OX2 receptors mediate the inhibitory effects of orexin‐A on potassium chloride‐induced increases in intracellular calcium ion levels in neurons derived from rat dorsal root ganglion in a chronic pain model
Abstract Aims Orexin‐A is known to induce anti‐nociceptive effects in animal models of chronic pain. We have found that orexin‐A inhibits KCl loading‐induced increases in the intracellular calcium ion levels ([Ca2+]i) in C‐fiber‐like neurons of rats showing inflammatory nociceptive behavior. Here, w...
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| Format: | Article |
| Language: | English |
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Wiley
2020-03-01
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| Series: | Neuropsychopharmacology Reports |
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| Online Access: | https://doi.org/10.1002/npr2.12094 |
| _version_ | 1811185608514600960 |
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| author | Masami Yamaguchi Manabu Ishikawa Yuri Aono Tadashi Saigusa |
| author_facet | Masami Yamaguchi Manabu Ishikawa Yuri Aono Tadashi Saigusa |
| author_sort | Masami Yamaguchi |
| collection | DOAJ |
| description | Abstract Aims Orexin‐A is known to induce anti‐nociceptive effects in animal models of chronic pain. We have found that orexin‐A inhibits KCl loading‐induced increases in the intracellular calcium ion levels ([Ca2+]i) in C‐fiber‐like neurons of rats showing inflammatory nociceptive behavior. Here, we examined the effects of orexin‐A on the depolarization of C‐fiber‐like neurons derived from a rat model for another type of chronic pain, namely neuropathic pain. Thus, we analyzed the effects of orexin‐A on KCl‐induced increases in [Ca2+]i in C‐fiber‐like neurons of rats with sciatic nerve ligation. Methods Paw withdrawal and threshold force in response to tactile stimuli were evaluated using von Frey filaments. Sham‐operated rats served as controls. [Ca2+]i in neurons were visualized by calcium fluorescent probe. Changes in [Ca2+]i were assessed using relative fluorescence intensity. Results Seven days after sciatic nerve ligation, paw withdrawal and threshold force for tactile stimuli were increased and reduced, respectively. KCl loading to neurons from either sciatic nerve‐ligated or control rats increased relative fluorescence intensity. The KCl‐induced increase in relative fluorescence intensity in sciatic nerve‐ligated, but not that of control, rats was inhibited by orexin‐A. The OX1 and OX2 receptor antagonist MK‐4305 and OX2 receptor antagonist EMPA, but not the OX1 receptor antagonist SB 334867, each counteracted orexin‐A‐induced inhibition of KCl‐provoked increases in relative fluorescence intensity. Conclusion The present findings constitute neuropharmacological evidence that OX2 but not OX1 receptors mediate the inhibitory effects of orexin‐A on KCl‐induced increases in [Ca2+]i in C‐fiber‐like neurons of rats showing hyperalgesia provoked by sciatic nerve ligation. |
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| institution | Directory Open Access Journal |
| issn | 2574-173X |
| language | English |
| last_indexed | 2024-04-11T13:33:13Z |
| publishDate | 2020-03-01 |
| publisher | Wiley |
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| series | Neuropsychopharmacology Reports |
| spelling | doaj.art-5c7128a7a5d747e4adfb6610db139eb92022-12-22T04:21:43ZengWileyNeuropsychopharmacology Reports2574-173X2020-03-01401303810.1002/npr2.12094OX2 receptors mediate the inhibitory effects of orexin‐A on potassium chloride‐induced increases in intracellular calcium ion levels in neurons derived from rat dorsal root ganglion in a chronic pain modelMasami Yamaguchi0Manabu Ishikawa1Yuri Aono2Tadashi Saigusa3Department of Anesthesiology Nihon University School of Dentistry at Matsudo Matsudo JapanDepartment of Anesthesiology Nihon University School of Dentistry at Matsudo Matsudo JapanDepartment of Pharmacology Nihon