Blog 17: Harnessing placebo – “When I say whoa, I mean whoa!”

I recently attended an interesting two day symposium organised by the University of Sydney using the following banner:

The “harnessing placebo mechanisms” slogan was elaborated on in the stated aims of the symposium as “improving outcomes by augmenting the influence of the therapeutic context”.

It has long been my view that perceived responses and measurable biological responses that are induced by context, meanings, beliefs and expectations are a pivotal part of the chronic pain puzzle. I therefore found this symposium attractive. It contained a range of enlightening presentations providing  exacting, academic perspectives as well as  ‘left field’  views on these processes which are mostly still known as ‘placebo’ and ‘nocebo’ responses. Several presenters at this symposium have featured prominently in my self-education journey over the past decade or so. In addition to the large number of relevant journal articles encountered in this journey, there is a comprehensive text titled – “Placebo and Pain – From Bench to Bedside” which is heavy going in parts but worthwhile.

The symposium began with a presentation by one of my co-authors , Associate Professor Damien Finniss who has come a long way since his interest in placebos was first stimulated by forgetting to turn on the power switch to the ultrasound machine while working as a team physiotherapist.  His final slide was a reminder that our worlds are filled with things that influence our beliefs, preferences and expectations; something marketing professionals have long recognised to great advantage.

The academic approach to placebo research was headlined by Associate Professor Luana Colloca, with world renowned credentials in this field and the lead author of the text referred to above. She presented many impressive research based conclusions on the potency of placebo and nocebo processes. Importantly, she informed that negative nocebo responses were faster and more easily induced than positive placebo responses in those who are vulnerable. Both were modifiable by “expectation violations”.

A particularly entertaining presentation was provided by Professor Daniel Moerman, an American Anthropologist. This was done during dinner and was ingested alongside several excellent wines after a long day in the academic (harnessed) saddle. I was fortunate to have Daniel at my wife’s and my breakfast table for discussion a few days later after the conference had finished. Daniel provides the perspective that the terms placebo and nocebo are redundant, and largely unhelpful, because achieved responses are due to the complex meanings that are derived throughout our lives from multiple sources.  Indeed, they have little to do with the inert things that are eagerly provided, and are misleadingly perceived, to be the significant component of the process. He supported this viewpoint with his top 10 research studies. The study that stood out was that of a rise in Chinese cardiac mortality on the fourth day of the month coinciding with an entrenched cultural perception that the number ‘four’ is unlucky because it is only varied in meaning from the word for ‘death’ by a different intonation.

At our breakfast discussion Daniel advised me of the polarising rift in the placebo research community because of this fundamental disagreement. This reminded me of a similar opinion communicated by a comrade pain revolutionary, and pain academic, Steve Kamper. Steve was the first to introduce me to the idea that we shouldn’t be thinking of psychobiological effects in terms of inert placebos and nocebos, but in terms of context, meanings, beliefs and expectations. This resonated perfectly, but I am also intent on strategising to achieve meaningful change, and so I have maintained that it is useful, at this time, to use terms that are familiar to those hearing them.

The second day was highlighted by a presentation on the use of open label placebo, ie: the persistence of the response even when people know they are receiving a placebo. This was presented by Dr Claudia Carvalho, from Portugal, who authored a much publicised recent study on non-deceptive placebo in chronic lower back pain.  This study follows on from a similar study in irritable bowel syndrome but closer examination of both studies reveals that it was the information provided that primarily influenced the outcome even though the focus in publicity was on the placebo. The presenter advised something that was not published. She informed that the instinctive human quest for a ‘cure’ meant that those involved in the study sought to continue their placebo tablets even after the study had concluded! Back to you, Daniel Moerman and Steve Kamper; these studies support the view that it is the ‘meaning’ and knowledge that facilitates the responses but pragmatically, this view alone may not suffice.

