title: The role of trigeminal nucleus caudalis orexin 1 receptors in orofacial pain transmission and in orofacial pain-induced learning and memory impairment in rats.
abstract: It is widely accepted that the spinal trigeminal nuclear complex, especially the subnucleus caudalis (Vc), receives input from orofacial structures. The neuropeptides orexin-A and -B are expressed in multiple neuronal systems. Orexin signaling has been implicated in pain-modulating system as well as learning and memory processes. Orexin 1 receptor (OX1R) has been reported in trigeminal nucleus caudalis. However, its roles in trigeminal pain modulation have not been elucidated so far. This study was designed to investigate the role of Vc OX1R in the modulation of orofacial pain as well as pain-induced learning and memory deficits. Orofacial pain was induced by subcutaneous injection of capsaicin in the right upper lip of the rats. OX1R agonist (orexin-A) and antagonist (SB-334867-A) were microinjected into Vc prior capsaicin administration. After recording nociceptive times, learning and memory was investigated using Morris water maze (MWM) test. The results indicated that, orexin-A (150 pM/rat) significantly reduced the nociceptive times, while SB334867-A (80 nM/rat) exaggerated nociceptive behavior in response to capsaicin injection. In MWM test, capsaicin-treated rats showed a significant learning and memory impairment. Moreover, SB-334867-A (80 nM/rat) significantly exaggerated learning and memory impairment in capsaicin-treated rats. However, administration of orexin-A (100 pM/rat) prevented learning and memory deficits. Taken together, these results indicate that Vc OX1R was at least in part involved in orofacial pain transmission and orexin-A has also a beneficial inhibitory effect on orofacial pain-induced deficits in abilities of spatial learning and memory.
authors.affiliation: Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran. Electronic address: kooshki.razieh@gmail.com.
authors.forename: Razieh
authors.initials: R
authors.lastname: Kooshki
authors.affiliation: Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran. Electronic address: mabbas@uk.ac.ir.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Abbasnejad
authors.affiliation: Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran. Electronic address: Semahani@yahoo.com.
authors.forename: Saeed
authors.initials: S
authors.lastname: Esmaeili-Mahani
authors.affiliation: Laboratory of Molecular Neuroscience, Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; Endodontology Research Center, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: Maryam.raoof@gmail.com.
authors.forename: Maryam
authors.initials: M
authors.lastname: Raoof
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005157:Facial Pain / Q000150:complications* / Q000473:pathology*; D007859:Learning Disabilities / Q000209:etiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology*; D009043:Motor Activity / Q000187:drug effects; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology; D064446:Orexin Receptors / Q000819:agonists / Q000378:metabolism*; D000068797:Orexins / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D018689:Sensory System Agents / Q000494:pharmacology; D065853:Spatial Learning / Q000187:drug effects; D014278:Trigeminal Nuclei / Q000378:metabolism*; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D018689:Sensory System Agents; D014508:Urea; D002211:Capsaicin
keywords: Learning and memory; Orexin-A; Orofacial pain; SB-334867-A; Trigeminal nucleus caudalis