α2 adrenoceptor-mediated presynaptic inbibition of primary afferent glutamatergic transmission in rat substantia gelatinosa neurons

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 mum) 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 Adelta-fiber and C-fiber excitatory postsynaptic currents in a reversible manner. When compared in magnitude between the Adelta-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 alpha(2) adrenoceptor agonist, clonidine (10 muM), and an alpha(2A) agonist, oxymetazoline (10 mum), but not by an, a, agonist, phenylephrine (10 mum), and a beta agonist, isoproterenol (40 mum). The inhibitory actions were antagonized by an alpha(2) antagonist, yohimbine (1 muM), 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 Adelta-fiber- and C-fiber-mediated sensory transmission to substantia gelatinosa neurons through the activation of the alpha(2) adrenoceptor (possibly alpha(2A) type, based on the current, published behavioral and anatomical data) existing in primary afferent terminals; this action of norepinephrine is more effective in Adelta-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.