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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 GFRα3 — 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/GFRα3 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 GFRα3 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 GFRα3, preventing artemin from binding to GFRα3 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/GFRα3 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.
More information: Laura Minnema et al, Investigating the Role of Artemin and Its Cognate Receptor, GFRα3, in Osteoarthritis Pain,
Frontiers in Neuroscience (2022)
. DOI: 10.3389/fnins.2022.738976
Reader Comments
Your remark will be ill received by those who fight the brave daily battle of pain.
Fuck 'em if they dont like the truth.
The process of aging exposes the population to a variety of pain signatures, most bearable with a strong mental constitution and other forms of pain management as a support mechanism.
All folk will have there tales to tell regarding pain, all dealt with in many different ways.
Yet lurking out there is pain that not all succumb to and the text books have no answers for and the longing for death is often the way some elect to deal with it.
So please don't be so up your own arse with attitude by Declaring that you know about pain, because you don't. You've experienced pain and your dealing with it and that is to your credit.
If the body is sending pain signals, it is telling you that you are working a joint that is badly damaged. The experiment used mice that had bad OA engineered into them. Eliminating the pain did NOT get rid of the OA, just the symptom, i.e. pain. It's just like engineering an mRNA 'vaccine' that gets rid of the symptoms, but doesn't confer immunity or stop transmission. In short, it serves medical interests in SPREADING disease, not stopping it. These bastards don't make money curing disease, just in prolonging it with more and more medical intervention required down the road. Costly and very profitable medical intervention. Curing disease, as Goldman-Sachs analysts say frequently to Pig Pharma execs, is a very bad business model. You can bet the doctors and Pig Pharma are listening.
The proper way to deal with OA is through DIETARY modification combined with stretching and strengthening supplemental muscular structures, especially for spinal pain. Stop collecting/depositing calcium crystals (e.g., calcium oxalate and calcium pyrophosphate) in your joints from too much calcium in the diet, especially calcium from supplements that overload the body and cause these deposits to accumulate in your inflamed joints leading to (surprise!) even worse OA. I know this all too well, because for years I (like most people) allowed my orthopedists to lead me down the road to worsening OA disease and physical ruin before I wised up to their game. I even had a highly recommended New Zealand ortho tell me to my face that diet PLAYED NO ROLE in arthritic inflammation. That lying greedy scumbag had a waiting room full of other idiots lining up for his 'great' medical 'care'. One visit and I was done with that greedy lying medical jack-ass. But most people are sheeples wanting easy answers and Pig Pharma pills to swallow. No thanks, I'll do it naturally.
The only way this treatment would benefit someone is for those who are so debilitated by OA pain that they cannot even begin the stretching and strengthening routines necessary to take the load off the afflicted joints (especially the spine). However, I can assure you that a pro-inflammatory diet is the real problem behind most all debilitating OA, along with a sedentary lifestyle. It took me being completely unable to walk up stairs and using a cane to ambulate any distance, and worse, being told I would be wheelchair-bound in two years and would need bi-lateral knee replacements if I ever wanted to walk quasi-normally again (which they said was doubtful) to finally decide to do the research necessary to cure my problems myself and not rely on 'medical experts'. That was ten years ago.
Today I can walk ten miles without pain, and it is ALL due to dietary measures, period. Keep sugar strictly out of your diet (very inflammatory!) as well as keep Omega 6 EPAs out as well, and increase Omega 3 by eating appropriate seafoods and taking Omega 3 supplements with every meal, and most importantly, drink at least 1 gallon of mineralized water every day (I drink two gallons per day, every day), to flush calcium and other crystals from your system that accumulate due to, inter alia, oxalate disease, which many suffer from but simply don't know it. I stay away from all red meats and all dark meats from fowl, and if you have no problem with oxalates, a mostly vegetarian diet is best, especially one that stays with tons of green leafy veggies and avoids lots of fruits (sugar again.) Keep it natural and simple. Nature is the voice to heed. Pig Pharma and Pig Medicine? No thanks.......
Good luck to all!