Orexin-2 receptors inhibit primary afferent fiber-evoked responses of ventral roots in the neonatal rat isolated spinal cord.
Orexin-A and orexin-B are hypothalamic peptides. Orexin-A binds equally to both orexin-1 and orexin-2 receptors but orexin-B has a preferential affinity for orexin-2 receptor. In the spinal dorsal horn, orexins have been shown to be concentrated in the superficial laminae. In the present study, the authors examined the effect of spinally applied orexin-A and orexin-B on the primary afferent fiber-evoked nociceptive reflex in the isolated spinal cord of the neonatal rat. In the isolated spinal cord preparation from 0-3day old rats, single-shock stimulation of a dorsal root (L3-L5) at a strength which can activate C-fibers induced a slow depolarizing response lasting about 30s (slow ventral root potential: slow VRP) in the ipsilateral ventral root of the same segment. Bath application of orexin-A and orexin-B inhibited the slow VRP in a concentration-dependent manner. Bath application of SB-334867, a selective orexin-1 receptor antagonist, had no effect on the depressant effect of orexin-A on slow VRP. Bath application of [Ala11,d-Leu15]-orexin B, a selective orexin-2 receptor agonist, depressed the slow VRP. Both orexin-A and orexin-B depressed the level of temporal summation of synaptic activity evoked by 20 repetitive stimulations of the dorsal root. These data suggest that orexin-2 receptor, but not orexin-1 receptor, may play an inhibitory role in nociceptive transmission in the neonatal rat spinal cord.
Department of Anesthesiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Koyo
K
Shono
Tatsuo
T
Yamamoto
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001583:Benzoxazoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D009287:Naphthyridines; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology; D064446:Orexin Receptors; D000068797:Orexins; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D018013:Receptors, Neuropeptide / Q000502:physiology*; D013116:Spinal Cord / Q000033:anatomy & histology*; D013126:Spinal Nerve Roots / Q000378:metabolism*; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D014508:Urea