Chronic pain is associated with a brain aging biomarker

Chronic pain is associated with a brain aging biomarker in community-dwelling older adults: PAINPAINMay 2019 – Research Paper

This “finding” doesn’t surprise me one bit; my mental faculties have long been deteriorating faster than others in my cohort.

Chronic pain is associated with brain atrophy with limited evidence on its impact in the older adult’s brain.

We aimed to determine the associations between chronic pain and a brain aging biomarker in persons aged 60 to 83 years old

Individuals with chronic pain (n = 33) had “older” brains for their age compared with those without.   

Greater average worst pain intensity was associated with an “older” brain

Among participants with chronic pain, those who reported having pain treatments during the past 3 months had “younger” brains compared with those who did not.

An “older” brain was significantly associated with

  • decreased vibratory and thermal detection,
  • deficient endogenous pain inhibition
  • lower positive affect,
  • a less agreeable and less emotionally stable personality.

That’s evidence of something I’ve long suspected: chronic pain eventually results in brain damage, the kind that makes us distracted, irritable, depressed, and anxious – at least that what seems to have happened to me.

Our findings suggest that chronic pain is associated with added “age-like” brain atrophy in relatively healthy, community-dwelling older individuals

A brain aging biomarker may help identify people with chronic pain at a greater risk of functional decline and poorer health outcomes.

These age-like effects of chronic pain are in addition to “normal” aging, which might explain why I feel like I’m aging in fast-forward.

1. Introduction

More than 1.5 billion people worldwide experience chronic pain, and more Americans are affected by chronic pain than by diabetes, heart disease, and cancer combined.

In particular, epidemiological evidence suggests an age-related increase in pain prevalence with back and knee pain as the most commonly reported pain in those older than 65 years.

Chronic pain in older individuals is a growing public health problem because effective treatments are lacking, and pain detrimentally impacts physical and cognitive function, ultimately decreasing quality of life and overall well-being.

Pain is associated with both direct (ie, the experience of pain) and indirect effects on the brain

Neuroimaging studies have established the prominent role of the brain in pain perception and modulation and in the integration of sensory, motor, emotional, and cognitive components that give rise to the complex, individualized pain experience.

Although most chronic pain conditions are associated with changes to brain structure and function, these structures are similarly impacted by normal and pathological chronological aging processes.

Indeed, chronological aging has been associated with both global and spatially localized changes to brain structure and function, which may be very similar to brain changes reported in chronic pain states.

In addition, several preliminary investigations in older adults with and without low back pain (n = 8/group) suggest that chronic pain may negatively impact the brain above and beyond age-related effects (ie, accelerated brain aging)

Using machine-learning analysis of structural neuroimaging data, chronological age can be accurately predicted in healthy individuals.

Using this method, older predicted brain age (as compared with chronological age) has been reported in

  • Alzheimer disease,
  • mild cognitive impairment,
  • HIV,
  • schizophrenia, and
  • after traumatic brain injury.

Furthermore, recent work found that having an older predicted brain age was associated with

  • weaker grip strength,
  • poorer lung function,
  • slower walking speed,
  • lower fluid intelligence,
  • higher allostatic load, and
  • increased overall mortality risk measured prospectively

Consistent with previous work, we estimated a brain-predicted age difference (brain-PAD, calculated as brain-predicted age minus chronological age) using structural neuroimaging (T1-weighted magnetic resonance imaging [MRI]) processed through an established analysis pipeline

The primary hypothesis of the present study was that older adults reporting chronic pain will have a greater brain-PAD (ie, older brain, accelerated brain aging) compared with older adults who did not report chronic pain during the past 3 months.

2. Methods

A clinically relevant, neuroimaging-derived aging biomarker, previously predictive of greater mortality risk during aging, is similarly associated with the complex experience of pain in older individuals.

2.3.5. Conditioned pain modulation procedure

A subset of participants completed a conditioned pain modulation (CPM) paradigm as recommended by Yarnitsky et al.

For the test stimulus, heat was applied to the thenar eminence increasing at a rate of 1°C/second and was discontinued by the subject at pain-40 (pain level of 40/100).

  • The temperature required to produce pain-40 was recorded
  • A pain inhibition score was calculated

2.5. Brain-predicted age biomarker

The brain aging biomarker used here was derived using a previously established “brain-age” framework.

This involved training a machine-learning model to accurately predict chronological age from neuroimaging data in a training cohort composed of 2646 healthy individuals

So brain age is being determined solely by physical brain imaging qualities, avoiding any reliance on patients’ subjective experiences.

This is significant because almost all aspects of pain can only be subjectively self-reported, while the computations used to determine brain age only involve objective physical brain markers.

The individual participants’ chronological age was then subtracted from this brain-predicted age value to generate a brain-predicted age difference (brain-PAD) score, which was used for further analysis.


3.1. Demographics

Forty-seven older adults ranging in age from 60 to 83 years (mean age = 70.9 ± 6.0; 74.5% female) participated in our study.

3.2. Brain-predicted age difference and presence of pain

There was a significant difference in brain-PAD between older adults who reported chronic pain (1.5 ± 1.6) vs those who did not (−4.0 ± 1.9; F [1,41] = 4.9; P = 0.033; partial eta squared = 0.11, ANCOVA; Fig. 3), which was our main proposed study hypothesis.

3.3. Brain-predicted age difference and worst pain characteristicsWorst pain location within the participants who experienced pain (n = 33) is depicted in Figure 4.

