Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons
Abstract There is increasing evidence of sex differences in underlying mechanisms causing pain in preclinical models, and in clinical populations. There are also important disconnects between clinical pain populations and the way preclinical pain studies are conducted. For instance, osteoarthritis p...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-31603-x |
| _version_ | 1827979497138290688 |
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| author | Breanna Q. Shen Ishwarya Sankaranarayanan Theodore J. Price Diana Tavares-Ferreira |
| author_facet | Breanna Q. Shen Ishwarya Sankaranarayanan Theodore J. Price Diana Tavares-Ferreira |
| author_sort | Breanna Q. Shen |
| collection | DOAJ |
| description | Abstract There is increasing evidence of sex differences in underlying mechanisms causing pain in preclinical models, and in clinical populations. There are also important disconnects between clinical pain populations and the way preclinical pain studies are conducted. For instance, osteoarthritis pain more frequently affects women, but most preclinical studies have been conducted using males in animal models. The most widely used painkillers, nonsteroidal anti-inflammatory drugs (NSAIDs), act on the prostaglandin pathway by inhibiting cyclooxygenase (COX) enzymes. The purpose of this study was to analyze the preclinical and clinical literature on the role of prostaglandins and COX in inflammation and pain. We aimed to specifically identify studies that used both sexes and investigate whether any sex-differences in the action of prostaglandins and COX inhibition had been reported, either in clinical or preclinical studies. We conducted a PubMed search and identified 369 preclinical studies and 100 clinical studies that matched our inclusion/exclusion criteria. Our analysis shows that only 17% of preclinical studies on prostaglandins used both sexes and, out of those, only 19% analyzed or reported data separated by sex. In contrast, 79% of the clinical studies analyzed used both sexes. However, only 6% of those reported data separated by sex. Interestingly, 14 out of 15 preclinical studies and 5 out of 6 clinical studies that analyzed data separated by sex have identified sex-differences. This builds on the increasing evidence of sex-differences in prostaglandin signaling and the importance of sex as a biological variable in data analysis. The preclinical literature identifies a sex difference in prostaglandin D2 synthase (PTGDS) expression where it is higher in female than in male rodents in the nervous system. We experimentally validated that PTGDS expression is higher in female human dorsal root ganglia (DRG) neurons recovered from organ donors. Our semi-systematic literature review reveals a need for continued inclusivity of both male and female animals in prostaglandins studies and data analysis separated by sex in preclinical and clinical studies. Our finding of sex-differences in neuronal PTGDS expression in humans exemplifies the need for a more comprehensive understanding of how the prostaglandin system functions in the DRG in rodents and humans. |
| first_indexed | 2024-04-09T21:37:40Z |
| format | Article |
| id | doaj.art-2b9418a95a254a86aa00772dab70eca6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T21:37:40Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2b9418a95a254a86aa00772dab70eca62023-03-26T11:10:38ZengNature PortfolioScientific Reports2045-23222023-03-0113111310.1038/s41598-023-31603-xSex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neuronsBreanna Q. Shen0Ishwarya Sankaranarayanan1Theodore J. Price2Diana Tavares-Ferreira3Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at DallasDepartment of Neuroscience and Center for Advanced Pain Studies, University of Texas at DallasDepartment of Neuroscience and Center for Advanced Pain Studies, University of Texas at DallasDepartment of Neuroscience and Center for Advanced Pain Studies, University of Texas at DallasAbstract There is increasing evidence of sex differences in underlying mechanisms causing pain in preclinical models, and in clinical populations. There are also important disconnects between clinical pain populations and the way preclinical pain studies are conducted. For instance, osteoarthritis pain more frequently affects women, but most preclinical studies have been conducted using males in animal models. The most widely used painkillers, nonsteroidal anti-inflammatory drugs (NSAIDs), act on the prostaglandin pathway by inhibiting cyclooxygenase (COX) enzymes. The purpose of this study was to analyze the preclinical and clinical literature on the role of prostaglandins and COX in inflammation and pain. We aimed to specifically identify studies that used both sexes and investigate whether any sex-differences in the action of prostaglandins and COX inhibition had been reported, either in clinical or preclinical studies. We conducted a PubMed search and identified 369 preclinical studies and 100 clinical studies that matched our inclusion/exclusion criteria. Our analysis shows that only 17% of preclinical studies on prostaglandins used both sexes and, out of those, only 19% analyzed or reported data separated by sex. In contrast, 79% of the clinical studies analyzed used both sexes. However, only 6% of those reported data separated by sex. Interestingly, 14 out of 15 preclinical studies and 5 out of 6 clinical studies that analyzed data separated by sex have identified sex-differences. This builds on the increasing evidence of sex-differences in prostaglandin signaling and the importance of sex as a biological variable in data analysis. The preclinical literature identifies a sex difference in prostaglandin D2 synthase (PTGDS) expression where it is higher in female than in male rodents in the nervous system. We experimentally validated that PTGDS expression is higher in female human dorsal root ganglia (DRG) neurons recovered from organ donors. Our semi-systematic literature review reveals a need for continued inclusivity of both male and female animals in prostaglandins studies and data analysis separated by sex in preclinical and clinical studies. Our finding of sex-differences in neuronal PTGDS expression in humans exemplifies the need for a more comprehensive understanding of how the prostaglandin system functions in the DRG in rodents and humans.https://doi.org/10.1038/s41598-023-31603-x |
| spellingShingle | Breanna Q. Shen Ishwarya Sankaranarayanan Theodore J. Price Diana Tavares-Ferreira Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons Scientific Reports |
| title | Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons |
| title_full | Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons |
| title_fullStr | Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons |
| title_full_unstemmed | Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons |
| title_short | Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons |
| title_sort | sex differences in prostaglandin signaling a semi systematic review and characterization of ptgds expression in human sensory neurons |
| url | https://doi.org/10.1038/s41598-023-31603-x |
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