Hyper-connectivity between the left motor cortex and prefrontal cortex is associated with the severity of dysfunction ... in FM, 2022, Oliveira Franco

Full title: Hyper-connectivity between the left motor cortex and prefrontal cortex is associated with the severity of dysfunction of the descending pain modulatory system in fibromyalgia

Abstract
Introduction
The association between descending pain modulatory system (DPMS) dysfunction and fibromyalgia has been previously described, but more studies are required on its relationship with aberrant functional connectivity (FC) between the motor and prefrontal cortices.

Objectives
The objective of this cross-sectional observational study was to compare the intra- and interhemispheric FC between the bilateral motor and prefrontal cortices in women with fibromyalgia, comparing responders and nonresponders to the conditioned pain modulation (CPM) test.

Methods
A cross-sectional sample of 37 women (23 responders and 14 nonresponders to the CPM test) with fibromyalgia diagnosed according to the American College of Rheumatology criteria underwent a standardized clinical assessment and an FC analysis using functional near-infrared spectroscopy. DPMS function was inferred through responses to the CPM test, which were induced by hand immersion in cold water (0–1°C). A multivariate analysis of covariance for main effects between responders and nonresponders was conducted using the diagnosis of multiple psychiatric disorders and the use of opioid and nonopioid analgesics as covariates. In addition, we analyzed the interaction between the CPM test response and the presence of multiple psychiatric diagnoses.

Results
Nonresponders showed increased FC between the left motor cortex (lMC) and the left prefrontal cortex (lPFC) (t = −2.476, p = 0.01) and right prefrontal cortex (rPFC) (t = −2.363, p = 0.02), even when both were considered as covariates in the regression analysis (lMC–lPFC: β = −0.127, t = −2.425, p = 0.021; lMC–rPFC: β = −0.122, t = −2.222, p = 0.033). Regarding main effects, a significant difference was only observed for lMC–lPFC (p = 0.035). A significant interaction was observed between the psychiatric disorders and nonresponse to the CPM test in lMC−lPFC (β = −0.222, t = −2.275, p = 0.03) and lMC−rPFC (β = −0.211, t = −2.2, p = 0.035). Additionally, a significant interaction was observed between the CPM test and FC in these two region-of-interest combinations, despite the psychiatric diagnoses (lMC−lPFC: β = −0.516, t = −2.447, p = 0.02; lMC−rPFC: β = −0.582, t = −2.805, p = 0.008).

Conclusions
Higher FC between the lMC and the bilateral PFC may be a neural marker of DPMS dysfunction in women with fibromyalgia, although its interplay with psychiatric diagnoses also seems to influence this association.

Open access, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247629

 

OK I'm only a tiny way through this and there is a lot to get up to speed with in here.

So the test (Conditioned Pain Modulation Test - CPM) they used to identify responders vs non-responders was to have thermode on the left forearm (all are right handed) which heats up to 52 degrees and back down to find out what represents 'pain level 6' (self-report). Then put the individuals right hand in cold water for 5mins and repeat the thermode to get a new number that equates to 6 on the pain scale.

Their theory is that responders are those who get a 'negative score' (ie the second number is higher) apparently because 'pain detracts from pain' so having a freezing hand means they 'withstand' more thermode on the other arm at the same time. Those who basically experienced the same or more pain from the thermode when their other hand is also being tortured were 'non-responders'.

This feels 'leading' terminology to categorise in this way - surely you wouldn't suggest to someone that they alleviate their pain somewhere by hurting somewhere else and call it 'curing pain'? Or are they really convincing themselves of that in this subject area?

I'm intrigued what what this demonstrates as a methodology as there is surely more involved than 'experienced pain' given the cognitive task of telling people to 'yelp when it gets to 6 on the pain scale'? I might find it hard to reply to a question with sensible words full-stop if my hand had been in ice cold water for 5mins.

We have no controls either with no illness or a different one (is fibro consistently sensitive to cold water or could this be an issue in itself as they haven't mentioned Reynaulds specifically as an exclusion in recruitment).

So who are/what are their 'responders' vs 'non-responders' in factual assessment - what does this difference between people mean at all scientifically and precisely? Because it seems these are the 2 they are looking for differences between as if it means something for fibromyalgia?

I don't get how this is a study of fibro at all without them having controls, or giving us numbers of responders vs non-responders. It seems to just be post-hoc saying 'in people with this condition some reacted, one-off, like this, and others like that'. In a condition that varies day by day, with no confirmation that reactions like 'this' are somehow better than 'that'. Or discussion of it

I expected to find more discussing this somewhere in the paper (discussion or conclusion or intro/chosen method) but found the following in the intro:
"Previous research demonstrated that in FM, the spectrum of disability and symptom severity is proportional to the dysfunction of the descending pain modulatory system (DPMS) [20]. Additionally, studies have presented resting-state FC abnormalities across the cortical areas related to top-down modulation of DPMS [21, 22]. The function of DPMS may be assessed by the conditioned pain modulation test (CPM test) [23]. When a subgroup of patients with FM is assessed using the CPM test, they consistently present ineffective endogenous pain modulation [24–29]."

That isn't a lot of references given the assertive language? I haven't looked them up yet, to see how of quality they are..

Happy for someone to correct me in saying the literature itself is indeed 'more decided' on these assertions and there is a strong body meaning this aspect is 'pretty well confirmed'?

In its absence I'm failing to see what they have achieved/would have achieved by their methodology - including when they proposed it?