Brain-PAD significantly correlated with average intensity of the worst pain (r = 0.464; P = 0.011; corrected P = 0.033).

3.4. Brain-predicted age difference and psychological function

Spearman correlations were used to determine associations between brain-PAD and psychological variables

No significant associations between brain-PAD and the psychological variables emerged across all participants

3.5. Brain-predicted age difference and quantitative sensory testingGreater vibratory detection thresholds were significantly associated with greater brain-PAD (ie, older brain)

Similarly, greater thermal detection thresholds were also significantly associated with greater brain-PAD (ie, older brain)

3.6. Brain-predicted age difference and conditioned pain modulation

The paper continues with many more categories:

Chronic pain is associated with a brain aging biomarker

6 thoughts on “Chronic pain is associated with a brain aging biomarker

  1. canarensis

    “my mental faculties have long been deteriorating faster than others in my cohort.”
    I feel the same, but I gotta say, considering the mental faculties I’ve observed in you over the last…what, nearly a year now since I found this blog & met you? I can’t decide which seems scarier…that your cohort is considerably ahead of you, or that your faculties were considerably sharper & more acute than they are now. I think the term “awesome” in its rather archaic meaning applies –as in, I’m awed. I encountered quite a few truly impressive minds in my meanderings through science and academe (including other disciplines, such as math & lit), and still think you measure up just fine (apologies if I sound sycophantic, I’m just truthing here).

    OTOH, the idea that you –and me, for whatever brain I once had– could be considerably better off if we’d been able to access adequate & effective levels of treatments all along makes me wonder where we’d be if undertreated pain hadn’t gone through our brain cells like Sherman through Atlanta…what human capital has been wasted and wiped out by hysterical idiocy? Even if I was an idiot all along, it’s rather like wondering how many Einsteins and Schweitzers and such have been snuffed out by refusal to address poverty and starvation around the world and in this country. But heaven forbid we should think of putting some sort of brakes on corporations and CEOs from wallowing in their billions. After all, corporations are people too, now. God help this country…it sure doesn’t seem to be willing or able –or to have the brains– to help itself.

    Liked by 2 people

    1. Zyp Czyk Post author

      I’m still trying to figure out how to respond to your effusive praise: I’m deeply flattered, especially since I consider you very smart and competent, but it also challenges me to do more. If I’m anywhere near as smart as you think, I should be contributing more – but how, what, and to whom I don’t know.

      I should also point out that it’s easy to criticize and disparage the ideas of others, and much harder to present ideas or structure arguments of my own. But to practice my own writing, I’m pushing myself to comment more on what I post, putting more of my own words out there.

      Instead of posting excerpts with a few comments, I’d like to post comments with a few excerpts and eventually, I may write enough for an article of my own again. That’s much harder and takes more time & energy, but your praise certainly gives me a big push.

      I hope you can see how you’ve inspired me – thank you so much!


      Liked by 2 people

      1. canarensis

        Oh my, I definitely didn’t want to make you feel like I was complimenting you while simultaneously cranking up the guilt! I admire your quality of thought & analysis, but in no way think more quantity is expected or required! (heck, look at how long it took Darwin to publish “On the Origin of Species,” & no one could accuse him of being a dimbulb). I’m already impressed (& I know I’m not alone; I read other’s comments, too) with the amount of work you’ve already put in; this is an amazing source of info! I also didn’t mean to embarrass you; I meant it as grateful support & respect. I strongly support your desire to write as you want, as well as when/how much you’re up to. Seriously, I’m the last person in the world to have any thoughts about pace or quantity of output! (the 2 books that got vanished when my last computer croaked were in process for…well, the first one got started before Mom passed away in ’97, tho the short story that was the genesis of it got published just a few months before, so she got to see it).

        For me, at least, the more pressured I feel to produce, the less I can. So please try not to feel pressured; I meant to provide positive feedback, not stress. There’s too much of that floating around us already, I don’t want to add to it!

        Liked by 1 person

  2. peter jasz

    (RE: ” ..Chronic pain is associated with a brain aging biomarker ” )

    As would regular hormone testing/moitoring for Intractable Pain: See Pain Specilaist/Expert Dr. Forest Tennant’s many insights into/for intractable pain patients …

    To think that, in the 2020-th year AD, the medical community is still “grappling” with the human nervous system while simultaneously noticing, tracking, locating and then photographing a space-rock (in surprising detail) -billions-of-miles from Earth, and yet “they” (medical research) doesn’t know what sits a few inches below our own skin (our CNS) ? Think about it, It’s laughable and deeply naive if it’s believe d that “they” don’t know PRECISELY where the problems lay, -how to diagnose, treat -and overcome.

    BUT, that;s neither very profitable -nor self-sustaining: the goal/objective of many disturbingly wealthy/influential institutions is to ENSURE growth. Specifically, create a need (the greater the better) and a steady-over-flow of desperate (pain) sufferer’s clambering, begging for desperate help/ relief is what males this ‘Institution’ so damning..
    This, my friends, sets the wheels in motion; a ‘billions-of-dollar-a-year’ enterprise that would make their greedy forefathers blush with envy: A fountain of wealth upon which Medicine, (Western) pharmaceuticals, governments and the filthy, unrelenting desire for more/more money from these insatiable, blood-thirsty sociopathic enterprises draw upon. A uninterrupted fountain/flow of wealth and power -and the deadly, unavoidable corruption that surfaces.

    In the end, one never knows; for the weak, may very well inherit the Earth.

    Imagine that.




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