NMDA receptor antagonists attenuate intrathecal morphine-induced pruritus through ERK phosphorylation
Abstract Pruritus is the most common complication of intrathecal morphine; however, its exact molecular mechanism is unclear, and treatment is challenging. The analgesic effect of N-methyl-D-aspartate (NMDA) receptor antagonists and the morphine-associated increase in NMDA receptor activation sugges...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-06-01
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| Series: | Molecular Brain |
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| Online Access: | http://link.springer.com/article/10.1186/s13041-018-0379-2 |
| _version_ | 1818621783446650880 |
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| author | Le Shen Weijia Wang Siyu Li Jing Qin Yuguang Huang |
| author_facet | Le Shen Weijia Wang Siyu Li Jing Qin Yuguang Huang |
| author_sort | Le Shen |
| collection | DOAJ |
| description | Abstract Pruritus is the most common complication of intrathecal morphine; however, its exact molecular mechanism is unclear, and treatment is challenging. The analgesic effect of N-methyl-D-aspartate (NMDA) receptor antagonists and the morphine-associated increase in NMDA receptor activation suggest potential role of NMDA receptor in the spinal itch sensation. Male C57BL/6 mice were given intrathecal morphine to induce scratching behavior. The effects of NMDA, ketamine, ifenprodil and U0126 on morphine-induced pruritus and analgesia were evaluated also. The number of scratching responses was counted for 30 min post-injection to evaluate pruritus. A warm-water tail immersion assay was conducted before and until 120 min post-injection at 30-min intervals. Percent of maximal possible effect (%MPE) and area under curve (AUC) were calculated based on tail-flick latency to evaluate analgesic efficacy. Compared with control treatment, intrathecal morphine elicited an obvious scratching response and analgesic effect in a dose dependent manner. Ketamine (1 μg), ifenprodil (0.1 μg) and U0126 (0.1 μg and 1.0 μg) all significantly attenuated morphine induced scratches. Ifenprodil (0.1 μg) injection significantly prolonged the analgesic effect of intrathecal morphine. The ERK1/2 phosphorylation induced by intrathecal morphine was inhibited by ketamine, ifenprodil and U0126 as well. U0126 inhibited morphine-induced pruritus with no effect on its analgesia. Therefore, intrathecal coadministration of morphine with NMDA receptor antagonists ketamine and ifenprodil alleviated morphine-induced scratching. Intrathecal morphine increased ERK phosphorylation in the lumbar spinal dorsal horn, which may be related with morphine-induced pruritus, and was counteracted by NMDA receptor antagonists. |
| first_indexed | 2024-12-16T18:14:46Z |
| format | Article |
| id | doaj.art-432876bd00014baa90f9e68b1d5027b7 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-16T18:14:46Z |
| publishDate | 2018-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-432876bd00014baa90f9e68b1d5027b72022-12-21T22:21:40ZengBMCMolecular Brain1756-66062018-06-0111111010.1186/s13041-018-0379-2NMDA receptor antagonists attenuate intrathecal morphine-induced pruritus through ERK phosphorylationLe Shen0Weijia Wang1Siyu Li2Jing Qin3Yuguang Huang4Department of Anesthesiology, Peking Union Medical College HospitalDepartment of Anesthesiology, Peking Union Medical College HospitalDepartment of Anesthesiology, Peking Union Medical College HospitalDepartment of Anesthesiology, Peking Union Medical College HospitalDepartment of Anesthesiology, Peking Union Medical College HospitalAbstract Pruritus is the most common complication of intrathecal morphine; however, its exact molecular mechanism is unclear, and treatment is challenging. The analgesic effect of N-methyl-D-aspartate (NMDA) receptor antagonists and the morphine-associated increase in NMDA receptor activation suggest potential role of NMDA receptor in the spinal itch sensation. Male C57BL/6 mice were given intrathecal morphine to induce scratching behavior. The effects of NMDA, ketamine, ifenprodil and U0126 on morphine-induced pruritus and analgesia were evaluated also. The number of scratching responses was counted for 30 min post-injection to evaluate pruritus. A warm-water tail immersion assay was conducted before and until 120 min post-injection at 30-min intervals. Percent of maximal possible effect (%MPE) and area under curve (AUC) were calculated based on tail-flick latency to evaluate analgesic efficacy. Compared with control treatment, intrathecal morphine elicited an obvious scratching response and analgesic effect in a dose dependent manner. Ketamine (1 μg), ifenprodil (0.1 μg) and U0126 (0.1 μg and 1.0 μg) all significantly attenuated morphine induced scratches. Ifenprodil (0.1 μg) injection significantly prolonged the analgesic effect of intrathecal morphine. The ERK1/2 phosphorylation induced by intrathecal morphine was inhibited by ketamine, ifenprodil and U0126 as well. U0126 inhibited morphine-induced pruritus with no effect on its analgesia. Therefore, intrathecal coadministration of morphine with NMDA receptor antagonists ketamine and ifenprodil alleviated morphine-induced scratching. Intrathecal morphine increased ERK phosphorylation in the lumbar spinal dorsal horn, which may be related with morphine-induced pruritus, and was counteracted by NMDA receptor antagonists.http://link.springer.com/article/10.1186/s13041-018-0379-2Intrathecal morphinepruritusanalgesiaNMDA receptor antagonistERK |
| spellingShingle | Le Shen Weijia Wang Siyu Li Jing Qin Yuguang Huang NMDA receptor antagonists attenuate intrathecal morphine-induced pruritus through ERK phosphorylation Molecular Brain Intrathecal morphine pruritus analgesia NMDA receptor antagonist ERK |
| title | NMDA receptor antagonists attenuate intrathecal morphine-induced pruritus through ERK phosphorylation |
| title_full | NMDA receptor antagonists attenuate intrathecal morphine-induced pruritus through ERK phosphorylation |
| title_fullStr | NMDA receptor antagonists attenuate intrathecal morphine-induced pruritus through ERK phosphorylation |
| title_full_unstemmed | NMDA receptor antagonists attenuate intrathecal morphine-induced pruritus through ERK phosphorylation |
| title_short | NMDA receptor antagonists attenuate intrathecal morphine-induced pruritus through ERK phosphorylation |
| title_sort | nmda receptor antagonists attenuate intrathecal morphine induced pruritus through erk phosphorylation |
| topic | Intrathecal morphine pruritus analgesia NMDA receptor antagonist ERK |
| url | http://link.springer.com/article/10.1186/s13041-018-0379-2 |
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