University School of Dentistry at Matsudo Matsudo JapanDepartment of Pharmacology Nihon University School of Dentistry at Matsudo Matsudo JapanAbstract Aims Orexin‐A is known to induce anti‐nociceptive effects in animal models of chronic pain. We have found that orexin‐A inhibits KCl loading‐induced increases in the intracellular calcium ion levels ([Ca2+]i) in C‐fiber‐like neurons of rats showing inflammatory nociceptive behavior. Here, we examined the effects of orexin‐A on the depolarization of C‐fiber‐like neurons derived from a rat model for another type of chronic pain, namely neuropathic pain. Thus, we analyzed the effects of orexin‐A on KCl‐induced increases in [Ca2+]i in C‐fiber‐like neurons of rats with sciatic nerve ligation. Methods Paw withdrawal and threshold force in response to tactile stimuli were evaluated using von Frey filaments. Sham‐operated rats served as controls. [Ca2+]i in neurons were visualized by calcium fluorescent probe. Changes in [Ca2+]i were assessed using relative fluorescence intensity. Results Seven days after sciatic nerve ligation, paw withdrawal and threshold force for tactile stimuli were increased and reduced, respectively. KCl loading to neurons from either sciatic nerve‐ligated or control rats increased relative fluorescence intensity. The KCl‐induced increase in relative fluorescence intensity in sciatic nerve‐ligated, but not that of control, rats was inhibited by orexin‐A. The OX1 and OX2 receptor antagonist MK‐4305 and OX2 receptor antagonist EMPA, but not the OX1 receptor antagonist SB 334867, each counteracted orexin‐A‐induced inhibition of KCl‐provoked increases in relative fluorescence intensity. Conclusion The present findings constitute neuropharmacological evidence that OX2 but not OX1 receptors mediate the inhibitory effects of orexin‐A on KCl‐induced increases in [Ca2+]i in C‐fiber‐like neurons of rats showing hyperalgesia provoked by sciatic nerve ligation.https://doi.org/10.1002/npr2.12094chronic painintracellular calcium ion levelsorexin receptororexin‐Arat |
| spellingShingle | Masami Yamaguchi Manabu Ishikawa Yuri Aono Tadashi Saigusa OX2 receptors mediate the inhibitory effects of orexin‐A on potassium chloride‐induced increases in intracellular calcium ion levels in neurons derived from rat dorsal root ganglion in a chronic pain model Neuropsychopharmacology Reports chronic pain intracellular calcium ion levels orexin receptor orexin‐A rat |
| title | OX2 receptors mediate the inhibitory effects of orexin‐A on potassium chloride‐induced increases in intracellular calcium ion levels in neurons derived from rat dorsal root ganglion in a chronic pain model |
| title_full | OX2 receptors mediate the inhibitory effects of orexin‐A on potassium chloride‐induced increases in intracellular calcium ion levels in neurons derived from rat dorsal root ganglion in a chronic pain model |
| title_fullStr | OX2 receptors mediate the inhibitory effects of orexin‐A on potassium chloride‐induced increases in intracellular calcium ion levels in neurons derived from rat dorsal root ganglion in a chronic pain model |
| title_full_unstemmed | OX2 receptors mediate the inhibitory effects of orexin‐A on potassium chloride‐induced increases in intracellular calcium ion levels in neurons derived from rat dorsal root ganglion in a chronic pain model |
| title_short | OX2 receptors mediate the inhibitory effects of orexin‐A on potassium chloride‐induced increases in intracellular calcium ion levels in neurons derived from rat dorsal root ganglion in a chronic pain model |
| title_sort | ox2 receptors mediate the inhibitory effects of orexin a on potassium chloride induced increases in intracellular calcium ion levels in neurons derived from rat dorsal root ganglion in a chronic pain model |
| topic | chronic pain intracellular calcium ion levels orexin receptor orexin‐A rat |
| url | https://doi.org/10.1002/npr2.12094 |
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