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Anti-inflammatory effects of kappa-opioids: relevance to rheumatoid arthritis.

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Title: Anti-inflammatory effects of kappa-opioids: relevance to rheumatoid arthritis.
Authors: Walker JS (AUTHOR)
Source: Pain Reviews. Oct2001, Vol. 8 Issue 3/4, p113-119. 7p.
Abstract: Therapy with opioids is an exciting new development for arthritis, especially since there is the potential for fewer side effects from molecules that act outside the central nervous system. We have found -opioid drugs to be powerfully anti-inflammatory, reducing disease severity by as much as 80% and attenuating arthritis in a dose-dependent, stereoselective, antagonist-reversible manner. In contrast, opioids acting at other receptors were therapeutic only at near toxic doses. Currently, however, no pure -opioids are available for clinical use. The hypothalamic-pituitary-adrenal axis was found to be only partially involved; thus we investigated other neural and immune mechanisms. The results showed that the -opioid anti-inflammatory actions were exerted via: (1) reduced adhesion molecule expression; (2) inhibition of cell trafficking; (3) reduced tumour necrosis factor release; and (4) alterations in mRNA expression and substance P (SP) and calcitonin gene-related peptide protein in joint tissue. The ability of -opioids to act at multiple sites in the inflammatory cascade, as suggested by the presence of opioid receptors at various locations throughout the cascade, may explain their powerful actions. -Opioids are, however, most therapeutic during disease onset; thus it is likely they exert their anti-inflammatory effects predominantly via changes in cellular activation and cytokine expression rather than via the nervous system. The involvement of SP and the efficacy of neurokinin 1 (NK1) antagonists predicts that combined opioid-NK1 regimens have therapeutic promise. Peripherally acting opioids may prove to be a potent new treatment for rheumatoid arthritis sufferers in the future. [ABSTRACT FROM AUTHOR]
Copyright of Pain Reviews is the property of Sage Publications, Ltd. 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.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Anti-inflammatory effects of kappa-opioids: relevance to rheumatoid arthritis.
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  Data: <searchLink fieldCode="JN" term="%22Pain+Reviews%22">Pain Reviews</searchLink>. Oct2001, Vol. 8 Issue 3/4, p113-119. 7p.
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  Data: Therapy with opioids is an exciting new development for arthritis, especially since there is the potential for fewer side effects from molecules that act outside the central nervous system. We have found -opioid drugs to be powerfully anti-inflammatory, reducing disease severity by as much as 80% and attenuating arthritis in a dose-dependent, stereoselective, antagonist-reversible manner. In contrast, opioids acting at other receptors were therapeutic only at near toxic doses. Currently, however, no pure -opioids are available for clinical use. The hypothalamic-pituitary-adrenal axis was found to be only partially involved; thus we investigated other neural and immune mechanisms. The results showed that the -opioid anti-inflammatory actions were exerted via: (1) reduced adhesion molecule expression; (2) inhibition of cell trafficking; (3) reduced tumour necrosis factor release; and (4) alterations in mRNA expression and substance P (SP) and calcitonin gene-related peptide protein in joint tissue. The ability of -opioids to act at multiple sites in the inflammatory cascade, as suggested by the presence of opioid receptors at various locations throughout the cascade, may explain their powerful actions. -Opioids are, however, most therapeutic during disease onset; thus it is likely they exert their anti-inflammatory effects predominantly via changes in cellular activation and cytokine expression rather than via the nervous system. The involvement of SP and the efficacy of neurokinin 1 (NK1) antagonists predicts that combined opioid-NK1 regimens have therapeutic promise. Peripherally acting opioids may prove to be a potent new treatment for rheumatoid arthritis sufferers in the future. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Pain Reviews is the property of Sage Publications, Ltd. 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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