JCI table of contents: Nov. 1, 2007

Antinociceptive tolerance in mice repeatedly administered morphine was associated with the accumulation of tyrosine-nitrated proteins in the dorsal horn of the spinal cord, increased production of proinflammatory cytokines, oxidative DNA damage, and activation of the nuclear protein poly(ADP-ribose) polymerase. These changes were inhibited, as was the induction of antinociceptive tolerance, if the morphine was administered together with a pharmacological inhibitor of nitric oxide synthesis, a pharmacological scavenger of superoxide, or a pharmacological catalyst for ONOO^- decomposition. Together, these data indicate that ONOO^- has a crucial role in the development of morphine-induced antinociceptive tolerance in mice.

TITLE: Therapeutic manipulation of peroxynitrite attenuates the development of opiate-induced antinociceptive tolerance in mice

AUTHOR CONTACT:
Daniela Salvemini
Saint Louis University School of Medicine, St. Louis, Missouri, USA.
Phone: (314) 577-8856; Fax: (314) 577-8859; E-mail: .

MEDIA CONTACT:
Donn Walker,
Saint Louis University School of Medicine, St. Louis, Missouri, USA.

Phone: (314) 977-8015; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=32420

ACCOMPANYING COMMENTARY

TITLE: When it comes to opiates, just say NO

AUTHOR CONTACT:
Gavril W. Pasternak
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Phone: (646) 888-2165; Email: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=34035

OPHTHALMOLOGY: Macrophages are not all seeing in the eye

Age-related macular degeneration (AMD) is the leading cause of blindness in adults over the age of 50. AMD is characterized by abnormal angiogenesis (the growth of new blood vessels) under the retina. New research using mice by Rajendra S. Apte and colleagues at Washington University School of Medicine, St. Louis, has indicated that as immune cells known as macrophages age they lose their ability to inhibit injury-induced abnormal angiogenesis in the eye.

In the study, macrophages from old mice injected into the eye of mice in which damage to the eye had been induced by exposure to a laser were unable to prevent abnormal angiogenesis. By contrast, macrophages from young mice substantially blocked the abnormal angiogenesis. Further analysis showed that following laser-induced injury to the eye, ocular macrophages from old mice expressed less FasL, TNF-alpha, and IL-12, as well as more IL-10, than those from young mice. The authors therefore suggested that a decrease in macrophage antiangiogenic function upon aging might explain why individuals over 50 years of age are more susceptible to AMD and other diseases associated with abnormal angiogenesis, such as cancer. The broader significance of this study is discussed in the accompanying commentary by Martine Jager and Caroline Claver.