Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats

Levodopa possesses antinociceptive actions against several somatic pain conditions. However, we do not know at this moment whether levodopa is also effective to visceral pain. The present study was therefore performed to clarify whether levodopa is effective to visceral pain and its mechanisms. Visc...

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Main Authors: Toshikatsu Okumura, Tsukasa Nozu, Shima Kumei, Kaoru Takakusaki, Saori Miyagishi, Masumi Ohhira
Format: Article
Language:English
Published: Elsevier 2016-02-01
Series:Journal of Pharmacological Sciences
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861316000086
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author Toshikatsu Okumura
Tsukasa Nozu
Shima Kumei
Kaoru Takakusaki
Saori Miyagishi
Masumi Ohhira
author_facet Toshikatsu Okumura
Tsukasa Nozu
Shima Kumei
Kaoru Takakusaki
Saori Miyagishi
Masumi Ohhira
author_sort Toshikatsu Okumura
collection DOAJ
description Levodopa possesses antinociceptive actions against several somatic pain conditions. However, we do not know at this moment whether levodopa is also effective to visceral pain. The present study was therefore performed to clarify whether levodopa is effective to visceral pain and its mechanisms. Visceral sensation was evaluated by colonic distension-induced abdominal withdrawal reflex (AWR) in conscious rats. Subcutaneously (80 mg/rat) or intracisternally (2.5 μg/rat) administered levodopa significantly increased the threshold of colonic distension-induced AWR in conscious rats. The dose difference to induce the antinociceptive action suggests levodopa acts centrally to exert its antinociceptive action against colonic distension. While neither sulpiride, a D2 dopamine receptor antagonist, nor SCH23390, a D1 dopamine receptor antagonist by itself changed the threshold of colonic distension-induced AWR, the intracisternally injected levodopa-induced antinociceptive action was significantly blocked by pretreatment with subcutaneously administered sulpiride but not SCH23390. Treatment with intracisternal SB334867, an orexin 1 receptor antagonist, significantly blocked the subcutaneously administered levodopa-induced antinociceptive action. These results suggest that levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain.
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spelling doaj.art-3263716bf5c245c8aa9749ff82068f722022-12-22T00:32:52ZengElsevierJournal of Pharmacological Sciences1347-86132016-02-01130212312710.1016/j.jphs.2016.01.007Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious ratsToshikatsu Okumura0Tsukasa Nozu1Shima Kumei2Kaoru Takakusaki3Saori Miyagishi4Masumi Ohhira5Department of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, JapanDepartment of Regional Medicine and Education, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, JapanDepartment of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, JapanResearch Center for Brain Function and Medical Engineering, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, JapanDepartment of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, JapanDepartment of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, JapanLevodopa possesses antinociceptive actions against several somatic pain conditions. However, we do not know at this moment whether levodopa is also effective to visceral pain. The present study was therefore performed to clarify whether levodopa is effective to visceral pain and its mechanisms. Visceral sensation was evaluated by colonic distension-induced abdominal withdrawal reflex (AWR) in conscious rats. Subcutaneously (80 mg/rat) or intracisternally (2.5 μg/rat) administered levodopa significantly increased the threshold of colonic distension-induced AWR in conscious rats. The dose difference to induce the antinociceptive action suggests levodopa acts centrally to exert its antinociceptive action against colonic distension. While neither sulpiride, a D2 dopamine receptor antagonist, nor SCH23390, a D1 dopamine receptor antagonist by itself changed the threshold of colonic distension-induced AWR, the intracisternally injected levodopa-induced antinociceptive action was significantly blocked by pretreatment with subcutaneously administered sulpiride but not SCH23390. Treatment with intracisternal SB334867, an orexin 1 receptor antagonist, significantly blocked the subcutaneously administered levodopa-induced antinociceptive action. These results suggest that levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain.http://www.sciencedirect.com/science/article/pii/S1347861316000086LevodopaDopamineOrexinAntinociceptionColonic distension
spellingShingle Toshikatsu Okumura
Tsukasa Nozu
Shima Kumei
Kaoru Takakusaki
Saori Miyagishi
Masumi Ohhira
Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats
Journal of Pharmacological Sciences
Levodopa
Dopamine
Orexin
Antinociception
Colonic distension
title Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats
title_full Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats
title_fullStr Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats
title_full_unstemmed Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats
title_short Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats
title_sort levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of d2 dopamine receptors and the orexinergic system in the brain in conscious rats
topic Levodopa
Dopamine
Orexin
Antinociception
Colonic distension
url http://www.sciencedirect.com/science/article/pii/S1347861316000086
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