What Would Pain Management Look Like if Opioid Tolerance Could Be Eliminated?

What Would Pain Management Look Like if Opioid Tolerance Could Be Eliminated?

By Staff

There’s a mechanism in the brain that researchers have identified that may well become a target for drugs to prevent tolerance to opioid pain medicine, like morphine, according to a study published in the Nature journal Neuropsychopharmacology.

Scientists from Georgia State University and Emory University demonstrated for the first time that morphine tolerance is actually due to an inflammatory response produced in the brain.  The inflammation in the brain is caused by the release of cytokines, which are chemical messengers in the body that tell the immune system to act up, resulting in inflammation.

By blocking a particular cytokine, researchers were able to create the same level of pain relief with half the amount of morphine – effectively eliminating opioid tolerance (in rats).  That’s correct, equal pain relief with half of the opioids.

This important finding may have critical implications for chronic pain sufferers, who find that because of tolerance to opioid medications, their dosages need to be increased over time, which can lead to less effective pain relief, greater costs, stigma or even the refusal to prescribe or dispense pain medications.  By eliminating the tolerance factor, many pain sufferers reliant on opioids for pain relief may see a path towards more effective, compassionate and necessary care.

“These results have important clinical implications for the treatment of pain,” said Lori Eidson, lead author and a graduate student in the laboratory of Dr. Anne Murphy in the Neuroscience Institute of Georgia State. “Until now, the precise underlying mechanism for opioid tolerance and its prevention have remained unknown.”

Morphine is the primary drug used to manage severe and chronic pain, with 3 to 4 percent of adults in the U.S. receiving long-term opioid therapy.  The problem is that tolerance to morphine, which is defined as a decrease in pain relief over time, significantly impedes treatment for about 60 percent of patients, according to the researchers.

In the absence of pain, morphine interferes with the body’s ability to maintain normal function, which is called homeostasis.  When something interferes with homeostasis the body views it as a disease-producing agent, and the body triggers an immune response to rid the body of the agent.

When Eidson gave rats drugs that blocked the immune response, the rats no longer became tolerant to morphine.

The study also found that tolerance to morphine develops rapidly. Administering one dose of morphine to rats for three days was sufficient to induce tolerance.

“Our findings provide a novel pharmacological target for the prevention of opioid-induced immune signaling, tolerance, and addiction,” the authors concluded.

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Authored by: Staff

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Tiffany Mark

I believe the message they’re sending us is , Learn to live in pain.


I am sick and tired of us with chronic long term pain to have our medications that do help with our pain taken away or tot rated down to levels because of these drug addicts trying to get their high! If these aristocrats sitting in their office come to a conclusion that they are overprescribing to us that have long lasting chronic pain while they have not suffered 1 day of pain I just don’t understand why and how they can do this since they have no idea what we are going
I have been on Opiods for 25 years so don’t you think by now if I was going to become addicted I already would have? I have not slept in a bed for over 6 years due to if I turn on either hip I scream in pain even while the medication is in my system. Let me explain why I need pain medication….. for 25 years I have been suffering with Rheumatoid Arthritis, Systemic Lupus, Heart Disease, Blocked arteries, Interstitial Cystitis, Fibromyalgia, Hypothyroidism, 6 discs bulging in my neck with stenosis and pinched nerves, DDD of neck and spine, Blood clots and Icould go on and on! And these people trying to tell me I don’t need anything for pain. Give me a break. I’m now forced to go in a wheelchair due to having my meds cut so low the pain is so terrible.
A friend I knew committed suicid 3 weeks ago because she was hurting so bad. And I’m afraid there will be more!!!


I am suffering from DDD and other illnesses that cause chronic pain. I have had a complete knee replacement and a complete cervical fusion and complete lower back fusion. I have been in opiates for ten yrs. I got tired of pain management having control over my pain management and when my pm Dr left the clinic 4 months ago and no one seems to know where he went I decided no more pain Drs. I have been off opiates for 10 days now. I take no narcotics for pain. I am using Kratom and marijuana for pain control and it’s working to where I can tolerate my pain. I’m tired of all the hype and lies about opiates. We who suffer and used opiates correctly are suffering from the new rules and suggestions from the DEA and CDC. They want to fix something that’s not broken. Leave it alone! Stop the addicts from getting the drugs. That’s the problem not us. Being addicted and being dependent are two different things. I was dependent not addicted. My back fusion was 10 months ago and I believe it was successful but what people who don’t suffer these chronic pain illnesses don’t understand is that even tho your surgery may have been successful the pain never goes away. We love in pain all day every day. Creating new drugs to stop addiction or tolerance will not help us. Whenever a new drug is introduced in the market there are always new side effects!! Nothing will take the place of opiates. They work! But I refuse to be under the control of dependence anymore. I’m done! I am finding natural pain relievers and eating more healthy and doing all I can to live a fairly normal life

Jean Price

Research for pain care is definitely needed. Yet I would hope the goal of any research would be to effectively reduce pain, not to reduce the dosages of an effective medication already being used for pain care!! So, how will the findings from this study relate to people who already take medications to decrease immune function…like the biologics used by patients with rheumatoid arthritis and a whole group of other autoimmune diseases which cause pain? If this study result is on target and true…then all the people who are currently on these medications should already have great pain relief regardless of the reductions in pain medicines….and I for one don’t find that true in real life….as a non rat!!

