currents is presynaptic in origin.
  
  
  CONCLUSIONS
  Norepinephrine inhibits A delta-fiber- and C-fiber-mediated sensory transmission to substantia gelatinosa neurons through the activation of the alpha 2 adrenoceptor (possibly alpha2A type, based on the current, published behavioral and anatomical data) existing in primary afferent terminals; this action of norepinephrine is more effective in A delta-fiber than C-fiber transmission. This could contribute to at least a part of inhibitory modulation of pain sensation in the substantia gelatinosa by intrathecally administered norepinephrine.
authors.affiliation: Department of Physiology, Saga Medical School, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kumamoto
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Furue
authors.forename: Megumu
authors.initials: M
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013376:Substantia Gelatinosa / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D018341:Receptors, Adrenergic, alpha-2; D018698:Glutamic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D009638:Norepinephrine