Expecting bad things – what are the repercussions?

I am currently on the train to Wauchope, NSW to visit my husband who is doing a rural medical placement. Now in my head, I decided that train food would be shocking and so when low and behold, I got my meal, I was pleasantly surprised to discover that it was not only edible but quite…delicious?  I know! It knocked me for one too. However, this is something that I’ve noticed – if I don’t have high expectations of things, I am often pleasantly surprised and it makes for a happy day. However, if I expect everything to be amazing then I’m constantly disappointed (like when your friends tell you it will be the best movie ever…).

So how surprised was I to discover that expectancy seems to play the opposite role in terms of pain – eg, if you expect/believe/are conditioned to expect a stimulus to be less painful, it usually is less painful. A recent narrative review in Neuroscience Letters from Atlas and Wager has amalgamated the literature (mainly experimental) on the role of expectancy in pain.[1] This fab review considered placebo responses (eg, expectations that a treatment will cause pain relief, even though the treatment is inert, results in pain relief), nocebo responses (eg, increase in pain that accompanies beliefs that a treatment will cause pain or increase symptoms), and stimulus expectancy effects (eg, expectations about noxious stimuli that can be elicited through instructions or arise from spontaneous inferences or can develop though associative learning processes – see Daniel’s post on classical conditioning!). What this review does is give a great overview of the various responses, body systems, and brain and spinal cord regions possibly involved or related to expectancy. Now what I plan to do is just cherry pick a couple of points that I hope will raise some discussion.

My first point relates to the expectancy effects in experimental pain versus clinical pain. First, it is well-established that the placebo effect occurs in clinical conditions (see classic review here[2]).  However, much of the brain imaging data that provides the neurobiological link between pain reports and actual changes to the nociceptive circuitry comes from experimental pain studies (note: the review[1] does present some interesting data on irritable bowel syndrome[3] and fibromyalgia[4]). Certainly there are many practical reasons for this, but the fact remains that we would likely expect somewhat different responses in people with chronic pain than with experimental pain. Therefore while these studies definitely give us a much better understanding of the role of expectancy in experimental stimuli, we are lacking crucial research into clinical pain. I posit that this becomes particularly important when we consider the difference in emotional impact between pain that is transient vs pain that you don’t understand and that doesn’t go away.

My second point relates to how we develop theories regarding expectancy and pain – specifically how we base a lot of theories on correlations. We often assume the relationship between 2 variables goes one way or another (ie, inappropriately inferring causation). First, assuming causation is not the way to go, but regardless, we tend to speculate the direction of a possible relationship because it helps us design future studies. So what if relationship direction that we choose is wrong? For example, we find that people who tend to have the best responses to placebo have higher levels of trait optimism.[5] Thus there is a tendency to think, if I just become more optimistic, I will get a better response to placebo (kindly ignore the complete oversimplification of optimism being the only factor related to a robust placebo effect). However, what if the relationship was actually in the other direction? What if all my life I just tended to have good responses to everything (eg, my brain worked differently and processed information differently) and so I became quite optimistic, because in fact, for me, any treatments for pain always ‘worked’. Then we have mistakenly given optimism a key role in placebo response vs inherent differences in brain processing of noxious stimuli being the key. Please note that the review did not suggest this but it was just something that made me think.

What would be fascinating to me would be to run a longitudinal study where we image people and then follow them for ages (ie, until enough develop chronic pain) and then re-image everyone. At baseline we could image cortical responses to a noxious stimulus and cortical response when we induce positive expectations (ie, pain relief) for experimental pain. Then when we can image the same things once a person has developed chronic pain which would allow us to compare their ‘new responses’ to their ‘old responses’. We could also image cortical activations during their chronic pain and also activations in response to a placebo treatment aimed at their chronic pain, allowing us to evaluate differences between chronic pain and experimental pain (in one person). I think a longitudinal study would allow us to create a better overall picture. Anyone have some spare pocket change?

So based on this review paper[1], I come away with a healthy respect for the role of expectation in pain. However, regardless of the results of this review, I think I’ll stick with having no prior expectations going into movies…the alternative is just too disappointing!

Tasha Stanton

Tasha Stanton Body In MindTasha Stanton is a postdoctoral research fellow working with the Body in Mind Research Group both in Adelaide (at University of South Australia) and in Sydney (at Neuroscience Research Australia). Tash has done a bit of hopping around in her career, from studying physio in her undergrad, to spinal biomechanics in her Master’s, to clinical epidemiology in her PhD, and now to clinical neuroscience in her postdoc. Amazingly, there has been a common thread through all this hopping and that common thread is pain. What is pain? Why do we have it? And why doesn’t it go away?  Tasha got herself one of the very competitive Canadian IHR post-doctoral fellowships and is establishing her own line of very interesting investigations.  Her research interests lie in understanding the neuroscience behind pain and its clinical implications. She also really likes nifty experiments that may have no clinical value yet, but whose coolness factor tops the charts. Last, Tash is a bit mad about running, enjoying a good red with friends and organizing theme parties. Tasha, aka Stanton Deliver, was the all round best performer at the Inaugural BiM Table Tennis Comp. Here is Tasha talking more about what she does and a link to her published research.

References

[1] Atlas LY, Wager TD (2012). How expectations shape pain Neuroscience Letters, 520, 140-48 DOI: 10.1016/j.neulet.2012.03.039

[2] Beecher HK. (1955). The powerful placebo. Journal of the American Medical Association, 159, 1602-606 DOI: 10.1001/jama.1955.02960340022006

[3] Price DD, Craggs J, Verne GN, Perlstein WM, & Robinson ME (2007). Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients. Pain, 127 (1-2), 63-72 PMID: 16963184

[4] Goffaux P, de Souza JB, Potvin S, & Marchand S (2009). Pain relief through expectation supersedes descending inhibitory deficits in fibromyalgia patients. Pain, 145 (1-2), 18-23 PMID: 19524367

[5] Morton DL, Watson S, El-Deredy W, Jones AKP. Reproducibility of placebo analgesia: effect of dispositional optimism. Pain 1999; 80: 1-13.