Osteoarthritis

an image of the author’s ankle taken by gamma-scintigraphy. The darker areas show regions of osteoarthritis.Arthritis is a term used to describe several inflammatory conditions affecting joints. As is so often the case with medical history, the name was derived from observed symptoms but subsequently it was found these were the result of a plethora of different causes. Today, “arthritis” covers around 100 different conditions associated with joint disease. Rheumatoid arthritis, for example, is an autoimmune condition, where the patient’s immune system attacks the tissues of joints. Osteoarthritis, on the other hand, is caused by physical damage to joints, particularly protective cartilage. Osteoarthritis has particular interest for me as I am a sufferer. It started with a motorcycle accident when I was in my early 20s and over the years damage to cartilage in my ankles has worsened to the point it can now be difficult to walk for more than a few meters. The condition leads to chronic pain, sometimes severe enough to be debilitating. There are few drugs available to manage osteoarthritis. Sometimes anti-inflammatories have benefit and opioid-type drugs are used to ameliorate pain. Opioids over the long term however, become less effective and have problems of their own.

The reason osteoarthritis is painful might seem obvious. Bones of the joins rubbing on each other, leading to inflammation and sometimes bleeding within the joint. The complexity of biochemistry however, is not something which should be taken for granted. Recent research suggests an unexpected pathway triggers osteoarthritic pain.

Artemin is a protein released from vascular smooth muscle, which then binds onto another protein called GFRα3. One artesian protein binds centrally to two GFRα3 proteins, which triggers nerves acting as relay stations between neurones (known as preganglionic neurons) near to the inflamed joint. This mechanism is already known as a response to heat and cold. If you want to trigger artemin-GFRα3 simply place your hand in a bowl of ice cold water. What’s new is the association of artemin and GFRα3 with arthritic pain. 

Opioid-type drugs bind to receptors in the spinal cord or brain (the three main receptors being known as mu, delta and kappa) and have a generic effect on the sensation of pain. These drugs also cause sedation and euphoria, patients can become dependent and they can have adverse effects on the gastrointestinal tract. If the artemin-GFRα3 pathway effect is confirmed, then this may offer a new more specific target for pharmacologic intervention of osteoarthritic pain, something likely to be welcomed by the 8.5 million suffers in the UK, including me.

Being realistic however, and knowing how long new medications take from concept to market, then I doubt I will see this potential new class of drugs in my lifetime. But all new treatments start somewhere and so perhaps in the next 20-years, we might see some long awaited advances. Non-arthritic fingers crossed.

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