Microinjections of norepinephrine within the superficial laminae of trigeminal subnucleus caudalis evoke increases in plasma adrenocorticotropin in the rat

To determine if local release of norepinephrine within the medullary dorsal horn influences autonomic responses often associated with nociception, microinjections of norepinephrine or of specific adrenergic receptor agonists were directed at the trigeminal subnucleus caudalis (Vc) in pentobarbital-anesthetized rats. Norepinephrine (20 nmol, 100 nl) evoked a significant increase (+233.8 ± 89.5 pg/ml, P < 0.01) in plasma concentrations of adrenocorticotropin (ACTH) after injections withinthe superficial laminae (I-II) of Vc, whereas mean arterial pressure or heart rate were not affected. Methoxamine (20 nmol), an α₁-adrenoceptor agonist, injections into laminae I-II also increased plasma ACTH (+90.6 ± 32 pg/ml, P < 0.025) without affecting arterial pressure or heart rate. Norepinephrine injections into the deeper laminae (III-V) of Vc caused a variable increase in plasma ACTH (+203.5± 146.5 pg/ml, P < 0.01) that was not mimicked by injections of methoxamine. Microinjections of α₂-(clonidine) or β-(isoproterenol) adrenergic receptor agonists into Vc had no effect on plasma ACTH regardless of the laminar site of injection. The results suggest that norepinephrine acts within Vc to alter selected autonomic responses often associated with nociception. The involvement of an α₁-adrenergic receptor subtype within the superficial laminae of the medullary dorsal horn suggests a neural mechanism for norepinephrine-evoked increase in plasma ACTH that is distinct from the well known α₂-adrenergic receptor-mediated antinociceptive effects of norepinephrine.