Novel Research into Opioid Tolerance May Provide Future Pain Relief with Lower Levels of Pain Medicine


Many readers of our readers remember a time early in their chronic pain history when a low-dose opiate, like codeine, relieved a majority of their pain. When I was first diagnosed with degenerative spine disease, I was treated with a low-power opioid medication that is no longer in use – Darvocet-N with 30mg of codeine as needed for breakthrough pain. The Darvocet (containing the opioid medication propoxyphene) was highly effective in reducing my neck and shoulder pain by 75% on average, and one or two Tylenol #3 tablets easily handled any breakthrough pain. That efficacy against pain lasted for years.

Medicine has a term for people who obtain a great deal of pain relief from an opioid analgesic. These people are said to be opiate naïve, and in those days, I was opiate naïve.

Being opiate naïve is a good thing. It means that mild, moderate, and even severe pain can be controlled with low and safe levels of opioid analgesics. One reasons physicians are reluctant to start a patient on a long-term course of opiates is to maintain this state of naiveté, as opioids are the tried and true tool for controlling the pain of trauma and serious disease in medical practice.

As my disease progressed, my pain increased. My medication was adjusted, and when Darvocet no longer worked, my medication was rotated to 60mg of codeine four times a day.

Here’s where the story becomes both complicated and a mystery. To this day my doctors cannot say whether my pain increased due to the degenerative course of my cervical disc disease, or whether the Darvocet stopped being effective against pain because of changes in my nervous system through a process known as opiate tolerance.

With years, my spine continued to deteriorate at multiple levels and as MRI technology because available the degree of cervical and lumbar spine degeneration were revealed as severe. My pain increased and I was prescribed larger doses and rotated to stronger narcotics to control that pain. This process of climbing the opiate ladder of tolerance to the strongest pain medications available in our pharmacopeia occurred over many years, and today my doctors and I struggle with many treatment modalities to manage my pain while keeping my opioid medications as low as possible. I receive, at best, a 25% reducing in pain from my opioid analgesics now, and am disabled with pain.

Long term or chronic opioid therapy (COT) usually follows a course parallel to my journey, and long-time chronic-painers know that eventually their narcotic s will become less effective at managing pain, and they will require larger doses, opioid rotations, or more invasive treatments like nerve ablation or even surgery to achieve analgesia.

Opioid tolerance is hell on earth for chronic-painers and the practitioners who treat them.

Scientifically, opioid tolerance not well understood, but is known to be a property of our complex nervous system. There are many theories regarding how opioid tolerance suddenly “switches on” with COT and why it lowers the efficacy of opioid analgesics used against chronic pain. There is a long history of research on tolerance filled with the mind-boggling esoterics of neurophysiology discussing various molecules, proteins specific to the nervous system, the role of astrocytes and glial cells, neuroplasticity intrinsic to neural tissue, and the myriad other actors relative to research in this field.

Until recently, all research in this area has been performed upon rat subjects, as the methods of research involve inducing pain, treating with large dose opioids, and examining neural tissue through dissection and other means. Certainly no human being would be willing to submit to such a process.

But in a recent study published in Anesthesiology, researchers at the National Taiwan University College of Medicine have identified a specific neural protein directly related to human opioid tolerance.

According to the Department of Anesthesia’s Dr. Chih-Peng Lin, “We found that CXCL1, a protein produced by spinal cord tissue, contributes to opioid tolerance. By neutralizing CXCL1 in patients, we might help solve the problem of opioid tolerance.”

The landmark Taiwanese study was the first to examine tolerance in both humans and rats. Dr. Lin and his colleagues found elevated levels of the protein CXCL1 in both human cancer patients receiving COT and rat subjects deemed opioid tolerant. As part of this study, rats injected with CXCL1 in the epidural space exhibited an acceleration of the onset of opioid tolerance.

Dr. Lin said, “By suppressing opioid tolerance, we can help patients achieve prolonged pain relief without the side effects of increased opioid dosages.”

While this finding is far from being a cure for opioid tolerance, it may be an important piece of the puzzle in solving the causal relationships between chronic pain, COT, opioid tolerance, and opioid induced hyperalgesia, a rare paradoxical finding where treatment with opioids increase pain in some subjects. Eliminating opioid tolerance is an essential achievement in our initiative against pain.

Imagine a world without opioid tolerance, where long-time chronic pain patients maintained on COT can achieve more effective pain control with lower and safer doses of opioids, while new chronic pain patients who respond well to opioid therapy can receive those same benefits for as long as needed.

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EDITOR’S NOTE:  Kurt W.G, Matthies, is a columnist for the National Pain Report.  He lives (and writes) in Colorado. The National Pain Report is interested in hearing your experiences and thoughts.

The information in this column is not intended to be considered as professional medical advice, diagnosis or treatment. Only your doctor can do that!  It is for informational purposes only and represents the author’s personal experiences and opinions alone. It does not inherently or expressly reflect the views, opinions and/or positions of National Pain Report or Microcast Media.

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