Editorial from PAIN: Hijacking the endogenous opioid system


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Neuropathic pain responds poorly to opioids, often not at all, and may become worse with treatment.

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I have seen pain improve in many after tapering off.

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Then you must treat pain without opioid; it doesn’t just disappear, but it will not be as intense. This editorial explains some of the reasons opioids become a problem.

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Excerpted from an editorial in the current issue of PAIN

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[emphasis mine]

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[COT = chronic opioid therapy]

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…..This review highlights why we may see some of the more insidious problems that occur with COT, which are summarized below.

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Individuals on COT may continue to “need” opioids to replicate the functions of endogenous opioids that are no longer being released (or are in competition with the exogenous opioids). As the review by Ballantyne and Sullivan states, “a new homeostasis is reached that can only be maintained by continued drug taking”.1 Individuals on COT lose the ability to endogenously improve mood, decrease stress, and socially engage because the endogenous opioid system becomes inherently less responsive. In pain management, we know of this need for increasing opioid dose over time to maintain analgesia as opioid tolerance. But a similar physiological phenomenon likely occurs with any endogenous opioid function. Although we have mainly anecdotal reports from individuals who have been weaned off of opioids, the change in personality, social engagement, motivation, fatigue, and mood is often profound when individuals on COT successfully taper to lower doses or off opioids. These insidious side effects of COT would all be expected to inhibit individuals from maximally engaging in the patient-centric, disease management strategies that are now recommended for all chronic pain states.

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This may also explain why it is often very difficult to taper individuals on COT completely off opioids and underscores the importance of a slow, structured weaning protocol with appropriate psychological support. It may take months or years for endogenous opioid function to return to normal after cessation of opioids, or perhaps this system never returns to normal in some patients (as seems to occur in heroin addicts).5

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This paralysis of the endogenous opioid system by COT could render ineffective many other treatments that are recommended for chronic pain and that work in part via the endogenous opioid system. Many if not most nonpharmacological therapies for pain, such as exercise, acupuncture, and many other mind-body therapies are believed to work in part by engaging endogenous analgesic pathways that are partly opioid dependent.

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Opioids have acute antistress and antidepressant effects, and many of our patients with chronic pain are taking opioids chronically to medicate their co-morbid depression, despair or distress more so than to treat pain. Brain imaging studies indicate that many brain regions typically involved in pain and sensory processing are also involved in affective regulation. Patients having chronic pain who show higher degrees of psychological comorbidity or stress might therefore desire opioids because of their temporary salutary effects on these domains, rather than for their intended analgesic effects. We need to develop better cognitive-behavioral and psychosocial interventions that target the needs of the many patients with pain experiencing more harm than benefit from opioids, but still seek these drugs to reduce their affective symptoms.

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The endogenous opioid system may actually participate in the pathogenesis of some chronic pain conditions making this class of drugs particularly problematic for some patients. Many lines of evidence suggest that individuals with more centralized pain conditions such as fibromyalgia are particularly unresponsive to opioids, and the endogenous opioid system may be participating in the pathogenesis of these conditions.2,7 This has tremendous clinical implications because it means that we may actually make these patients’ pain worse by administering opioids. These same individuals may also be those at highest risk for prolonged use of opioids initially given for acute pain, both because they need higher doses for longer durations, and they are more likely to have the psychological comorbidities that drive unintended use and misuse.

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We clearly need to re-think the focus of opioid education and screening programs in light of some of these observations. After any exposure to an opioid, especially following the very common use in the United States for treating acute pain, patients can become addicted or can misuse these drugs to treat concomitant despair, depression, or pain elsewhere in the body that would not be expected to be responsive to an opioid. As we contemplate risk evaluation and mitigation strategies to curb further opioid misuse and addiction, we need to better appreciate these common alternate paths to unintended uses of opioids.

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We are not the first field to underappreciate the consequences of hijacking a critical endogenous system for one purpose, only to eventually find that there are significant consequences. Following the discovery of the endogenous corticosteroid system, Hench and others found that cortisone was an extremely effective treatment for rheumatoid arthritis, and this revolutionized our treatment of inflammatory processes. But it took several decades to fully appreciate all of the intermediate and long-term side effects of chronic corticosteroid use.4 Nearly all of these under-recognized issues were due to off target effects of exogenous corticosteroids on critical endogenous functions of these hormones. Although the short-term effects of opioids have been understood for centuries, long-term, high-dose opioids have only been advocated for a few decades. It is likely that we are now witnessing a similar clinical phenomenon, and as we increasingly appreciate the off-target effects of repurposing a critical endogenous system, the pendulum needs to rapidly swing back towards caution with prescribing a class of drugs that have a plethora of serious side effects other than addiction and death from overdose.

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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4 Responses to “Editorial from PAIN: Hijacking the endogenous opioid system”

  1. Rick Says:

    Until there is an improvement in pain meds pls stop your opiate bashing. For some with multichannel intractable pain, it’s all we have to even get up off the couch to PT.

    You really don’t see this, do you?

    Respectfully,

    Rick

    • Nancy Sajben MD Says:

      This is state of art science on opioid responses triggered in the brain and implications for figuring the hell out of this mess we’ve caused with opioids, and get some real interest into pain research.

