What is breakthrough pain, and what about using medication for it?

Everyone knows that chronic pain continues, and anyone who has chronic pain will tell you that it fluctuates.  Some days are ‘good’ (well…better), some days are …well… not so good.

Some people think of this pain as a new injury‘. Of course, the change in pain is rarely associated with tissue damage, calling it an ‘injury‘ is probably not especially accurate.

Some people call the change in pain acute on chronic pain.  I’m not sure what the ‘acute‘ refers to – acute pain is usually defined as short-term, and is often associated with tissue changes.

And some people call it breakthrough pain, probably drawn from the term used in cancer pain.

In cancer pain the term ‘breakthrough‘ is used to describe episodes of pain that ‘break through’ the pain that is normally allieviated by opioid medication. Despite this seemingly straightforward definition, a recent editorial in the journal Pain stated:

‘the IASP task force on cancer pain found that the definition of breakthroughpain varies widely by country and specialty, even among a group of self-identified cancer pain specialists’ (Markman, 2008)

That editorial goes on to say ‘Breakthrough pain may be related not only to the progression of underlying cancer but also to drug-related phenomena such as under dosing of a long-acting opioid, end-of-dose failure of a long-acting opioid, or escalating tolerance to opioid analgesia. Recent industry-sponsored consensus guidelines reinforce that pain exacerbated by voluntary movements, the so-called ‘‘incident pain,” constitutes yet another form of breakthrough pain.’

The term may be quite ill-defined in cancer pain, but in non-cancer chronic pain it is even more poorly defined. Markman (2008) notes that only one single telephone survey from only nine US pain treatment centers is used as the basis for conclusions about breakthrough in patients without cancer – and only 228 people were participants (Portenoy, Bennett & Rauk, 2006). The findings from this survey indicated that up to 75% of these people experienced fluctuations of pain, that these fluctuations were often initiated by movement (‘incident pain’), and this pain was not especially responsive to opioids. This high proportion of people with exacerbations exceeds the proportion of people with advanced cancer who report ‘breakthrough‘ pain.

I don’t use the word ‘breakthrough‘ when talking about episodes of increased pain.  I’ve called those exacerbations ‘flare-ups‘ because that seems to fairly accurately describe the phenomenon.  What I mean by a flare-up is a temporary fluctuation in pain from the ‘normal‘ baseline. I notice that it appears in both people who use opioids to manage their pain – and those who don’t.

Markman suggests that one reason for the increase in use of this term ‘breakthrough‘ for non-cancer pain may be the role of pharmaceutical companies. This is a provocative statement – but the risks of prescribing opioids for flare-up pain in people who don’t have cancer are very high. Let me explain.

Firstly, even in people with cancer, ‘breakthrough’ pain associated with movement is often not adequately reduced with opioids. This type of pain doesn’t seem to respond to opioids in the same way that cancer pain does. This is partly because of the very rapid onset of this type of pain and morphine and related drugs take a little time to be available in the bloodstream.

Next, while people who are prescribed opiates for pain are typically not addicts, the risk of addiction or habitual over-use of opioids can be increased when the drug is very fast-acting. This is because of the learning effect that occurs when pain (or distress because of, or in anticipation of pain) is rapidly reduced by simply popping a pill. This is positive reinforcement, and it’s powerful.
The fact that there is such a brief amount of time between doing something and obtaining relief strengthens the learning – and if it’s not always effective, this further strengthens the learning effect. If you don’t believe me, think of the gamblers high. Once you’ve won once – the chances of you buying another is much higher than if you’ve always won something, or never won something.

Not only this, people who are prescribed fentanyl for example (a very quick-acting opioid) are, Markman suggests, at especially high risk of developing tolerance to the medication. Tolerance is where, to achieve the same effect, an increasing amount of the drug is needed. Research has found that opiates can increase sensitivity to pain – called ‘opioid hyperalgesia’ – this may drive the increased frequency and dose required to achieve the same pain reduction (Laulin, Maurette, Corcuff, Rivat, Chauvin &, Simonnet, 2002).

So, what about using non-opioids for managing flare-up pain? ie using non-opioids prn (as required).
In my experience, if there is a quick, easy-to-use way of avoiding a negative experience, as humans we’re prone to use it. We learn quickly. This can lead to some really unhelpful and harmful effects of over-use of common medications. For example, one patient told me she used up to 20 paracetamol a day because even though it didn’t change her pain, she felt better for doing ‘something’. She also risked liver damage!

In addition, if there is a simple strategy to use – other approaches that require a little work and need practice will hardly be the first choice.  Even if those strategies are more life-enhancing and give the person the power to choose and cope rather than having faith in something external (internal vs external locus of control).

Some fluctuations have more to do with short-term psychosocial issues than changes to the underlying pain disorder – fatigue, frustration, over-activity, boredom, mood changes, anxiety – all of these can influence pain intensity by increasing distress, arousal, changes to activity pattern.  Medication won’t address these issues.  By not addressing these issues, the ability to withstand life-in-general’s patterns is compromised.

Is it realistic to never have fluctuations in pain? And even if it is, is it helpful to take medications in this way? Do people really come to harm from coping with short-term fluctuations in pain?  Given what we know about how quickly people learn to use something (even if it doesn’t work), the risks of using medication in anticipation of an increase in pain and then overdosing or experiencing negative side effects is very high.  Fluctuations don’t last forever. Like emotions and thoughts, the pain builds up, then ebbs away like a wave retreating from the shore. While it’s not easy to cope when the pain is intense, it helps to remember that pain doesn’t remain at that level forever.

J MARKMAN (2008). Not so fast: The reformulation of fentanyl and breakthrough chronic non-cancer pain Pain, 136 (3), 227-229 DOI: 10.1016/j.pain.2008.03.011

Laulin JP, Maurette P, Corcuff JB, Rivat C, Chauvin M, Simonnet
G. The role of ketamine in preventing fentanyl-induced hyperalgesia
and subsequent acute morphine tolerance. Anesth Analg

Portenoy RK, Bennett DS, Rauck R. Prevalence and characteristics
of breakthrough pain in opioid treated patients with chronic
noncancer pain. J Pain 2006;7:583–91.

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