Thursday, April 8, 2010

proclus : Michael L. Love: addressing backlash pain

Michael L. Love: addressing backlash pain

There is an interesting phenomenon where pain killers might not work well under conditions I call prostaglandin crash: prostaglandins are already too low for Cox inhibitors such as aspirin, and ibuprofen to have any effect.  This situation could relate to diabetic neuopathy and other types of neuropathy.  It may also relate to the unusual aches and pains that are sometimes experienced by people using calorie restriction (CR) related regimens like resveratrol or the parsley plan described elsewhere in this blog.  In both cases, prostaglandins may be unusually low, but for unrelated reasons, so that some pain treatments might not work. 
Prostaglandin crash is related, and may be the cause of another type of pain, which I call backlash pain.  You might have experienced this when using cough syrup.  Why does dextromethorphan (dxm) analgesia sometimes seem to make the pain or illness worse the next day?  This can also happen with morphine derivatives, and it is certainly related to their addictive potential.
Repressed function sometimes has a strong backlash.  For example, if a glutamate channel antagonist represses calcium release, then the calcium stores may continue to fill, so that there is a stronger activation after the antagonist wears off.  It is not difficult to imagine other types of repression/backlash events, and methamphetamine dependence is likely resulting from something similar as well, leading to dopamine depletion.
There are several possible strategies for reducing pain backlash.  In the case of the calcium stores, IP3 channel inhibition of some sort could prevent the backlash, as well as calcium pump inhibition.  Forskolin is obviously one such agent, which deactivates the IP3 channels.  It should be noted that forskolin also activates the voltage gated calcium channels.  If the calcium blockade results in too much potential, then these channels will open to rectify the situation, as it were, with a calcium transient.  One imagines that forskolin based regimens will not result in the elimination of pain, but rather its attenuation, and a reduction in backlash as well.  This has been consistent with my experience using the forskolin extract from NSI, which is one reason why I am recommending it as an adjunct to CR-related and parsley apigenin regimens.
Personally, there are a number of possible reasons why I am not experiencing pain backlash, and forskolin is likely one.  Another is the time-release formulation of dxm, and finally P450 inhibition by flavonoids, notably apigeinin, which keeps dxm in the system.
So we see that time release calcium channel antagonists is another possible strategy.  Anyone who has used valproate knows what I am talking about.  Another strategy is to identify other sources of calcium influx and repress them as well.  ATP receptor channel leaps to mind, and Blue #1 is apparently an effective agent for that.  In this case, it is extra-cellular calcium influx, like certain of the non-metabotropic glutamate receptors, which form channels.
Calcium influx is not the only issue, and the kinase activation which results from phospholipase activation may also be a source of repression/backlash.
Without anti-inflammatories, repression/backlash can be expected to result in more inflammatory factors being released, via the phospholipase/Cox pathway.  This may be an additional source of backlash.  It should be noted that flavonoids like parsley apigenin and other polyphenols like resveratrol may be sufficitent to suppress a backlash in prostaglandin production, without resort to anti-inflammatories.
In conclusion, a combination of CR-related regimen, dxm, and forskolin should address many pain management problems in a way that prevents the morning-after effect of prostaglandin crash and backlash pain.  Such a regimen may also find application for addiction treatment and recovery.
The blog


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    gnudarwin ようこそproclusさん fun! yesterday reply
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    gnudarwin はてなブックマークはてなブックマーク - proclus のブックマーク @gnudarwin (some small effort) yesterday reply
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    gnudarwin I have an autistic friend, and his allergies have puzzled.. 2 days ago reply
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    gnudarwin proclus : Michael L. Love: parsley and autism: 2 days ago reply
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    gnudarwin parsley and autism, DRAFT, assistance requested. 3 days ago reply
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    gnudarwin Michael L. Love: parsley caveats 4 days ago reply
    Published Thursday, April 08, 2010 01:02 PM by proclus
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