Other presenters will not be detailed, but were equally deserving. The relevant research base was scrutinised with strengths, weaknesses and needed future directions highlighted. A linguist expert confirmed the problems and possibilities focussing on language communication. Non-verbal communication was also discussed and even product labelling and perceived trustworthiness can influence health responses. An ethical dilemma that is created by the statistically increased likelihood of complications and side effects induced by a nocebo response when people are pre-informed of these complications, was explored. Importantly, an enlightened public hospital anaesthetist informed that an altered communication approach in post-operative pain can avert long term opioid problems.

Overall, the symposium was excellent and provided information true to its aims. And yet, I remained strangely unsettled by aspects of the experience.

I have discussed in a prior blog my concerns about certain difficulties in educative processes. In my blog on the “Traffic Jam of Pain” I discussed my observation that many conference attendees interpret information selectively to suit preconceptions and refuse to surrender their  cognitive biases.

This concern was reinforced by several audience questions. The most prominent one was a question posed by a physician approaching the topic from a standard musculoskeletal, ’tissue change = pain’, perspective. He stated that what he gained from a presentation was that he had erred in the past by focussing on an evidence based approach (is there any robust evidence in musculoskeletal medicine?), but should have adopted a higher focus on simply ‘selling’  interventions in a more positive light. I don’t think that this is what ‘harnessing’ psychobiological responses is about at all, and found this interpretation disturbing. Better marketing of methods that have no direct benefits has a distinctly dark side. Few interventions are harmless and continuing to focus on ‘fixing’ things has an inherent pain perpetuating effect because it maintains a focus on ‘damage’ as the main cause of pain.

Following on from this, my concern lies with the group that are the placebo ‘non-responders’ after injuries and initial pain events.  This is the group that corresponds numerically with our troublesome chronic pain population. This is the group that is worryingly still growing in number. This is the group of people who have a pain event and are then swallowed by a health industry convinced that selectively observed effects and poor evidence justify the repeated use of pharmaceuticals and interventions. Placebo construct responses are intrinsically context dependent and the context of the ‘non-responders’ keeps violating any meaningfully positive responses. Most of those providing treatments are convinced of the effectiveness of their methods using an observational, flat earth science equivalent approach. Some are like the problematic question-asker described in a previous paragraph and are consciously manipulating placebo construct responses for ‘good’.

I emphasise again that the problem with these methods is that it never empowers patients to recover meaningfully. On the contrary, from a neurobiological perspective it likely has a major ‘catch 22’ role in pain perpetuation by convincing vulnerable people that they have non-adaptable damage that needs ‘fixing’. This type of harnessing of placebos never educates people to understand that it is the context, meanings, beliefs and expectations that need to be re-adapted for the best and safest results to be achieved. In this sense, I completely agree with Daniel and Steve.

In real world situations, people in pain go from one intervention to another, perceiving minimal / partial / temporary benefits from each. Both they and their treating clinicians perceive these responses as appropriately beneficial but the overall trajectory of the problem keeps going in the wrong direction.

There is an abundance of unhelpful contextual inputs generated by a health industry that is incentivised to intervene and disempower. From a neurobiological perspective, there are many reasons as to why re-adaptive processes are sabotaged by imposed context and expectations. This does not just occur via easily recognisable ‘nocebo’ messages; suboptimal interpretation of placebo responses has a similarly unhelpful effect.

I fear that harnessing placebo mechanisms alone is an insufficient message. I propose that comprehensively understanding and prioritising neurobiological mechanisms, which include placebo / nocebo mechanisms is a far better message. Education on such mechanisms with full perspective empowers us all.

Any who have read my prior blogs and various social media posts will recognise my tendency for associating my thoughts with quotes, films, books, song lyrics and similar. The troubling thoughts generated by aspects of this otherwise excellent symposium made me think of one of my favourite Looney Toon cartoon characters, Yosemite Sam –

I suspect that harnessing placebo processes meaningfully will require a different approach. Little did I know when enjoying Yosemite Sam when younger that he would provide such a useful metaphor in the future that would play in my mind repeatedly during a symposium. To those managing pain out there in a neurobiologically deficient context – “When I say whoa, I mean whoa!”