title: Orexin-A modulates excitatory synaptic transmission and neuronal excitability in the spinal cord substantia gelatinosa.
abstract: Although intrathecal orexin-A has been known to be antinociceptive in various pain models, the role of orexin-A in antinociception is not well characterized. In the present study, we examined whether orexin-A modulates primary afferent fiber-mediated or spontaneous excitatory synaptic transmission using transverse spinal cord slices with attached dorsal root. Bath-application of orexin-A (100nM) reduced the amplitude of excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation of Aδ- or C-primary afferent fibers. The magnitude of reduction was much larger for EPSCs evoked by polysynaptic C-fibers than polysynaptic Aδ-fibers, whereas it was similar in EPSCs evoked by monosynaptic Aδ- or C-fibers. SB674042, an orexin-1 receptor antagonist, but not EMPA, an orexin-2 receptor antagonist, significantly inhibited the orexin-A-induced reduction in EPSC amplitude from mono- or polysynaptic Aδ-fibers, as well as from mono- or polysynaptic C-fibers. Furthermore, orexin-A significantly increased the frequency of spontaneous EPSCs but not the amplitude. This increase was almost completely blocked by both SB674042 and EMPA. On the other hand, orexin-A produced membrane oscillations and inward currents in the SG neurons that were partially or completely inhibited by SB674042 or EMPA, respectively. Thus, this study suggests that the spinal actions of orexin-A underlie orexin-A-induced antinociceptive effects via different subtypes of orexin receptors.
authors.affiliation: Department of Anesthesiology and Pain Medicine, School of Dentistry, Kyungpook National University, Daegu 700-706, Republic of Korea.
authors.forename: Younghoon
authors.initials: Y
authors.lastname: Jeon
authors.affiliation: Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Daegu 700-721, Republic of Korea. Electronic address: pakkibum@naver.com.
authors.forename: Ki Bum
authors.initials: KB
authors.lastname: Park
authors.affiliation: Department of Physiology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Rokeya
authors.initials: R
authors.lastname: Pervin
authors.affiliation: Department of Physiology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Tae Wan
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 700-706, Republic of Korea. Electronic address: dyoun@knu.ac.kr.
authors.forename: Dong-ho
authors.initials: DH
authors.lastname: Youn
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D059225:Nociception; D064446:Orexin Receptors / Q000502:physiology; D000068797:Orexins / Q000378:metabolism* / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013376:Substantia Gelatinosa / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D064446:Orexin Receptors; D000068797:Orexins
keywords: Excitatory synaptic transmission; Orexin receptor; Orexin-A; Oscillation; Spinal substantia gelatinosa