The genetic architecture of fibromyalgia across 2.5 million individuals, 2025, Kerrebijnet al.

[Jonathan Edwards]

The issue is that while your definition of the term here is reasonable and fits with theories of ME/CFS we have been discussing, the concept of 'central sensitisation' is intrinsically bound up with BPS psychobabble about people misinterpreting normal sensations and having false illness beliefs.

It is for the BPS people but for some pain researchers at least (like Maria Fitzgerald) it is just what it says and very "biological".

 

[Spartacus]

"One particularly notable hit was rs2734833, an intronic variant in DRD2, a locus with pervasive psychiatric and sleep associations. DRD2 encodes the dopamine D2 receptor, which influences motivation and cognition and is the primary target of most antipsychotic drugs. In addition, DRD2 was one of the first loci discovered to modulate sleep duration. The variant lies ~150 kilobases downstream of NCAM1, the fourth-nearest gene, which encodes a cell surface receptor (also known as CD56) with both nervous and immune roles. In the nervous system, it regulates neural cell adhesion, neuronal migration, neurite outgrowth, axon guidance, and synaptic plasticity, and plays a role in memory. In the immune system, CD56 is the primary marker for natural killer (NK) cells and distinguishes their two main subtypes. It helps NK cells attach to target cells and trigger the release of cytotoxic granules that kill target cells."

I am not a scientist or medical professional, so most of this stuff goes way over my head, but I thought this seemed interesting. All the women in my family on my father's side, going back 3 generations, have had fibromyalgia diagnosed or had symptoms but before fibromyalgia was formally recognised. Several of the men on that side, in the last 3 generations have had bipolar. Would these findings suggest that the two conditions could possibly be genetically related? All have had severe insomnia.

 

[Jonathan Edwards]

Another issue is that fibromyalgia is usually not about heightened pain sensitivity when there is peripheral input. It's about constant widespread pain even without any peripheral input. So rather than just have an increased response to pain stimuli when these arise, patients seem to have the pain switch constantly turned on.

So central sensitisation might not be the best term to describe this.

Central sensitisation isn't necessarily intended to describe the whole clinical picture but from what I have heard from people like Fitzgerald it includes things like touch or proprioception signals being routed to pain pathways. Since we have peripheral signals coming in the whole time just from posture this might explain pain without any apparently relevant peripheral input.

She talked about models where microglial activation persists and related that to cross-talk in inputs if I remember rightly.

 

[shak8]

Another issue is that fibromyalgia is usually not about heightened pain sensitivity when there is peripheral input. It's about constant widespread pain even without any peripheral input. So rather than just have an increased response to pain stimuli when these arise, patients seem to have the pain switch constantly turned on.

So central sensitisation might not be the best term to describe this.

There is also impairment of the descending pathway of pain modulation in FM that contributes to pain load.

Brain signatures of nociplastic pain: Fibromyalgia Index and descending modulation at population level - PubMed

Nociplastic pain is defined by altered nociceptive processing in the absence of clear peripheral damage or somatosensory lesions. The Fibromyalgia Index (FMI), derived from the 2016 diagnostic criteria, is increasingly used as a marker of nociplastic pain severity in clinical studies, yet its...

pubmed.ncbi.nlm.nih.gov