Methotrexate (shown at left) is a very interesting compound. Its history began with FDA approval in 1953 f
or oncology use.It gets the job done by inhibiting folic acid breakdown.
Folic Acid or Folate is water soluble vitamin B9 (pictured right). [Note the similar structural elements of methotrexate and Folic Acid] Folic Acid is broken down to form tetrahydrofolate, a metabolite necessary for DNA synthesis, by the enzyme dihydrofolate
reductase. Due to their similar structure, methotrexate can bind dihydrofolate reductase, block folic acid breakdown, and slow DNA synthesis. This is preferentially damaging cancer and immune system cells as they grow particularly fast and rely on DNA synthesis for their growth.Methotrexate therefore has been used for chemotherapy (high dose) and as a treatment for inflammation associated with the autoimmune response (low dose).
A patient mentioned that Methotrexate relieved her symptoms of Fibromyalgia (a disease defined by chronic pain, abnormal pain processing, fatigue, brain fog, etc...). Why did this happen?
The etiology of fibromyalgia is still unknown. However, methotrexate has been used for a similar disease. Behçet's syndrome is characterized by generalized inflammation that causes ulcers, arthritus, and cardiac problems to a name some symptomes. Behçet's syndrome, like Fibromyalgia, is not well understood. The two diseases have overlapping symptoms of pain, fatigue and cognitive difficulties.
Something still doesn't add up. Methotrexate decreases inflammation and relieves symptoms associated with Behçet's syndrome and yet also pain associated with Fibromyalgia?.
Pain is caused by the activation of a nociceptor (pain receptor) by a mechanical or chemical stimuli. The message is passed by the nervous system through the spinal cord to the brain which responds by understanding the impulse as pain. Inflammation, among a variety of things, is known to cause the release of algesic substances which activate the nociceptors. The pictures comes full circle.
The overlap is there. A compound used for anti inflammatory disease helps with pain in disease states that are associated with inflammation. The difficulty is of course to really know whats happening. The woman who mentioned pain improvement was taking the methotrexate for retinal inflammation and happened to have fibromyalgia.
How do we make this connection faster? Is it smart to push for a clinical trial for methotrexate as a pain treatment when resources in the Fibromyalgia community are limited? Yet, it is these random observations that seem important. I guess thats why these are just some thoughts.
A joke at every end:
A blind man walks into a pharmacy with his guide dog.
He lifts his dog and starts spinning the dog by its leash.
A store employee runs up to the man and asks "hey, what are you doing?"
The blind man replies "just looking around."
1 comment:
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that's coming along with either videos or pictures.
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