Of Opioids and Pain

The paramedics found their patient unresponsive, his breathing slowed nearly to the point of death. The open bottle of oxycodone, a potent opioid, is what gave them the clue they needed. A single shot of naloxone (Narcan®) revived him very quickly and saved his life. Naloxone completely reverses all of the effects of opioids, including their effect on pain. Patients given naloxone often wake up very angry because their pain, suddenly deprived of opioid, can flare completely out of proportion to the condition that causes the pain. Pain, after all, is one of the symptoms of opioid withdrawal.

There is another medication closely related to naloxone called naloxegol (Movantik®). It is used to reverse the most common side effect of chronic opioid use – constipation. It does this without diminishing the effect of opioids on pain. It is essentially a modified version of naloxone that has been carefully tweaked so that it cannot get into the brain. It travels through the blood to all the parts of the body, reversing all the effects of opioids wherever it goes. Any opioid in the bowel – reversed. Any opioid in the knee – reversed. Any opioid in the shoulder – reversed. Any opioid in the brain – NOT reversed.

What does this teach us about opioids? That they work their pain relieving effects in the brain. Not in the knee. Not in the shoulder. But in the brain.

There is no doubt that the pain felt anywhere in the body can be reduced with opioid pain medication. But we must not lose sight of the fact that the medication being taken is working in a part of the body that was never injured and that is functioning normally – the brain. What does it do there? Well, it’s complicated. But in simple terms it changes the brains interpretation of the signals coming from the injured area. You see - it is the brain that decides whether or not something should hurt. There are several elegant experiments that have proved this beyond all doubt – pain is an output of the brain, not an input from the nerves coming from the injured body area.

Those nerves bring not pain signals, but information about the condition of the tissue. Are they swollen, hot, torn, starved of oxygen, bleeding? All that information and more is brought to the attention of the brain via the nerves that service the injured area. It is the brain that decides whether or not pain would be a useful output to the conscious mind. Sound farfetched?

Consider your own experiences with pain. Haven’t you ever been so engrossed with an activity that you were unaware that you had been injured? Only later, when your brain was no longer engaged with the activity, did you notice the scratch, cut or bruise. There have been instances of soldiers shot in battle who were unaware of their wound until they reached safety. The brain brings us an awareness of pain when such an awareness will not interfere with more pressing matters like winning the game or staying alive. When we are finally aware of the pain, the purpose of the pain is to protect the tissue from further damage. To make us hobble off the field with our sprained ankle. To pull our hand off the hot stove. To seek treatment for tissues that are at risk for further damage if left untreated.

Opioids cause the brain to misinterpret the information it is receiving from the tissue as being less harmful than it really is. They are in a sense poisoning the brain’s “pain meter.” Now remember, the “pain meter” was not broken. But now, with opioids present, it is no longer accurate. It no longer is accurately gauging the potential for further harm. If the opioid user is not careful, they can cause severe injury to themselves when under the influence of opioids. But with appropriate precautions most people benefit nicely from the opioids given briefly for acute pain.

The outcome with opioids and chronic pain is much different, however. The “pain meter” gradually adjusts to the effect of the opioid. We call this tolerance. Tolerance causes the “pain meter” to begin reporting the pain more and more accurately again. Painful things are painful again. But with the opioid absent – boy oh boy – watch out. The pain spikes through the roof. The “pain meter” swings wildly to the side of over-reporting the pain. Now, with the “pain meter” malfunctioning because of tolerance, not only does the person have withdrawal pain (they hurt everywhere) but they also have unnaturally high injury pain – the injured body part hurts like the proverbial hot place.

Does this mean that opioids shouldn’t be used for chronic pain? The answer is again complicated, but in general, because of tolerance, opioids should not be used for chronic pain. If you are someone who has suffered an injury or condition that has resulted in persistent pain, then please seek alternatives to opioids. Your life will go much more smoothly if you avoid opioids. If you are already taking opioids, and have been on them for many years, the answer is less certain. We do know that in every single scientific study in which it has been tried, reducing the dose of opioid results in an overall improvement in the pain. What we don’t know is whether or not they can be stopped completely. This should be an individual decision between a patient and their doctor. 

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