The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management
Over the past decades, accumulating evidence has demonstrated a pivotal role of cholecystokinin type 2 receptor (CCK2R) in pain modulation. The established role of CCK2R activation in directly facilitating nociception has led to the development of several CCK2R antagonists, which have been shown to...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/11/1185 |
| _version_ | 1797508834581807104 |
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| author | Amandine Bernard Aurore Danigo Sylvie Bourthoumieu Mohamad Mroué Alexis Desmoulière Franck Sturtz Amandine Rovini Claire Demiot |
| author_facet | Amandine Bernard Aurore Danigo Sylvie Bourthoumieu Mohamad Mroué Alexis Desmoulière Franck Sturtz Amandine Rovini Claire Demiot |
| author_sort | Amandine Bernard |
| collection | DOAJ |
| description | Over the past decades, accumulating evidence has demonstrated a pivotal role of cholecystokinin type 2 receptor (CCK2R) in pain modulation. The established role of CCK2R activation in directly facilitating nociception has led to the development of several CCK2R antagonists, which have been shown to successfully alleviate pain in several rodent models of pain. However, the outcomes of clinical trials are more modest since they have not demonstrated the expected biological effect obtained in animals. Such discordances of results between preclinical and clinical studies suggest reconsidering our knowledge about the molecular basis of the pharmacology and functioning of CCK2R. This review focuses on the cellular localization of CCK2R specifically in the sensory nervous system and discusses in further detail the molecular mechanisms and signal transduction pathways involved in controlling pain perception. We then provide a comprehensive overview of the most successful compounds targeting CCK2R and report recent advances in pharmacological strategies used to achieve CCK2R modulation. We purposely distinguish between CCK2R benefits obtained in preclinical models and outcomes in clinical trials with different pain etiologies. Lastly, we emphasize the biological and clinical relevance of CCK2R as a promising target for the development of new treatments for pain management. |
| first_indexed | 2024-03-10T05:10:29Z |
| format | Article |
| id | doaj.art-f33ce5bb1927427ab60341e936ffe901 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T05:10:29Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-f33ce5bb1927427ab60341e936ffe9012023-11-23T00:56:33ZengMDPI AGPharmaceuticals1424-82472021-11-011411118510.3390/ph14111185The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain ManagementAmandine Bernard0Aurore Danigo1Sylvie Bourthoumieu2Mohamad Mroué3Alexis Desmoulière4Franck Sturtz5Amandine Rovini6Claire Demiot7EA6309—MMNP, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceEA6309—MMNP, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceEA6309—MMNP, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceEA6309—MMNP, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceEA6309—MMNP, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceEA6309—MMNP, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceEA6309—MMNP, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceEA6309—MMNP, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceOver the past decades, accumulating evidence has demonstrated a pivotal role of cholecystokinin type 2 receptor (CCK2R) in pain modulation. The established role of CCK2R activation in directly facilitating nociception has led to the development of several CCK2R antagonists, which have been shown to successfully alleviate pain in several rodent models of pain. However, the outcomes of clinical trials are more modest since they have not demonstrated the expected biological effect obtained in animals. Such discordances of results between preclinical and clinical studies suggest reconsidering our knowledge about the molecular basis of the pharmacology and functioning of CCK2R. This review focuses on the cellular localization of CCK2R specifically in the sensory nervous system and discusses in further detail the molecular mechanisms and signal transduction pathways involved in controlling pain perception. We then provide a comprehensive overview of the most successful compounds targeting CCK2R and report recent advances in pharmacological strategies used to achieve CCK2R modulation. We purposely distinguish between CCK2R benefits obtained in preclinical models and outcomes in clinical trials with different pain etiologies. Lastly, we emphasize the biological and clinical relevance of CCK2R as a promising target for the development of new treatments for pain management.https://www.mdpi.com/1424-8247/14/11/1185cholecystokinin type 2 receptorpain managementantagonistrodent modelclinical trial |
| spellingShingle | Amandine Bernard Aurore Danigo Sylvie Bourthoumieu Mohamad Mroué Alexis Desmoulière Franck Sturtz Amandine Rovini Claire Demiot The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management Pharmaceuticals cholecystokinin type 2 receptor pain management antagonist rodent model clinical trial |
| title | The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management |
| title_full | The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management |
| title_fullStr | The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management |
| title_full_unstemmed | The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management |
| title_short | The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management |
| title_sort | cholecystokinin type 2 receptor a pharmacological target for pain management |
| topic | cholecystokinin type 2 receptor pain management antagonist rodent model clinical trial |
| url | https://www.mdpi.com/1424-8247/14/11/1185 |
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