Association of the resolvin precursor 17-HDHA, but not D-or E-series resolvins, with heat pain sensitivity and osteoarthritis pain in humans

Ana M. Valdes; Srinivasarao Ravipati; Cristina Menni; Abhishek Abhishek; Sarah Metrustry; Juliette Harris; Ayrun Nessa; Frances M.K. Williams; Tim D. Spector; Michael Doherty; Victoria Chapman; David A. Barrett

doi:10.1038/s41598-017-09516-3

Association of the resolvin precursor 17-HDHA, but not D-or E-series resolvins, with heat pain sensitivity and osteoarthritis pain in humans

Ana M. Valdes^*, Srinivasarao Ravipati, Cristina Menni, Abhishek Abhishek, Sarah Metrustry, Juliette Harris, Ayrun Nessa, Frances M.K. Williams, Tim D. Spector, Michael Doherty, Victoria Chapman, David A. Barrett

^*Corresponding author for this work

Twin Research & Genetic Epidemiology

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Abstract

Resolvins are omega-3 fatty acid derived potent bioactive lipids that resolve inflammation and modulate transient receptor potential channels. Exogenous administration of the resolvin precursor 17-HDHA shows a strong analgesic effect in animal models of osteoarthritis and acute inflammatory pain, but has not been studied in humans. Our aim was to assess the role of 17-HDHA and resolvins in heat pain sensitivity and in osteoarthritis pain in humans. Resolvins D1, D2, D3, D5, E1 and 17-HDHA, were measured by liquid chromatography-mass spectrometry and tested for association with heat pain thresholds in 250 healthy volunteers who had undergone quantitative sensory testing. Resolvins D1, D2 and 17-HDHA were then tested in 62 individuals affected with knee osteoarthritis and 52 age matched controls and tested for association with knee pain. Circulating levels of docosahexaenoic acid (DHA) were also measured. Levels of 17-HDHA, but not those of the other 5 resolvins tested, were associated with increased heat pain thresholds (beta = 0.075; 95% CI 0.024, 0.126; p < 0.0046). 17-HDHA was associated with lower pain scores in OA patients (beta-0.41; 95% CI-0.69,-0.12; p < 0.005; adjusted for covariates) but not with radiographic osteoarthritis. The associations of 17-HDHA with heat pain sensitivity and osteoarthritis pain were independent of DHA levels.

Original language	English
Article number	10748
Journal	Scientific Reports
Volume	7
Issue number	1
Early online date	7 Sept 2017
DOIs	https://doi.org/10.1038/s41598-017-09516-3
Publication status	Published - 1 Dec 2017

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Association of the resolvin_VALDES_Publishedonline7September2017_GOLD VoR (CC BY)Final published version, 1.41 MBLicence: CC BY

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Valdes, A. M., Ravipati, S., Menni, C., Abhishek, A., Metrustry, S., Harris, J., Nessa, A., Williams, F. M. K., Spector, T. D., Doherty, M., Chapman, V., & Barrett, D. A. (2017). Association of the resolvin precursor 17-HDHA, but not D-or E-series resolvins, with heat pain sensitivity and osteoarthritis pain in humans. Scientific Reports, 7(1), Article 10748. https://doi.org/10.1038/s41598-017-09516-3

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abstract = "Resolvins are omega-3 fatty acid derived potent bioactive lipids that resolve inflammation and modulate transient receptor potential channels. Exogenous administration of the resolvin precursor 17-HDHA shows a strong analgesic effect in animal models of osteoarthritis and acute inflammatory pain, but has not been studied in humans. Our aim was to assess the role of 17-HDHA and resolvins in heat pain sensitivity and in osteoarthritis pain in humans. Resolvins D1, D2, D3, D5, E1 and 17-HDHA, were measured by liquid chromatography-mass spectrometry and tested for association with heat pain thresholds in 250 healthy volunteers who had undergone quantitative sensory testing. Resolvins D1, D2 and 17-HDHA were then tested in 62 individuals affected with knee osteoarthritis and 52 age matched controls and tested for association with knee pain. Circulating levels of docosahexaenoic acid (DHA) were also measured. Levels of 17-HDHA, but not those of the other 5 resolvins tested, were associated with increased heat pain thresholds (beta = 0.075; 95% CI 0.024, 0.126; p < 0.0046). 17-HDHA was associated with lower pain scores in OA patients (beta-0.41; 95% CI-0.69,-0.12; p < 0.005; adjusted for covariates) but not with radiographic osteoarthritis. The associations of 17-HDHA with heat pain sensitivity and osteoarthritis pain were independent of DHA levels.",

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Valdes, AM, Ravipati, S, Menni, C, Abhishek, A, Metrustry, S , Harris, J , Nessa, A , Williams, FMK , Spector, TD, Doherty, M, Chapman, V & Barrett, DA 2017, 'Association of the resolvin precursor 17-HDHA, but not D-or E-series resolvins, with heat pain sensitivity and osteoarthritis pain in humans', Scientific Reports, vol. 7, no. 1, 10748. https://doi.org/10.1038/s41598-017-09516-3

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AU - Menni, Cristina

AU - Abhishek, Abhishek

AU - Metrustry, Sarah

AU - Harris, Juliette

AU - Nessa, Ayrun

AU - Williams, Frances M.K.

AU - Spector, Tim D.

AU - Doherty, Michael

AU - Chapman, Victoria

AU - Barrett, David A.

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AB - Resolvins are omega-3 fatty acid derived potent bioactive lipids that resolve inflammation and modulate transient receptor potential channels. Exogenous administration of the resolvin precursor 17-HDHA shows a strong analgesic effect in animal models of osteoarthritis and acute inflammatory pain, but has not been studied in humans. Our aim was to assess the role of 17-HDHA and resolvins in heat pain sensitivity and in osteoarthritis pain in humans. Resolvins D1, D2, D3, D5, E1 and 17-HDHA, were measured by liquid chromatography-mass spectrometry and tested for association with heat pain thresholds in 250 healthy volunteers who had undergone quantitative sensory testing. Resolvins D1, D2 and 17-HDHA were then tested in 62 individuals affected with knee osteoarthritis and 52 age matched controls and tested for association with knee pain. Circulating levels of docosahexaenoic acid (DHA) were also measured. Levels of 17-HDHA, but not those of the other 5 resolvins tested, were associated with increased heat pain thresholds (beta = 0.075; 95% CI 0.024, 0.126; p < 0.0046). 17-HDHA was associated with lower pain scores in OA patients (beta-0.41; 95% CI-0.69,-0.12; p < 0.005; adjusted for covariates) but not with radiographic osteoarthritis. The associations of 17-HDHA with heat pain sensitivity and osteoarthritis pain were independent of DHA levels.

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Association of the resolvin precursor 17-HDHA, but not D-or E-series resolvins, with heat pain sensitivity and osteoarthritis pain in humans

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