MicroRNAs as biomarkers of pain intensity in patients with chronic fatigue syndrome. Al-Rawaf (2019)

John Mac

John Mac

Senior Member (Voting Rights)
Abstract
BACKGROUND:
Numerous experimental models have shown that microRNAs play an important role in regulating pain-processing in clinical pain disorders.
In this study, we evaluated a set of micro-RNAs as diagnostic biomarkers of pain intensity in adolescents with chronic fatigue syndrome (CFS).
We then correlated the expression of these microRNAs with the levels of inflammatory markers and pain-related comorbidities in adolescents with CSF and healthy controls (HCs).

METHODS:
A total of 150 adolescents, aged 12-18 years, participated in this study between April 2016 and April 2017.
The participants were classified into two groups: adolescents with CFS (n=100) and HCs (n=50).
RT-PCR was used to evaluate the expression of miR-558, miR-146a, miR-150, miR-124, and miR-143.
Immunoassay analysis was used to assess the levels of immune inflammatory markers IL-6, TNF-α, and COX-2.

RESULTS:
Adolescents with CFS showed significantly higher pain thresholds than comparable non-fatigued HCs.

Also, enjoy of life and relation to others as the life domains, showed lower pain interference in CFS patients.

Differential expression of miR-558, miR-146a, miR-150, miR-124, and miR-143 was significantly down regulated and notably interfered with pain intensity and frequency in patients with CFS.

Also, the expression of these miRNAs was significantly correlated with that of IL-6, TNF-α, and COX-2, which have been shown to mediate pain intensity in patients with CFS.

Girls with CSF showed significantly decreased expression levels of these miRNAs compared with the levels of boys with CSF.

Girls with CSF also showed increased expression of inflammatory pain-related markers IL-6, TNF-α, and COX-2, compared with the levels of boys with CSF

CONCLUSIONS: The intensity and consequences of pain were influenced by differential expression of miR-558, miR-146a, miR-150, miR-124, and miR-143, which was directly, associated with higher expression of immune inflammatory related genes TNFα, IL-6, and COX-2 in adolescences with CFS.
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https://www.ncbi.nlm.nih.gov/pubmed/31282597

https://onlinelibrary.wiley.com/doi/abs/10.1111/papr.12817?af=R&
 
I'm having some trouble understanding bits of this. (no surprise there)

I get that they found that the adolescents with CFS had higher pain intensity, lower microRNA and higher inflammatory markers than the healthy controls, and that this same pattern of highs and lows is found in adults with other pain conditions. Have I got that right?

But what does this bit of the abstract mean?

Adolescents with CFS showed significantly higher pain thresholds than comparable non-fatigued HCs.

Also, enjoy of life and relation to others as the life domains, showed lower pain interference in CFS patients.
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To my lay person's mind, that says CFS patients can take more pain stimulus before they feel the pain, and enjoy life more despite their pain. Surely that can't be right.

Here's the relevant bit from the results section:
Functional interference and pain severity scores in adolescences with CFS and HCs are shown in Table 3. The pain severity scores (18.0; p<0.001) and pain interference scores (28.0; p<0.001) were higher in adolescents with CFS than in HCs. Pain severity significantly interfered with functionality and general activity, school attendance, walking, and mood of patients with CFS (Table 3). In both patients with CFS and HCs, the ability to enjoy life and relation to others were the parameters least influenced by pain. Lower pain intensity and functional interference in non -fatigued normal subjects; significantly reflect the large variation in the normal population.
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So if we pick apart that part of the abstract, we have:
Adolescents with CFS showed significantly higher pain thresholds than comparable non-fatigued HCs.
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That should read: Adolescents with CFS showed significantly higher pain severity than comparable non-fatigued HC's

Also, enjoy of life and relation to others as the life domains, showed lower pain interference in CFS patients
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The comparison is not with healthy controls as the abstract seems to imply, but with the effect of pain on other aspects of daily life in CFS patients.
So perhaps it should read:
Also, all aspects of life domains are worse in CFS patients than HC's but the ability to enjoy life and relations with others are the least affected life domains.
 
Adolescents with CFS showed significantly higher pain thresholds than comparable non-fatigued HCs
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Nevermind the "non-fatigued" part that makes the whole thing dubious, is this phrased correctly, meaning CFS patients have more pain tolerance? It's a bit ambiguous as it could apply both ways.

I'm not really sure how this could be interpreted in an objective way, though. Being in pain all the time means a significant skewing of the pain scale. What is a 5 to a healthy person may be a 3 for us since much greater pain levels than normal are basically typical. But likely only on pain that is part of the disease and familiar. And just with the example of spicy food preferences, the possible range of pain sensitivity is huge.

Basically all this can report is relative pain, not absolute. Without a way to standardize it becomes impossible to interpret anything of significance. It's like comparing whether someone in London thinks X amount of rain is a lot and comparing that to someone who lives in the Arizona desert. The same question would have different answers and would follow if the two people moved, their own scale would adapt.

Without an objective way to measure pain, this is the fatal flaw in any evaluation of pain. Questionnaire-based research is too weak to be of use.
 
It's garbled but if it means what I think it means, that's interesting. If patients have a higher pain tolerance, it suggests they're not hypersensitive to pain.
 
I would agree
adambeyoncelowe said:
It's garbled but if it means what I think it means, that's interesting. If patients have a higher pain tolerance, it suggests they're not hypersensitive to pain.
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I would agree re pain tolerance.
My daughter finds it difficult to compare pain / " meh face" scores on a diary app she has as her pain tolerance has changed over time, probably as the nature and degree of pain has changed. People become accustomed to a background pain level.

The sheer resilience of those with ME is amazing.
 
adambeyoncelowe said:
It's garbled but if it means what I think it means, that's interesting. If patients have a higher pain tolerance, it suggests they're not hypersensitive to pain.
Click to expand...

But I couldn't see anywhere any mention that they tested pain threshold or pain tolerance. All they did was get them to fill in questionnaires on pain intensity.

https://www.sciencedirect.com/topics/medicine-and-dentistry/pain-threshold
Ronald Kanner MD, in Pain Management Secrets (Third Edition), 2009

7 What is the difference between pain threshold and pain tolerance?
Pain threshold refers to the lowest intensity at which a given stimulus is perceived as painful; it is relatively constant across subjects for a given stimulus. For example, most subjects will define a thermal stimulus as painful when it reaches about 50° C. Similarly, barring disease states, mechanical pressure produces pain at approximately the same amount of pressure across subjects. Pain threshold as it relates to sensitivity to pressure is measured with an algometer.

Pain tolerance, on the other hand, is the greatest level of pain that a subject is prepared to endure. Tolerance varies much more widely across subjects and depends on prescribed medications. Clinically, pain tolerance is of much more importance than pain threshold. (More detailed discussions of threshold and tolerance are found in Chapter 6, Pain Measurement.)
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