Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine) Nijs et al.

Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine

Authors include Nijs and Clauw. Published in the Lancet. Full paper here. Includes ‘chronic fatigue syndrome in the text and tables.


Summary

Chronic pain is a leading cause of disability globally and associated with enormous health-care costs.

The discrepancy between the extent of tissue damage and the magnitude of pain, disability, and associated symptoms represents a diagnostic challenge for rheumatology specialists.

Central sensitisation, defined as an amplification of neural signalling within the CNS that elicits pain hypersensitivity, has been investigated as a reason for this discrepancy.

Features of central sensitisation have been documented in various pain conditions common in rheumatology practice, including fibromyalgia, osteoarthritis, rheumatoid arthritis, Ehlers-Danlos syndrome, upper extremity tendinopathies, headache, and spinal pain.
Within individual pain conditions, there is substantial variation among patients in terms of presence and magnitude of central sensitisation, stressing the importance of individual assessment.

Central sensitisation predicts poor treatment outcomes in multiple patient populations.

The available evidence supports various pharmacological and non-pharmacological strategies to reduce central sensitisation and to improve patient outcomes in several conditions commonly seen in rheumatology practice.

These data open up new treatment perspectives, with the possibility for precision pain medicine treatment according to pain phenotyping as a logical next step.

With this view, studies suggest the possibility of matching non-pharmacological approaches, or medications, or both to the central sensitisation pain phenotypes.

 

Hold up. May I ask someone to fill me in on the evidence base for CSS in ME?

Pain doesn't seem to play a central role in most case definitions, and personally I have little problems with it - albeit that'd make some say that I do not fulfill the "myalgic" part of ME. The only citation provided re. ME was this, synthesizing a bunch of pain threshhold tests as evidence that ME is a CSS. If you define CSS to mean just that, anyone with abnormal testing will trivially have it. I question the specificity of this, but I suppose CSS enthusiasts would like to point out that any CSS condition exhibits a manifestation of the same monolithic mechanism, without further proof. It seems like they're fishing for explanations why their preferred treatment options ought to work, rather than figuring out why they don't.

That paper above was also authored by Nijs, which makes me feel like they're taking the "when all you have is a hammer" approach to this line of research. At least in Fibromyalgia, you've got findings implicating a variety neuropeptides in the CSF that are vaguely associated with pain, like substance P, but do these exist in ME as well? Evengard, 1998 found nothing. Measures of muscle fatigability could further clarify the differences. I'm close to someone with Fibromyalgia, and our conditions "share many clinical features" only in the broadest sense. For instance, their flareups don't correspond to all kinds of exertion, but rather emotional stress, food intolerances, and hormonal fluctuations, which make no difference to me.

In particular, I would like an explanation for why the same treatment options that *sometimes* work in Fibromyalgia, practically never work for anyone in ME. If you consider ME and Fibro two phenotypes of the same phenomenon, wouldn't it follow that some of the same treatments targeting the same central pathomechanism would result in similarly reduced symptomatology? Yet, I never heard of any ME patient responding positively to the usual "first-line" Fibromyalgia treatment options of Gabapentinoids, SNRIs, TCAs, and especially exercise, but maybe I'm missing something.

I was going write a rant about precision medicine being a bit of a pipe dream for the near future, and that in the context of "complex conditions" it generally only means one thing, but the main text kind of confirmed it.

They really must have a low bar for what precision even means. ¯\_(ツ)_/¯

 

When "central sensitization" is used in connection with ME/CFS, as Andrew Lloyd seemed to use it in Australia, the concept seems to be taken directly from pain but then approached like arachnophobia or some other phobia--that gradual exposure to increasing exercise will reduce the so-called "sensitization." It's an explanation that is back-engineered into CFS as a way to justify GET since deconditioning is clearly not the problem. So the theory now for why GET "works" is that it is desensitizing the patients.

 

N=1 here.

Pain was one of the first big problems that initially had me booking an appointment with my GP. These days my pain is manageable - so long as I manage my ME well.

Since developing ME I have had a fair bit of dental work done, most of it by my current dentist. He doesn't think I am any more sensitive to pain than anyone else. He's more concerned about the possibility of me being in pain than I am as the adrenaline free local injections he uses for me aren't as strong as the usual stuff and come in smaller vials.

The only comment worthy thing he has noted is that I am very accurate when I tell him where the pain is and what it's like. I can direct him right to the problem. He also says some people are very good at specifying exactly what side of which tooth hurts whereas as others can only say which side the pain is on.

I have also managed to stand on a fire ants nest while wearing flipflops & talking to a neighbour and neither the neighbour nor my husband noticed that I was being stung/bitten. It smarted but nothing registered on my expression and I didn't flinch at all because I'm used to getting the odd stinging and burning sensation that can come out of nowhere and be very strong. I usually ignore it because there's usually nothing there. So I do feel pain but can often just ignore it even when it's at a level where most people would react.

The other thing I will suggest about pain is that in my personal experience, the fitter you are and more muscle tone you have the less some types of injuries or knocks will hurt. If investigating this type of pain it's important to match with sedentary healthy controls with similar muscle tone.

 

More info here: https://www.s4me.info/threads/central-sensitization-a-matter-of-concern.5346/

 

The big question that the authors don't answer is: how do we know that central sensitization is happening or not?

