Noradrenaline inhibits substantia gelatinosa neurons in mice trigeminal subnucleus caudalis via α2 and β 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 α2 adrenergic agonist, clonidine (18/28, 64%) and the β adrenergic agonist, isoproterenol (9/24, 38%). NA-induced hyperpolarizing effect was also blocked by the α2 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 α1 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, GABAA and glycine receptor antagonists, respectively, indicating that the effects of NA are direct on the postsynaptic SG neurons. These results indicate that α2 and β adrenoceptor mediate inhibition, and α1 adrenoceptor mediates facilitation of orofacial nociceptive processing in mouse trigeminal brainstem SG neurons by postsynaptic actions.