Researchers identify osteoarthritis `pain pathway'
Date:
January 27, 2022
Source:
North Carolina State University
Summary:
Researchers have discovered that a particular molecular signaling
pathway plays an important role in producing osteoarthritis (OA)
pain. Using a mouse model of painful osteoarthritis, they show
that blocking this signaling pathway eliminates pain and results
in a return to normal limb use. This work is the first to find
an association between this pathway and OA pain, and could lead
to the development of new, effective pain treatments for human
OA sufferers.
FULL STORY ========================================================================== Researchers from North Carolina State University have discovered that
a particular molecular signaling pathway plays an important role in
producing osteoarthritis (OA) pain. Using a mouse model of painful osteoarthritis, they show that blocking this signaling pathway eliminates
pain and results in a return to normal limb use. This work is the first
to find an association between this pathway and OA pain, and could lead to
the development of new, effective pain treatments for human OA sufferers.
==========================================================================
Over 32.5 million U.S. adults suffer from painful OA, making it the most
common joint disorder in the country. The incidence of OA is increasing,
and while it can range in severity, OA can be associated with pain which
limits mobility and function.
"There are currently very few effective and safe long-term ways to manage
OA pain, which is chronic and often very debilitating," says Duncan
Lascelles, professor of translational pain research and management at
NC State and co- corresponding author of the research.
Previously, Lascelles, an expert in companion animal pain management,
and his colleague, NC State neurobiologist Santosh Mishra, observed
increased levels (or upregulation) of the components of this signaling
pathway in the joint fluid, blood and sensory nerves of dogs with
naturally occurring OA. The components in question -- the ligand, or
binding molecule artemin, and its receptor GFRa3 -- were known to pain researchers, but had not been associated with OA pain signaling.
"When you feel pain, that's the result of a molecule at the painful site interacting with a receptor on a sensory nerve, setting off a cascade of
events within the nerve that lead to a signal being produced," Lascelles
says. "This signal travels along the nerve, and is interpreted as painful
by the brain." "For acute pain, the artemin/GFRa3 system has been known
to play a role, particularly in situations like cold hypersensitivity,"
says Mishra, assistant professor of neuroscience at NC State and co-corresponding author of the work.
"However it had not been associated with pain in a chronic condition
like OA.
Observing upregulation of a particular molecule doesn't necessarily
mean it's relevant in a particular condition, so we decided to explore
whether this pathway was functionally involved in pain signaling in OA --
that is, explore whether this signaling pathway was actually contributing
to OA pain." In a mouse model of chemically induced OA the researchers
found that GFRa3 was upregulated in the sensory nerves -- just as it
was in dogs with naturally occurring OA -- versus a control group of
healthy mice. A subset of the OA mice were then treated with monoclonal antibodies designed to bind to GFRa3, preventing artemin from binding
to GFRa3 and effectively blocking the pain signaling pathway.
Within two hours post-treatment with the antibodies, limb function
had returned to normal levels in the treated mice, indicating that the artemin/GFRa3 pathway most likely plays an important role in OA pain.
"While this is a proof-of-concept study, the findings are encouraging
and we hope to continue working to understand this pathway and its
involvement in OA pain," Mishra says.
"Although the work here is in a mouse model, it was based on robust observations in dogs with naturally occurring OA pain," Lascelles says.
"Because OA in dogs and humans is so similar, we believe our findings are highly relevant to both. Hopefully this work can lead to targeted drug therapies to relieve pain in both canine and human OA patients. While we
cannot reverse the joint damage, we can hopefully alleviate suffering
caused by pain, decreased mobility and decreased ability to function."
The research appears in Frontiers in Neuroscience, and was supported by
funding from NC State's Translational Research in Pain Program. Former
NC State graduate student Laura Minnema, and current NC State graduate
student, Ankita Gupta, are co-first authors.
special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> ========================================================================== Story Source: Materials provided by
North_Carolina_State_University. Original written by Tracey Peake. Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Laura Minnema, Ankita Gupta, Santosh K. Mishra, B. Duncan
X. Lascelles.
Investigating the Role of Artemin and Its Cognate Receptor, GFRa3,
in Osteoarthritis Pain. Frontiers in Neuroscience, 2022; 16 DOI:
10.3389/ fnins.2022.738976 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/01/220127104259.htm
--- up 7 weeks, 5 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)