Hyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome

[pattismith]

• 
  
• Published: 30 March 2019

Hyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome

• Masaya Yasui,
• Yuki Menjyo,
• Kyohei Tokizane,
• Akiko Shiozawa,
• Makoto Tsuda,
• Kazuhide Inoue &
• Hiroshi Kiyama

Abstract
Background
Patients diagnosed with chronic fatigue syndrome (CFS) or fibromyalgia experience chronic pain. Concomitantly, the rat model of CFS exhibits microglial activation in the lumbar spinal cord and pain behavior without peripheral tissue damage and/or inflammation. The present study addressed the mechanism underlying the association between pain and chronic stress using this rat model.
Results
The expression of ATF3, a marker of neuronal hyperactivity or injury, was first observed in the lumbar dorsal root ganglion (DRG) neurons 2 days after CS initiation. More than 50% of ATF3-positive neurons simultaneously expressed the proprioceptor markers TrkC or VGluT1, whereas the co-expression rates for TrkA, TrkB, IB4, and CGRP were lower than 20%. Retrograde labeling using fluorogold showed that ATF3-positive proprioceptive DRG neurons mainly projected to the soleus. Substantial microglial accumulation was observed in the medial part of the dorsal horn on the fifth CS day. Microglial accumulation was observed around a subset of motor neurons in the dorsal part of the ventral horn on the sixth CS day. The motor neurons surrounded by microglia were ATF3-positive and mainly projected to the soleus. Electromyographic activity in the soleus was two to three times higher in the CS group than in the control group. These results suggest that chronic proprioceptor activation induces the sequential activation of neurons along the spinal reflex arc, and the neuronal activation further activates microglia along the arc. Proprioceptor suppression by ankle joint immobilization significantly suppressed the accumulation of microglia in the spinal cord, as well as the pain behavior.
Conclusion
Our results indicate that proprioceptor-induced microglial activation may be a key player in the initiation and maintenance of abnormal pain in patients with CFS.

 

[Gemini]

Our results indicate that proprioceptor-induced microglial activation may be a key player in the initiation and maintenance of abnormal pain in patients with CFS.

@pattismith thanks for posting this interesting study & findings.

Hopefully future studies will carry them forward.

 

[SlamDancin]

I think ankle immobilization is key for me as well

 

[anne_likes_red]

I think ankle immobilization is key for me as well

I had some postural evaluation done where it turned out my feet weren't pointing quite where I thought they were lol. Definitely something's amiss with my proprioception. I assumed a deficiency...but perhaps hyperactivation somewhere as some kind of compensation is more accurate?
Twice when I've had brief remission episodes my sense of proprioception has normalised (as best I can tell!) and pain and inflammation reduced to indetectable.

 

[SlamDancin]

I have flat feet and rely way too much on my heels so those have to get lifted and so I have PT prescription orthotics.

 

[junkcrap50]

Also regarding delta waves I came across this recent case study while I was searching for anything showing links between proprioception dysfunction and me/cfs.
http://people.bath.ac.uk/ac886/PDSandMECFS.pdf It's intriguing! Though I don't know what diagnostic criteria their subjects would meet...Oxford I guess?

The lead author is an opthalmologist in Portugal - https://www.orlandoalvesdasilva.org/
In clinical studies over the last 20 - 30 years he seems to have demonstrated the active prism lenses he prescribes as part of his treatment for proprioception dysfunction syndrome* (as described in those "ME/CFS" case studies at Bath) normalised the pattern of delta wave production. I have read elsewhere that PWME produce these slow waves during waking hours instead of during sleep. Gulf war illness sufferers too I think?

View attachment 33568
That's clipped from a recent (June 2019) journal http://pubs.covd.org/VDR/issue5-2/index.html. Dr Alves da Silva's contributed article appears from page 130. You can download it as a pdf for easier reading if you're interested.

Very interesting paper that @anne_likes_red linked to how proprioception disorder cured severe ME/CFS. May be related?

 

[anne_likes_red]

I've been in dialogue with the main author of that paper and I've spent a few months google translating his and his colleagues papers etc. going back to the 1970's. ...And their forebears work from the 1950s and even earlier! Posturology and proprioception is a fascinating subject.

It seems proprioception deficiency syndrome presents similarly to spaceflight sickness with the immune and autonomic effects strikingly like what some PWME experience. So there could be a subset at least helped by this kind of intervention.

Dr da Silva said he thinks 10% of the population in industrialized countries have some extent of proprioception dysfunction.
He is an ophthalmologist so he treats with active prism lenses and he works closely with general postural as well as jaw alignment (dental) professionals to correct the overall deficiency / dysfunction seen in PDS patients.