opioids and DNA changes

[epidural man]

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Is it possible that opioids actually help to maintain a state of persistent pain?

Even a single dose of opioids causes hyperalgesia - that has been shown pretty clearly in the peri-operative setting.

SP Cohen's cool and elegant article showed us that practically EVERYONE on opioids, in a dose dependent fashion develop hyperalgesia.

We know from State of Washington's studies that if a patient gets on opioid on presentation to the ER for back injury/pain, that independently predicts that they won't return to work 1 year later.

We know that opioids act directly on glial cells causing a decrease in spinal pain inhibition, and increases receptor-field expansion.

So, is it possible that giving someone opioids actually makes or helps the pain state persist? If someone has surgical trespass, and is given opioids - and they stay on it longer than would be expected - could the opioids be the culprit in preventing the pain inhibitory system to kick in and do its thing?

 

[101N]

I don't think you need to postulate a DNA change to explain the chronification of CNP. Opioids activate the brain's reward system. Maybe activating the reward system for a long enough period of time 'pull's' pain from the acute circuitry into the emotional circuitry and solidifies it there. Or, even more salient with CNP, maybe the pain was in emotional circuitry to begin with - nobody thought to ask - and introducing chronic opioids just solidified it there.

 

[lobelsteve]

Change in genetics unlikely, predisposed genetics certainly.

 

[emd123]

Is it possible that opioids actually help to maintain a state of persistent pain?

Even a single dose of opioids causes hyperalgesia - that has been shown pretty clearly in the peri-operative setting.

SP Cohen's cool and elegant article showed us that practically EVERYONE on opioids, in a dose dependent fashion develop hyperalgesia.

We know from State of Washington's studies that if a patient gets on opioid on presentation to the ER for back injury/pain, that independently predicts that they won't return to work 1 year later.

We know that opioids act directly on glial cells causing a decrease in spinal pain inhibition, and increases receptor-field expansion.

So, is it possible that giving someone opioids actually makes or helps the pain state persist? If someone has surgical trespass, and is given opioids - and they stay on it longer than would be expected - could the opioids be the culprit in preventing the pain inhibitory system to kick in and do its thing?

It's possible. These are powerful, powerful drugs. They can kill every cell and all the DNA a person has in excess, so I don't find it hard to imagine it's possible, at least possible, there could be some DNA alterations at sub-lethal doses. Also, when using the term "alter DNA" I think you're referring more to "altering gene expression" and turning certain genes on and off. That's certainly possible. It doesn't take much to do that. It's been shown that chronic cardiovascular exercise alters the expression of hundreds of different genes. That's how it makes you healthier, feel better, more relaxed, less depressed, thinner, with stronger heart and lungs. So I don't find it much of a stretch at all, to say that a powerful substance that has a very powerful (even potentially lethal) effect on the bodies pain regulating system, could alter that system in some way.

 

[101N]

Read this article. I think this, rather than DNA changes, explains pain chronification for a majority of CNP. The graph on pg 3049
is impressive.( pm me for a copy)

Eur J Neurosci. 2014 Oct;40(7):3041-54. doi: 10.1111/ejn.12709. Epub 2014 Sep 11.
Rapid dopamine transmission within the nucleus accumbens: dramatic difference between morphine and oxycodone delivery.
Vander Weele CM1, Porter-Stransky KA, Mabrouk OS, Lovic V, Singer BF, Kennedy RT, Aragona BJ.
Author information

Abstract
While most drugs of abuse increase dopamine neurotransmission, rapid neurochemical measurements show that different drugs evoke distinct dopamine release patterns within the nucleus accumbens. Rapid changes in dopamine concentration following psychostimulant administration have been well studied; however, such changes have never been examined following opioid delivery. Here, we provide novel measures of rapid dopamine release following intravenous infusion of two opioids, morphine and oxycodone, in drug-naïve rats using fast-scan cyclic voltammetry and rapid (1 min) microdialysis coupled with high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS). In addition to measuring rapid dopamine transmission, microdialysis HPLC-MS measures changes in GABA, glutamate, monoamines, monoamine metabolites and several other neurotransmitters. Although both opioids increased dopamine release in the nucleus accumbens, their patterns of drug-evoked dopamine transmission differed dramatically. Oxycodone evoked a robust and stable increase in dopamine concentration and a robust increase in the frequency and amplitude of phasic dopamine release events. Conversely, morphine evoked a brief (~ 1 min) increase in dopamine that was coincident with a surge in GABA concentration and then both transmitters returned to baseline levels. Thus, by providing rapid measures of neurotransmission, this study reveals previously unknown differences in opioid-induced neurotransmitter signaling. Investigating these differences may be essential for understanding how these two drugs of abuse could differentially usurp motivational circuitry and powerfully influence behavior.

© 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

 

[drusso]

Don't forget Linda Watkins, PhD work at University of Colorado on glial cell activtation--humans brains basically "see" opioids as xenobiotics...there is variability in phenotype just as there is for practically everything else in medicine.

 

[epidural man]

emd123 - you are correct. I didn't mean to actually say DNA changes - as in mutation, more of expression.

The point being - can whatever state that exists in chronic pain be solidified or even induced when pain exists when opioids are introduced?

101N - cool thought "Or, even more salient with CNP, maybe the pain was in emotional circuitry to begin with - nobody thought to ask - and introducing chronic opioids just solidified it there."