Metabolite-Sensing Receptors: Emerging Targets for Modulating Chronic Pain Pathways
Chronic pain is a debilitating condition affecting millions worldwide, often resulting from complex interactions between the nervous and immune systems. Recent advances highlight the critical role of metabolite-sensing G protein-coupled receptors (GPCRs) in various chronic pain types. These receptor...
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MDPI AG
2025-01-01
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| Series: | Current Issues in Molecular Biology |
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| author | Ciprian Pușcașu Corina Andrei Octavian Tudorel Olaru Anca Zanfirescu |
| author_facet | Ciprian Pușcașu Corina Andrei Octavian Tudorel Olaru Anca Zanfirescu |
| author_sort | Ciprian Pușcașu |
| collection | DOAJ |
| description | Chronic pain is a debilitating condition affecting millions worldwide, often resulting from complex interactions between the nervous and immune systems. Recent advances highlight the critical role of metabolite-sensing G protein-coupled receptors (GPCRs) in various chronic pain types. These receptors link metabolic changes with cellular responses, influencing inflammatory and degenerative processes. Receptors such as free fatty acid receptor 1 (FFAR1/GPR40), free fatty acid receptor 4 (FFAR4/GPR120), free fatty acid receptor 2 (FFAR2/GPR43), and Takeda G protein-coupled receptor 5 (TGR5/GPR131/GPBAR1) are key modulators of nociceptive signaling. GPR40, activated by long-chain fatty acids, exhibits strong anti-inflammatory effects by reducing cytokine expression. Butyrate-activated GPR43 inhibits inflammatory mediators like nitric oxide synthase-2 and cyclooxygenase-2, mitigating inflammation. TGR5, activated by bile acids, regulates inflammation and cellular senescence through pathways like NF-κB and p38. These receptors are promising therapeutic targets in chronic pain, addressing the metabolic and inflammatory factors underlying nociceptive sensitization and tissue degeneration. This review explores the molecular mechanisms of metabolite-sensing receptors in chronic pain, their therapeutic potential, and challenges in clinical application. By uncovering these mechanisms, metabolite-sensing receptors could lead to safer, more effective pain management strategies. |
| format | Article |
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| institution | Kabale University |
| issn | 1467-3037 1467-3045 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-887cccaa4f0841edbff2f3ddf55c72b02025-01-24T13:27:36ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-01-014716310.3390/cimb47010063Metabolite-Sensing Receptors: Emerging Targets for Modulating Chronic Pain PathwaysCiprian Pușcașu0Corina Andrei1Octavian Tudorel Olaru2Anca Zanfirescu3Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, RomaniaFaculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, RomaniaFaculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, RomaniaFaculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, RomaniaChronic pain is a debilitating condition affecting millions worldwide, often resulting from complex interactions between the nervous and immune systems. Recent advances highlight the critical role of metabolite-sensing G protein-coupled receptors (GPCRs) in various chronic pain types. These receptors link metabolic changes with cellular responses, influencing inflammatory and degenerative processes. Receptors such as free fatty acid receptor 1 (FFAR1/GPR40), free fatty acid receptor 4 (FFAR4/GPR120), free fatty acid receptor 2 (FFAR2/GPR43), and Takeda G protein-coupled receptor 5 (TGR5/GPR131/GPBAR1) are key modulators of nociceptive signaling. GPR40, activated by long-chain fatty acids, exhibits strong anti-inflammatory effects by reducing cytokine expression. Butyrate-activated GPR43 inhibits inflammatory mediators like nitric oxide synthase-2 and cyclooxygenase-2, mitigating inflammation. TGR5, activated by bile acids, regulates inflammation and cellular senescence through pathways like NF-κB and p38. These receptors are promising therapeutic targets in chronic pain, addressing the metabolic and inflammatory factors underlying nociceptive sensitization and tissue degeneration. This review explores the molecular mechanisms of metabolite-sensing receptors in chronic pain, their therapeutic potential, and challenges in clinical application. By uncovering these mechanisms, metabolite-sensing receptors could lead to safer, more effective pain management strategies.https://www.mdpi.com/1467-3045/47/1/63chronic painmetaboliteslong-chain fatty acidsinflammation |
| spellingShingle | Ciprian Pușcașu Corina Andrei Octavian Tudorel Olaru Anca Zanfirescu Metabolite-Sensing Receptors: Emerging Targets for Modulating Chronic Pain Pathways Current Issues in Molecular Biology chronic pain metabolites long-chain fatty acids inflammation |
| title | Metabolite-Sensing Receptors: Emerging Targets for Modulating Chronic Pain Pathways |
| title_full | Metabolite-Sensing Receptors: Emerging Targets for Modulating Chronic Pain Pathways |
| title_fullStr | Metabolite-Sensing Receptors: Emerging Targets for Modulating Chronic Pain Pathways |
| title_full_unstemmed | Metabolite-Sensing Receptors: Emerging Targets for Modulating Chronic Pain Pathways |
| title_short | Metabolite-Sensing Receptors: Emerging Targets for Modulating Chronic Pain Pathways |
| title_sort | metabolite sensing receptors emerging targets for modulating chronic pain pathways |
| topic | chronic pain metabolites long-chain fatty acids inflammation |
| url | https://www.mdpi.com/1467-3045/47/1/63 |
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