They define central sensitization as "amplification of neural signalling within the CNS that elicits pain hypersensitivity" but as far as I can see one can't really test or measure whether neural signalling is amplified in the conditions described.

They only have indirect indications such as reduced pain thresholds or temporal summation. So if those are the phenomena we can see and measure why not just call them that? Why add a speculative term like central sensitization which suggests an explanation which at present remains highly uncertain?

They also mention the Central sensitization inventory (CSI) but this questionnaires only asks about some common symptoms, from unrefreshed sleep, diarrhoea, difficulty concentrating, low energy, polyuria etc. I could have just as well have named it the 'neuroinflammation questionnaire' or the 'adrenal fatigue questionnaire', that doesn't mean it is able to pick up neuroinflammation or problems glands.

 

Could someone please tell me if central sensitisation is a proven phenomenon or is it just an idea?

 

Just an idea from people who would like to make money out of desperate people...

 

I want to ask a practical question. Do doctors in the UK (specifically England) treat new cases of chronic pain? Or old cases of chronic pain that are getting substantially worse for no obvious reason? Or do they just give out a mental health diagnosis and refer patients to IAPT, CBT and GET and suggest anti-depressants? In effect, I'm asking is there any point in me ever seeing a doctor again if the condition I want to discuss is an old one and is not visible? Having bought a copy of my GP records a few years ago I have proof of some serious health problems going back to the 1970s. But will I just get told that they can't be causing pain any more and it's all in my head?

 

I won't bother then. I was seen by a pain clinic a few years ago and it was a complete waste of time. They were only prepared to suggest treatments that GPs had already tried which had already failed to make a dent.

 

I've lived in my current area for about 35 years. If I haven't found something good in all that time I'm not expecting to find it now. My local hospital, for example, has gaslighted me for decades. I had a truly astonishing appointment there (in a bad way) in 2019 which was the last straw that finally made me lose all hope of ever being taken seriously about anything unless it is actually visible. It followed an equally bad appointment in a different hospital the year before. All the successful (although still limited) treatment I've had (while living where I currently do) has been in a neighbouring hospital, but I only get referred there for things my local hospital doesn't do.

There is only so much being shit on from a great height that anyone can be expected to cope with, and I've been dealing with it now for nearly 50 years. I've just had enough.

 

I'm not even sure there is such a thing as central sensitisation. Period. Its a collection of phenomena defined by what they aren't, not what they are. They aren't pain with a single known peripheral source (e.g., local inflammation, broken bone, etc). But probably only a small fraction of the pain people experience regularly fits this narrow definition. I smell yet another form of god-of-the-gaps reasoning: if we can't identify the precise mechanism responsible for your pain, then its coming from your thoughts, feelings and behaviours. They may say "brain", but that's just sophistry, to make the concept more respectable. They're not suggesting we have neurological problems or need neurosurgical solutions. What they actually mean is just our thoughts, feelings or learned behaviours.

FFS, leave the brain out of it and speak plainly.

Okay, so increased pain thresholds that are non-specific as to region suggest something a little different from pain whose source is a specific set of nociceptors (CNS pain receptors), but there are still a thousand of other sources of pain, some not all that central at all. Even temporal summation (the phenomenon whereby repeated pain stimulation to the same site can heighten the pain response over short periods) is pretty peripheral, it certainly doesn't involve your thoughts, feelings and behaviours,

I wonder if the people touting this stuff have ever had a backache during a nasty 'flu? There's one right there. Its probably not a direct effect of stimulation of a CNS nociceptor, but its not that central either. Do we think that's caused by thoughts, feelings or behaviours? Of course not!

So I do wish they would stop using phenomena like that to support the idea that you can something train yourself out of feeling pain.

 

I read most of the article. The salient point (especially seen in the literature review) is to be able to identify those patients for example who go on to have knee replacements who will have worse pain results post surgery (after the rehab period) than pre-surgery. These patients have been identified as persons with moderate-severe fibromyalgia. This concern is with identifying central sensitization, which is in the context of pain.

Throwing ME/CFS in the mix is unfortunate. There can be overlap with fibromyalgia and other conditions, but daily pain isn't universal in ME (right?).

There is, therefore, a need for identifying those patients who meet the criteria (TBD) for central sensitization in the context of pain in many speciaities of medicine and surgery in order to have better outcomes.

The concept of central sensitization, as I understand it, is only used for chronic pain that worsens in time.

 

You are kind, @shak8.

But look at some of the things they say:

So, make the pain in the periphery go away and so too will the "central sensitization"? But if the source of the pain is the periphery then surely this isn't "central sensitisation", in the sense that the term is normally used? I don't think anyone genuinely believes that the subjective pain experience is non-summative - surely we would all expect to be in more pain overall from breaking every limb, than we would from breaking just one. But this is not what is usually implied by "central sensitisation", which is some sort of top-down enhancement of the pain experience.

Here is the problem again:

There seems to be a lot of slipping and sliding about what "central sensitisation" really is, sometimes the term is used to refer to an empirical phenomenon (temporal summation, or lowered pain thresholds to pain outside of the injured area), sometimes to high scores self-reported measures of pain and other somatic symptoms, and these authors treat all these measures as interchangeable, and measuring some single underlying phenomenon.

The neuroimaging data they refer to doesn't imply central sensitisation, because pain of any sort will be detectable as changes in neural activity, it does not demonstrate that this is the origin in terms of cause.

And don't get me started on pain neuroscience education.

 

Please? I am interested.