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Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetes.

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Title: Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetes.
Authors: Inceoglu, Bora1, Wagner, Karen M.1, Yang, Jun1, Bettaieb, Ahmed2, Schebb, Nils H.1, Hwang, Sung Hee1, Morisseau, Christophe1, Haj, Fawaz G.2, Hammock, Bruce D.1 bdhammock@ucdavis.edu
Source: Proceedings of the National Academy of Sciences of the United States of America. 7/10/2012, Vol. 109 Issue 28, p11390-11395. 6p.
Subjects: Pain, Behavior, Fatty acids, Laboratory rats, Diabetes, Physiological effects of glucose, Toxicology, Neuropathy
Abstract: The nerve damage occurring as a consequence of glucose toxicity in diabetes leads to neuropathic pain, among other problems. This pain dramatically reduces the quality of life in afflicted patients. The progressive damage to the peripheral nervous system is irreversible although strict control of hyperglycemia may prevent further damage. Current treatments include tricyclic antidepressants, anticonvulsants, and opioids, depending on the severity of the pain state. However, available therapeutics have drawbacks, arguing for the need to better understand the pathophysiology of neuropathic pain and develop novel treatments. Here we demonstrate that stabilization of a class of bioactive lipids, epoxygenated fatty acids (EpFAs), greatly reduces allodynia in rats caused by streptozocin-induced type I diabetes. Inhibitors of the soluble epoxide hydrolase (sEHI) elevated and stabilized the levels of plasma and spinal EpFAs, respectively, and generated dose-dependent antiallodynic effects more potently and efficaciously than gabapentin. In acute experiments, positive modulation of EpFAs did not display differences in insulin sensitivity, glucose tolerance, or insulin secretion, indicating the efficacy of sEHIs are not related to the glycémie status. Quantitative metabolomic analysis of a panel of 26 bioactive lipids demonstrated that sEHI-mediated antiallodynic effects coincided with a selective elevation of the levels of EpFAs in the plasma, and a decrease in degradation products coincided with the dihydroxy fatty acids in the spinal cord. Overall, these results argue that further efforts in understanding the spectrum of effects of EpFAs will yield novel opportunities in treating neuropathic pain. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
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  Data: Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetes.
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  Data: <searchLink fieldCode="AR" term="%22Inceoglu%2C+Bora%22">Inceoglu, Bora</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Wagner%2C+Karen+M%2E%22">Wagner, Karen M.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Yang%2C+Jun%22">Yang, Jun</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Bettaieb%2C+Ahmed%22">Bettaieb, Ahmed</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Schebb%2C+Nils+H%2E%22">Schebb, Nils H.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Hwang%2C+Sung+Hee%22">Hwang, Sung Hee</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Morisseau%2C+Christophe%22">Morisseau, Christophe</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Haj%2C+Fawaz+G%2E%22">Haj, Fawaz G.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Hammock%2C+Bruce+D%2E%22">Hammock, Bruce D.</searchLink><relatesTo>1</relatesTo><i> bdhammock@ucdavis.edu</i>
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  Data: <searchLink fieldCode="DE" term="%22Pain%22">Pain</searchLink><br /><searchLink fieldCode="DE" term="%22Behavior%22">Behavior</searchLink><br /><searchLink fieldCode="DE" term="%22Fatty+acids%22">Fatty acids</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+rats%22">Laboratory rats</searchLink><br /><searchLink fieldCode="DE" term="%22Diabetes%22">Diabetes</searchLink><br /><searchLink fieldCode="DE" term="%22Physiological+effects+of+glucose%22">Physiological effects of glucose</searchLink><br /><searchLink fieldCode="DE" term="%22Toxicology%22">Toxicology</searchLink><br /><searchLink fieldCode="DE" term="%22Neuropathy%22">Neuropathy</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: The nerve damage occurring as a consequence of glucose toxicity in diabetes leads to neuropathic pain, among other problems. This pain dramatically reduces the quality of life in afflicted patients. The progressive damage to the peripheral nervous system is irreversible although strict control of hyperglycemia may prevent further damage. Current treatments include tricyclic antidepressants, anticonvulsants, and opioids, depending on the severity of the pain state. However, available therapeutics have drawbacks, arguing for the need to better understand the pathophysiology of neuropathic pain and develop novel treatments. Here we demonstrate that stabilization of a class of bioactive lipids, epoxygenated fatty acids (EpFAs), greatly reduces allodynia in rats caused by streptozocin-induced type I diabetes. Inhibitors of the soluble epoxide hydrolase (sEHI) elevated and stabilized the levels of plasma and spinal EpFAs, respectively, and generated dose-dependent antiallodynic effects more potently and efficaciously than gabapentin. In acute experiments, positive modulation of EpFAs did not display differences in insulin sensitivity, glucose tolerance, or insulin secretion, indicating the efficacy of sEHIs are not related to the glycémie status. Quantitative metabolomic analysis of a panel of 26 bioactive lipids demonstrated that sEHI-mediated antiallodynic effects coincided with a selective elevation of the levels of EpFAs in the plasma, and a decrease in degradation products coincided with the dihydroxy fatty acids in the spinal cord. Overall, these results argue that further efforts in understanding the spectrum of effects of EpFAs will yield novel opportunities in treating neuropathic pain. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1073/pnas.1208708109
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        Text: English
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        PageCount: 6
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      – SubjectFull: Pain
        Type: general
      – SubjectFull: Behavior
        Type: general
      – SubjectFull: Fatty acids
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      – SubjectFull: Diabetes
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      – SubjectFull: Physiological effects of glucose
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      – SubjectFull: Toxicology
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      – SubjectFull: Neuropathy
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              Text: 7/10/2012
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