Thursday, March 31, 2016

Magnesium vs Drugs

Hours of browsing PubMed is making me delirious, but not yet delirious enough to patronize this film. Moving ahead to a better image:

Where to start? This table relates to yesterday's post about pain, inflammation, nociception, and cytokines. Blue entries indicate biochemical mechanisms that are, when it comes to analgesia, unequivocally beneficial. Red entries are more or less detrimental. The KOR column is green because the jury is out.

KOR stands for Kappa Opioid Receptor. This is one of the subtypes of opioid receptor in the body. It appears to be involved in reductions in pain, and yet is also associated with non-pain dysphoria. The body is complicated and fickle, eh?

MOR is the more familiar Mu Opioid Receptor. This is what opiates, and the opioid drugs inspired by them, bind to. Heroin, morphine, hydrocodone, oxycodone, etc are not created equal, but they all share a strong binding affinity for MOR. They also, frustratingly, lead to its down-regulation; over time they become less effective in reducing pain. In recent years, research has shown that they also bind to TLR4. This is bad because it triggers the release of proinflammatory cytokines, ultimately leading to increased pain and other unpleasant symptoms.

TLR4 is Toll-Like Receptor #4. This is part of the innate immune response. It cannonically  recognizes LPS, a substance on the cell walls of Gram-negative bacteria, a common class of pathogens. Contemporary research also suggests that it responds to various other ligands, such as DAMPs (Damage Associated Molecular Patterns). In short, TLR4 activation signals trouble to the body.

Amitriptyline is a tricyclic antidepressant. I added it to the table because I was pleasantly surprised to read that it is a potent antagonist of TLR4. This fact makes me more favorably inclined towards its somewhat common use in treating fibromyalgia and MECFS.

NMDA receptors are as complex as they are ubiquitous. For the purposes of this post, it suffices to note that they are a key point in the nociception-becomes-pain signal cascade.

Gabapentinoids (Gabapentin and Pregabalin) will be familiar to most fibromyalgia folks. Their primary mechanism of action is to lessen the flow of excitatory Ca2+ along the ion channels of axons. Magnesium ions, Mg2+, also attenuate this signal.

Magnesium is the hero of this story. Information about it abounds (just ask your friend Google). It is commonly deficient in the Western diet. It also has benefits far exceeding those listed in the above table (ask your friend Google). Hopefully, by juxtaposing it with drugs, this post adds some new elucidation. Caveat: the table says nothing of potency - magnesium has a broader spectrum of action than anything else in the table, but it was not pharmacologically designed with a particular aim. It's a Swiss army knife; if you need powerful scissors or a big screwdriver you'll have to look elsewhere. Consequently, if you start supplementing magnesium (as you probably should) don't immediately ditch your meds. I am not a doctor; if you sue me you won't get much money :)

Alcohol is in there for kicks. He's a fun guy, but don't spend too much time with him cuz things will get complicated quickly. In addition to the info in the table, alcohol increases the excretion of magnesium.

LDN - Low Dose Naltrexone! Low Dose Naltrexone deserves a lengthy post all on its own. Fortunately plenty of smart people have already written such posts (ask your friend Google). In short, it's an opiate turned inside-out and upside-down.

Anything I've missed: This post will be updated and refined as needed. At the moment I have a readership of 0 and a brainfog+fatigue of 7. Please leave a friendly comment if you need anything.

Sources: The sources are nonexhaustive, but exhausting; another task I'll defer until I'm recharged. If you're feeling adventurous you can always search PubMed (or your friend Google) for the juxtaposition of two terms (e.g. "amitriptyline NMDA")

Until next time, in the words of SuperBat: 

"So long, and thanks for all the fish"

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