Injury to peripheral nerves (the causes of which include shingles, HIV-AIDS, toxins, alcoholism, repetitive motion disorders, surgery, and cancer) causes neuropathic pain, which differs from ordinary pain and is usually perceived as a steady burning, pins and needles, electric shock sensations, and/or tickling. Normal pain relief therapies do not effectively provide relief from neuropathic pain. Further understanding of the molecular mechanisms underlying neuropathic pain is therefore essential to facilitate the development of new drugs. New research in rodents by Marie Campana and colleagues from the University of California at San Diego, has provided evidence that a fragment of the protein LRP1 (sLRP1-alpha) attenuates neuropathic pain.
In the study, it was first observed that injured peripheral nerves in both mice and rats released sLRP1-alpha into the surrounding tissue microenvironment. Administration of sLRP1-alpha into mouse sciatic nerves prior to injury decreased the levels of injury-induced inflammatory mediators in the local environment and inhibited neuropathic pain. In vitro analysis revealed that sLRP1-alpha modified cells known as glial cells so that they did not respond to the inflammatory mediator TNF-alpha. The authors therefore propose that sLRP1-alpha modifies the response of glial cells to mediators of neuropathic pain and that it might have therapeutic benefit for individuals suffering from neuropathic pain.
TITLE: A shed form of LDL receptor–related protein–1 regulates peripheral nerve injury and neuropathic pain in rodents
AUTHOR CONTACT:
W. Marie Campana
University of California at San Diego, La Jolla, California, USA.
Phone: (858) 822-3767; Fax: (858) 534-1445; E-mail: wcampana@ucsd.edu .
View the PDF of this article at: https://www.the-jci.org/article.php?id=32371
Journal of Clinical Investigation