Chronic Pain After Cancer: The Role of Opioids – part 1

Chronic Pain Following Treatment for Cancer: The Role of Opioids – Ballantyne – 2003 – The Oncologist – Wiley Online LibraryJane C. Ballantyne –  Dec 2003

This study was done just months after Ballantyne had authored a study claiming hyperalgesia is a common problem with continued opioid use.

Ballantyne is one of the most adamant anti-opioid zealots who now insists that “opioids are bad” under all circumstances and shouldn’t be used for chronic pain, but in 2003 she was apparently still reasonable.

Opioids are the most effective analgesics for severe pain.

opioid tolerance, if it develops, is relatively easy to overcome, and other problems of opioid use, including substance abuse, are unlikely to be problematic.

So, in 2003, she believed that opioid use is unlikely to be problematic, a view directly opposed to her current position. We never see references to these positive findings of opioid use anymore.

increasing numbers of cancer patients experience long remissions, chronic pain due to cancer, or to cancer treatment, becomes a clinical problem that oncologists will encounter. In the case of chronic pain, functional restoration is a predominant goal of treatment. 

If opioids are chosen, tolerance, dependence, and addiction can interfere, and safeguards designed to minimize these must be built into the treatment plan

This article reviews the principles of chronic opioid therapy for non‐cancer pain and how these principles may be adapted for patients with chronic pain due to cancer.


The terminology used in pain practice deliberately separates dependence from addiction, since physical dependence is an inevitable consequence of continuous opioid use that is rarely associated with aberrant behavior when opioids are used for the treatment of pain.

Substance dependence, as defined in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM IV), may include

  • tolerance,
  • physical dependence, and/or
  • various aberrant drug‐seeking behaviors,

while substance abuse

  • does not include tolerance, physical dependence, or compulsive use, but
  • is a term used to describe harmful drug‐seeking behaviors specifically.

Figure 2
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Definitions related to the use of opioids for the treatment of pain

Opioid Tolerance and Opioid‐Induced Abnormal Pain Sensitivity

Opioid tolerance is a pharmacological phenomenon that develops after repeated opioid use and necessitates an increase in dose to maintain equipotent analgesia.

Pharmacological tolerance is largely a cellular adaptive process that involves downregulation (reduced number) and/or desensitization (reduced sensitivity) of opioid receptors [1011].

As basic scientists elucidate mechanisms of pharmacological tolerance, it becomes clearer that  an increased opioid requirement, assuming there has been no disease progression, does not always indicate simple pharmacological tolerance.

I’ve now started underlining all the words used to blur the findings, making them seem dubious or unclear, and obscuring any outcomes showing opioids to be effective, useful, and safe.

Repeated opioid administration results in the development of tolerance (a desensitization process), but may also lead to a pronociceptive process (a sensitization process).

Abnormal pain sensitivity has been observed in association with opioid administration in both animals and humans [1315].

Here we go with the hyperalgesia theory (established by observation of an association, not outcome or causation), which is far from an established fact in humans. I checked the citations (1315) and they were old, even at the time this article as written in 2003:

13  J Mao, DD Price, DJ Mayer. Experimental mononeuropathy reduces the antinociceptive effects of morphine: implications for common intracellular mechanisms involved in morphine tolerance and neuropathic pain. Pain 1995; 61: 353– 364.
14  RA Brodner, A Taub. Chronic pain exacerbated by long‐term narcotic use in patients with nonmalignant disease: clinical syndrome and treatment. Mt Sinai J Med 1978; 45: 233– 237.
15  SR Savage. Long‐term opioid therapy: assessment of consequences and risks. J Pain Symptom Manage 1996; 11: 274– 286.

Opioid‐induced abnormal pain sensitivity may exacerbate and confound pharmacological tolerance, although the relative contribution of these two processes remains unclear.

Unclear? You’d never guess that from how this article is written, especially when “the relative contribution of these two processes remains unclear”.

Thus, apparent opioid tolerance may be the result of pharmacological opioid tolerance, opioid‐induced abnormal pain sensitivity, and/or disease progression.

At present, it is not clear whether opioid‐induced abnormal pain sensitivity is related to dose, individual opioid, route of administration, length of administration, or other factors.

Nevertheless, the phenomenon may, at least in part, explain the failure to relieve pain in some patients, despite upward titration. Thus, in some instances, pursuing increasing pain with increasing opioid doses might be counterproductive.