      There is no interest. None. Pharma walked away form pain research years ago – I posted on that recently, excellent detailed work reported in Bloomberg News this fall. NO INTEREST IN TREATING PAIN. BAREST “NOTHING” RESEARCH FUNDING FROM NIH.THERE IS NO INTEREST.

      You, Voter! Get congress to stop funding billions in research that goes free to Big Pharma so they can charge $100,000 or half a million on their next nothing drug ….. but not for pain. They walked away from the field years ago.

      —-DEHYPNOTIZE YOURSELF—

      All of us. Do something, don’t just write to me. Take action!

      And if you care about the blasted swamp, vote and get out your car to drive as many people as you can to the voting booth.

      Take charge. And please don’t bash your doctors who are HYPNOTIZED BY INDUSTRY. BILLIONS of DOLLARS OR MORE EACH YEAR from SPINAL CORD STIMULATORS, BILLIONS FROM OPIOIDS.They are happy as pigs wallowing in the mud. No accountability, no research — e.g., let’s see some hard data on incidence of complications from the stimulators including how many with CRPS had massive flare of pain and spread in areas of nerve pain — and please sort two groups: those ON opioids bec we already know opioids cause pain, so separate this group. and the other group those OFF opioids. Study all sorts of pain treatments, e.g. acupuncture, massage, P.T., biofeedback, cognitive behavioral psychology and glial modulators. Long term study 2 to 5 years. We already know once opioids are started, patient is far less likely to ever return to work. That’s tragic, to lose the ability to work. I’m in my 70’s and I wanted to work til 80. Work is a blessing.

      Nothing and nobody (industry, pharma, NIH, congress) gives a hoot for treatment of pain.

      We are headed back to 1980’s, the few tools we had then …… except the multibillion dollar industry of spinal cord stimulators. They may cut off opioids – dwindling doses down and not starting new people. New patients with chronic pain will not get any — they don’t even have to take yours away. Just close off access to newly disabled. This is just the beginning and has nothing to do with people in pain who are not addicts. I think CDC is too lazy to even explain the science. Why should they take one minute? By fiat they practice pain management because the epidemic is killing families all over the country. They don’t waste their time, just cut the dose and squeeze supply.

      But this type of article is exactly what makes us think and rethink, what have we done? What happens to the opioid made by the brain itself, and all sorts of other symptoms the brain is no longer functioning. You are not yourself. Sad. And we know how opioids cause pain. We know the science, for a long time. Instead what seems to go for the common standard of care throughout the land is the opposite.

      The country is entrenched in an opioid paradigm. You cannot change a paradigm quickly. That’s why I posted instructions to doctors who want to try a better paradigm, at least for many who failed opioids, failed every ketamine coma, failed every known invasive treatment. To those who care, take action. Use the work here of the last 7-1/2 years. Use the search function top left. Ask your doc to call me to schedule 3 hours telephonic training. I do not want to hear from patients. I am not going to talk your doctor into anything – I will train if they want.

      How many babies have you followed immediately after birth from a mother on low dose morphine for chronic pain?

      How many births do you think are occurring today across the country among mothers taking prescribed low dose opioid and the births among mothers with addiction to maybe all sorts of drugs? Tens of thousands each year? I don’t know birth rates but I am shocked at the % of people taking opioids and their doses. Mothers wait til their 40’s for first birth, by then how many disabilities – low back pain, knee pain? migraine? – how many conditions do they have requiring morphine?

      All those developing brains that for 9 months have had their entire endogenous opioid system destroyed.

      How many of those babies have you seen?

      Go visit a neonate unit sometime and tell me this country must not pay attention to science, NOT spend another penny for true pain control. People on opioids maybe just want to let pharma and industry continue on the same road. Don’t even think or do research – it rocks the boat??? Are we that in love with our opioid and afraid of pain to say ignore science? If I had bad pain, I may feel the same, but we must push science forward for better relief.

      This opioid paradigm is what happens when no one invests in pain research and lets pharma control the field. I hope we can all think about implications of opioid use on the large scale of millions.

      And take action to demand Social Security Administration include some pain syndromes under some circumstances for disability — they do not give disability for pain! I recently learned that! decades in the field, I did not know why all pain patients get denied. We all know pain doesn’t get in the way of a job, right?

      It’s hard to care about a system so rotten to the core. The corruption of industry so deeply worshipped. The opioid paradigm. When y’al get tired of it, realize their only interest is to make it unaffordable for the middle class so it gets denied by PPO and taxpayers end up enriching their multi-billion dollar drugs.

      But it is unaffordable for the average middle class person to undergo the the outpatient costs of compounded medications and costs of medications not covered because they are off label. Science says Namenda to block the NMDA receptor to reduce pain – same mechanism as ketamine, but FDA approved only for dementia. Then prescribe double the dose – refused, refused, refused. Most drugs are refused. P.T. is limited. It goes on.

      Insurers potentially could invest in the things I teach.

      Ain’t gonna happen. Ain’t holding my breath. I wish you all the very best. Be strong! My heart goes out to anyone in pain.

  2. Jerry Wilson Says:

    Thank you, learning so much from you & common sense .


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