Norepinephrine Plays an Important Role in Antinociceptive Modulation of Hypothalamic Paraventricular Nucleus in the Rat

ABSTRACT

Our previous study has proven that hypothalamic paraventricular nucleus (PVN) plays a role in antinociception. The effects of studied classical neurotransmitter on PVN antinociceptive modulation were investigated in the rat. The results showed: (1) Pain stimulation increased norepinephrine (NE), but not epinephrine, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DA metabolic product), homovanilic acid (DA metabolic product), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HT metabolic product), acetycholine (Ach), choline (Ach metabolic product), γ-aminobutyric acid (GABA), and L-glutamate acid concentrations in the PVN perfusion liquid; (2) PVN stimulation with L-glutamate sodium, which excited local neurons only, did not influence the concentrations of the studied classical neurotransmitter and metabolic product in the PVN perfusion liquid; (3) Microinjection of NE, epinephrine, or L-glutamate sodium into the PVN elevated pain threshold, and local administration of GABA decreased pain threshold in a dose-dependent manner, but PVN administration of Ach, DA, or 5-HT did not change pain threshold; (4) Microinjection of phentolamine (α-receptor antagonist) or MK801 [NMDA-receptor antagonist] into the PVN reduced pain threshold, and local administration of bicuculline (GABA-receptor antagonist) raised pain threshold, but PVN administration of propranolol (β-receptor antagonist), atropine (Muscarinic cholinergic receptor antagonist), 6-OH gallamine (Nicotinic cholinergic receptor antagonist), fluperidol (DA-receptor antagonist), or cyproheptadine (5-HT-receptor antagonist) did not alter pain threshold. The data suggested that endogenous NE, not epinephrine, 5-HT, Ach, GABA, and L-glutamate acid played an important role in the PVN antinociceptive modulation.

KEYWORDS: :

• antinociception
• α-Receptor
• hypothalamic paraventricular nucleus
• neurotransmitter
• norepinephrine
• rat