Spinal nociceptin inhibits AMPA-induced nociceptive behavior and Fos expression in rat spinal cord.
The effects of intrathecal nociceptin (NOCI) on the nociceptive behavior (biting, scratching and licking; BSL) and the spinal Fos expression induced by intrathecal administration of N-methyl-D-aspartate (NMDA, 4 microg/rat) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, 2 microg/rat) were studied. Coadministration of NOCI (3 and 10 nmol/rat) with NMDA did not modify the NMDA-induced BSL or Fos expression. In contrast, NOCI (0.1-3 nmol/rat) dose-dependently inhibited the BSL behavior induced by AMPA. Furthermore, coadministration of NOCI (3 and 10 nmol/rat) significantly reduced the AMPA-induced expression of Fos protein in the superficial layers of the spinal dorsal horn. In order to test whether classical or opioid receptor-like type 1 (ORL1) receptors are involved in the inhibitions by NOCI of AMPA-evoked BSL, the corresponding antagonists were assayed. The administration of the nonselective opioid receptor antagonist, naloxone (10 mg/kg i.p.), did not modify the NOCI-induced inhibition of AMPA-evoked BSL. However, the selective ORL1 receptor antagonist, [N-Phe(1)]nociceptin-(1-13)-NH(2) (90 nmol/rat i.t.), completely prevented the NOCI-mediated inhibition of the nociceptive responses evoked by AMPA. In conclusion, NOCI, acting at ORL1 receptors can, at least in part, induce spinal analgesia by blocking the nociceptive responses produced through the stimulation of AMPA receptors.
Menéndez
Luis
L
Laboratorio de Farmacologi;a, Facultad de Medicina, Instituto Universitario de Oncologi;a del Principado de Asturias (IUOPA), Universidad de Oviedo, C/ Julián Clavería 6, 33006, Asturias, Oviedo, Spain. luismen@correo.uniovi.es
Lastra
Ana
A
Villanueva
Noemí
N
Hidalgo
Agustín
A
Baamonde
Ana
A
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018847:Opioid Peptides / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000097629:Nociceptin
D018847:Opioid Peptides; D016760:Proto-Oncogene Proteins c-fos; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000097629:Nociceptin