I wonder…has anyone looked at the possible issue of INCREASED PAIN over time due to the illness or injury process…and not due to tolerance of the medications? Now that would be something important to correlate and consider…yet with the ongoing primary goal being to decrease pain medications across the board instead of a goal for effective and appropriate patient care, I’m doubting if anyone is interested.

And yes HJ, these immune suppressor definitely do carry the risk of susceptibility to infections, even fatal infections….along with cancer and other major risks!. It would be important not to trade off just simply using a little more pain medication over time…with taking an ADDITIONAL medication offering substantial dangerous side affects!. But then…that is already happening, isn’t it…with the antieplileptic medications and antidepressants so widely being prescribed now to those with persistent pain!! And we all know how well this works for us…or more accurately, how WELL IT DOESNT work for us. I was thinking the other day….if a medication for, let’s say heart disease was being sold on the street and used illegally because it offered a side effect of rapid weight loss if taken, especially in larger than normal dosages, but it also had other dangerous and even deadly side effects…including cardiac damage and altered mental status….would those who have perpetuated this witch hunt on opioids ALSO deny or decrease this medication for the cardiac patients who were helped to live more functionally by it?? I’m thinking NO, unless there were cardiac rehab units in the picture to turn a lucrative profit for them!! Like me, a lot of peoole have a very low level of trust these days and are suspect regarding things related to decreasing (or denying!) the medications for pain we’ve used effectively and in relatively stable dosages for years. Yet, don’t we need to be? Especially considering what has been happening to us for no good reason!! So I’ll wait to see where this study leads us before I jump on the band wagon and deem it good!

If a patient with angina pectoris suddenly needed more nitroglycerin to restore a normal EKG, would the cardiologist babble on meaninglessly about a “tolerance” to nitroglycerin, or would he first look for new vascular problems that might be making the angina worse?

Why, then, do we assume that a patient whose pain feels worse, must be having a tolerance to their medication…instead of first asking ourselves, “What might have just made this person sicker today, than she was last week?”

The difference, I fear, is that for many doctors, “chronic pain” is a dustbin diagnosis, applied to patients they do not understand. They give the patient a label and start treating the patient…not really knowing if the treatment actually helps, because they don’t really know what’s making the patient hurt.

And because they weren’t sure that medicating the patient, helped the patient, when the patient gets worse, they second-guess the previous treatment decision.


I’m currently dealing with tolerance issues. Thanks to the CDC guidelines and political atmosphere regarding pain management I’m being grossly under prescribed and my physicians hands are tied. We have added medical marijuana but the two main issues are #1, after 17 years of opioid combination pain management I’ve developed a tolerance as well as worsening disease progression requiring higher doses #2 my insurance company’s refusal to pay for long addicting medications that would provide sustained relief in combination with medication for break thru pain. The last 17 years we’ve avoided most tolerance issues by rotating opioids which has been highly effective. With the new pain guidelines this is impossible for someone requiring what they consider high dose opiods. It’s terribly frustrating and I’ve become confined to my home again due to pain,

Mark Ibsen MD

This may or may not be about tolerance.
There may be some early onset induction of metabolism or brain inflammation.
Dr Tennant is getting results in tapering by addressing brain glial cells.
Maybe this is similar.
I know that many long term pain patients do not exhibit tolerance.
I think of it as a plateau


I wonder if this means we’ll be susceptible to infections, if it impacts the immune system. The article doesn’t comment on whether or not there are trade-offs. It’s still early in the research process, but there are other ethical considerations besides addiction that may need to be considered.

If the immune system still functions normally when it comes to protection against illness, and if that could be shown and explained to consumers and doctors, then I’d be very glad for the discovery.

Debra McDonald

This is very interesting and it explains why I suddenly stop getting relief with the same meds. My problem currently is that my regular doctor is moving to South Carolina next month and it terrifies me I won’t be able to find a new physician who will continue my prescriptions for chronic pain for peripheral neuropathy, back disorders upper AND lower as well as arthritis in all of my joints. I live in pain every day. I hate to have new MRIS, etc. tests to prove I have been dealing with these issues for over 30 years.

Yvetta Barbee

CBD is good for some patients not so much for others. The THC level in medical marijuana isn’t really what patients who really need is a big factor. The THC is better for high pain levels and to allow the person to relax more which helps with sleep and limits the need for sleeping aides.also limints the need for meds for depression. And medical marijuana ingested limit the affect of constipation. I don’t know how I would have gotten through my first year of illness without it. My pain levels were so high. It was inhuman to live that way. We even put animals down so not to suffer. And yet there is no humanity for humans. That’s a problem.