title: Decrease in the expression of N-methyl-D-aspartate receptors in the nucleus tractus solitarii induces antinociception and increases blood pressure.
abstract: N-methyl-D-aspartate receptors (NMDAR) have a role in cardiovascular control at the nucleus tractus solitarii (NTS), eliciting increases or decreases in blood pressure (BP), depending on the area injected with the agonists. In spite of the association between cardiovascular control and pain modulation, the effects of manipulating NMDAR in pain responses have never been evaluated. In this study, we decreased the expression of NMDAR in the NTS using gene transfer to target receptor subunits and evaluate long-term effects. Seven days after the injection of lentiviral vectors containing the NR1a subunit cDNA of NMDAR, in antisense orientation, into the intermediate NTS of Wistar rats, BP was measured, and the formalin test of nociception was performed. The antisense vector induced a decrease of NR1 expression in the NTS and elicited BP rises and hypoalgesia. Antisense vectors inhibited formalin-evoked c-Fos expression in the spinal cord, indicating decreased nociceptive activity of spinal neurons. Using a time-course approach, we verified that the onset of both the increases in BP and the hypoalgesia was at 4 days after vector injection into the NTS. The injection of NMDA into the NTS reversed the effects of antisense vectors in pain behavioral responses and spinal neuronal activation and decreased BP and heart rate. The present study shows that the NR1 subunit of the NMDAR at the NTS is critical in the regulation of tonic cardiovascular and nociceptive control and shows an involvement of the nucleus in the modulation of sustained pain.
authors.affiliation: Instituto de Farmacologia & Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Marques-Lopes
authors.forename: I
authors.initials: I
authors.lastname: Martins
authors.forename: D
authors.initials: D
authors.lastname: Pinho
authors.forename: M
authors.initials: M
authors.lastname: Morato
authors.forename: S P
authors.initials: SP
authors.lastname: Wilson
authors.forename: A
authors.initials: A
authors.lastname: Albino-Teixeira
authors.forename: I
authors.initials: I
authors.lastname: Tavares
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008392:Marmota; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D017552:Solitary Nucleus / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate