title: Paradoxical effect of noradrenaline-mediated neurotransmission in the antinociceptive phenomenon that accompanies tonic-clonic seizures: role of locus coeruleus neurons and α(2)- and β-noradrenergic receptors.
abstract: The postictal state is generally followed by antinociception. It is known that connections between the dorsal raphe nucleus, the periaqueductal gray matter, and the locus coeruleus, an important noradrenergic brainstem nucleus, are involved in the descending control of ascending nociceptive pathways. The aim of the present study was to determine whether noradrenergic mechanisms in the locus coeruleus are involved in postictal antinociception. Yohimbine (an α(2)-receptor antagonist) or propranolol (a β-receptor antagonist) was microinjected unilaterally into the locus coeruleus, followed by intraperitoneal administration of pentylenetetrazole (PTZ), a noncompetitive antagonist that blocks GABA-mediated Cl(-) influx. Although the administration of both yohimbine and propranolol to the locus coeruleus/subcoeruleus area resulted in a significant decrease in tonic or tonic-clonic seizure-induced antinociception, the effect of yohimbine restricted to the locus coeruleus was more distinct compared with that of propranolol, possibly because of the presynaptic localization of α(2)-noradrenergic receptors in locus coeruleus neurons. These effects were related to the modulation of noradrenergic activity in the locus coeruleus. Interestingly, microinjections of noradrenaline into the locus coeruleus also decrease the postictal antinociception. The present results suggest that the mechanism underlying postictal antinociception involves both α(2)- and β-noradrenergic receptors in the locus coeruleus, although the action of noradrenaline on these receptors causes a paradoxical effect, depending on the nature of the local neurotransmission.
authors.affiliation: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (SP), Brazil.
authors.forename: Tatiana Tocchini
authors.initials: TT
authors.lastname: Felippotti
authors.forename: Célio Marcos
authors.initials: CM
authors.lastname: dos Reis Ferreira
authors.forename: Renato Leonardo
authors.initials: RL
authors.lastname: de Freitas
authors.forename: Rithiele Cristina
authors.initials: RC
authors.lastname: de Oliveira
authors.forename: Ricardo
authors.initials: R
authors.lastname: de Oliveira
authors.forename: Tatiana
authors.initials: T
authors.lastname: Paschoalin-Maurin
authors.forename: Norberto Cysne
authors.initials: NC
authors.lastname: Coimbra
mesh_terms: D059331:Adrenergic Neurons / Q000187:drug effects*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004347:Drug Interactions; D008125:Locus Coeruleus / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008845:Microinjections; D009638:Norepinephrine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D010433:Pentylenetetrazole / Q000633:toxicity; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D011433:Propranolol; D010433:Pentylenetetrazole; D009638:Norepinephrine