Principles of Chronic Opioid Therapy

Addiction does not appear to be a problem when treating acute or terminal pain with opioids, but can develop during chronic pain treatment, especially in patients with a history of substance abuse.

Whatever happened to this clear statement that “Addiction does NOT appear to be a problem”?

Just a few years later she began advocating for opioid restrictions, and these days suggesting restrictions even for acute and post-surgical and cancer pain.

Estimates of the incidence of addiction in patients treated with opioids for chronic pain range from 8%–17%, differences being due to

  • differences in definition,
  • as well as in the populations under study, and
  • in the reporting physicians’ approach to treatment

Even though patients with chronic pain due to cancer differ in some respects from patients with nonmalignant/noncancer pain, understanding the principles of opioid management in chronic noncancer pain can be helpful in the management of chronic cancer pain. Differences are outlined below.

Patients embarking on chronic opioid therapy need to understand its likely benefits and risks and agree to all that is involved in the commitment to long‐term opioid therapy, including intensive follow‐up and monitoring.

The natural history of chronic pain in patients with cancer differs in that it is often one of severe pain during the initial phases of treatment, followed by chronic, less severe pain during remission.

Thus, cancer patients start opioid treatment during their curative treatment, and if they develop chronic pain, the opioid treatment is continued.

Here you can see how old this article is; nowadays cancer survivors are routinely forced to stop taking opioid medication regardless of their lingering pain.

Many cancer patients already carry prejudices against opioids, and the focus tends to be on persuading them to accept opioid treatment, rather than on stressing the risks.

Many patients have to be pressured to take opioids, even when clearly appropriate because they are so afraid of “becoming addicted”, thanks to the relentless blare of anti-opioid rhetoric of the media.

This resistance to opioids is clearly not a response from someone who is “drug seeking”.

The point at which the treating physician recognizes that pain has become chronic rather than acute, and that survival is likely to be prolonged, is also a good opportunity to explain the benefits and risks of long‐term opioid therapy, and document the conversation, if this has not already been done.

It is helpful to explain that there is a risk of addiction, albeit small, but that careful follow‐up and frequent prescription renewals will be used precisely so that addiction does not develop.

How often a prescription must be renewed cannot stop anyone from becoming addicted.

If an addiction is triggered, opioids will become more necessary to feed it. If they want more opioids than prescribed, such a patient will just buy opioids on the street in the form of:

  • counterfeit pain pills,
  • heroin, or
  • any illicit powder (heroin, cocaine, amphetamine, etc.) cut with a bit of illicit fentanyl.

In general, an important goal of therapy for chronic pain is functional improvement, whereas in terminal illness, the primary goal is symptom relief. Obviously, the exact functional goals will vary according to the patient’s degree of disability.

If goals vary according to the patient, why is it OK to standardize ALL opioid doses regardless of the patient’s needs?

Patients should understand that chronic stable opioid therapy does not impair cognitive function or the ability to work, drive, or operate machinery [3234],, and

may even improve cognitive functioning when compared with functioning under conditions of uncontrolled pain [26].

These crucial points are completely forgotten or censored nowadays, yet they are what pain patients have been reporting all along.

These arguments strongly support chronic opioid therapy and back in 2003, Ballantyne seemed to understand that.

I wonder whatever made her transform into such a rabid anti-opioid zealot.

To be continued…

This has been a lot of work, combing through this long article and finding out how reasonable Ballantyne used to be. I’ll continue the rest of the article in tomorrow’s post.

6 thoughts on “Chronic Pain After Cancer: The Role of Opioids – part 1

      1. Zyp Czyk Post author

        I admire Darnall for so publicly changing not only her own stance, but actually pushing for better treatment of pain patients. I see it as correcting a course she saw was far more draconian and cruel than she intended/expected. That takes courage, which is exactly what so many others lack these days.

        Liked by 1 person

  1. Phyllis A Lane

    I have Ehler’s-Danlos Syndrome. We don’t metabolize opioids. I just had another urine test and my Fentenyl does NOT show up in my urine nor blood. I think I am wasting time and money. Want to try Kratom.

    Liked by 1 person

    1. Zyp Czyk Post author

      I have EDS too, but opioids work pretty well for me – eventually. It’s not EDS that causes problems with opioid metabolism, but a different genetic quirk relating to the P450 Cytochromes which are the enzymes that metabolize opioids.

      EDS causes so many unusual and painful symptoms that there’s a tendency to blame every one of our health problem on that but in this case, it seems to be a separate issue with opioid metabolism.

      Liked by 1 person


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