Noradrenaline inhibits substantia gelatinosa neurons in mice trigeminal subnucleus caudalis via alpha(2) and beta adrenoceptors.

The actions of noradrenaline (NA) in the substantia gelatinosa (SG) are important for their antinociceptive effects. In order to identify the possible mechanisms underlying NA actions in the SG of trigeminal subnucleus caudalis (Vc), the direct membrane effects were examined by gramicidin-perforated patch clamp recording using brain slice preparation from immature mice brainstem. The majority (60/71, 85%) of neurons tested were hyperpolarized by NA application, and these hyperpolarizing effects were mimicked both by the alpha(2) adrenergic agonist, clonidine (18/28, 64%) and the beta adrenergic agonist, isoproterenol (9/24, 38%). NA-induced hyperpolarizing effect was also blocked by the alpha(2) adrenergic antagonist, yohimbine in five out of six neurons tested. However, a minority (5/71, 7%) of neurons tested were depolarized by NA, and these depolarizing effects were mimicked by the alpha(1) adrenergic agonist, phenylephrine (11/26, 42%). NA-induced hyperpolarizing effects were maintained in the presence of tetrodotoxin (TTX), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), d,l-2-amino-5-phosphonopentanoic acid (AP5), picrotoxin and strychnine, a Na(+) channel, ionotropic glutamate receptor, GABA(A) and glycine receptor antagonists, respectively, indicating that the effects of NA are direct on the postsynaptic SG neurons. These results indicate that alpha(2) and beta adrenoceptor mediate inhibition, and alpha(1) adrenoceptor mediates facilitation of orofacial nociceptive processing in mouse trigeminal brainstem SG neurons by postsynaptic actions.