ASICs required for immediate exercise-induced muscle pain

[pattismith]

ASICs are required for immediate exercise-induced muscle pain and are downregulated in sensory neurons by exercise training

Tahsin Khataei
,
Anne Marie S. Harding
,
Mahyar Janahmadi
,
Maram El-Geneidy

23 JUN 2020

Abstract
Exercise training is an effective therapy for many pain-related conditions, and trained athletes have lower pain perception compared with unconditioned people.

Some painful conditions, including strenuous exercise, are associated with elevated levels of protons, metabolites, and inflammatory factors, which may activate receptors and/or ion channels, including acid-sensing ion channels (ASICs), on nociceptive sensory neurons.

We hypothesized that ASICs are required for immediate exercise-induced muscle pain (IEIP) and that exercise training diminishes IEIP by modulating ASICs within muscle afferents.

We found high-intensity interval training (HIIT) reduced IEIP in C57BL/6 mice and diminished ASIC mRNA levels in lumber dorsal root ganglia, and this downregulation of ASICs correlated with improved exercise capacity.

Additionally, we found that ASIC3 −/− mice did not develop IEIP; however, the exercise capacity of ASIC3 −/− was similar to wild-type mice.

These results suggest that ASICs are required for IEIP and that diminishment of IEIP after exercise training correlates with downregulation of ASICs in sensory neurons.

NEW & NOTEWORTHY Exercise performance can be limited by the sensations of muscle fatigue and pain transmitted by muscle afferents. It has been proposed that exercise training abrogates these negative feedback signals. We found that acid-sensing ion channels (ASICs) are required for immediate exercise-induced muscle pain (IEIP). Moreover, exercise training prevented IEIP and was correlated with downregulation of ASICs in sensory neurons.

 

[Wishful]

This might apply to some PWME, but I'm guessing that the level of exercise training required for a noticeable effect will be beyond what most PWME can tolerate. It's possible that it's a non-linear function, and those with the lowest fitness could see the most improvements from small increases in exercise. Anyone for experimentation?

A safer way to test this is from existing observations. Has anyone here noticed a significant reduction in muscle pain from increases in exercise?

 

[pattismith]

This might apply to some PWME, but I'm guessing that the level of exercise training required for a noticeable effect will be beyond what most PWME can tolerate. It's possible that it's a non-linear function, and those with the lowest fitness could see the most improvements from small increases in exercise. Anyone for experimentation?

A safer way to test this is from existing observations. Has anyone here noticed a significant reduction in muscle pain from increases in exercise?

yes I think that some of us have hyperexcitable ASIC 3 in muscles' small nerve fibers (C and Adelta), which would explain the pain during exercise and also the pain after the exercise lasting for days.
This last one is called Delayed onset muscle soreness (DOMS) and the link with ASIC 3 and small fibers was shown in this study ;

https://forums.phoenixrising.me/thr...ensitivity-after-exercise.80584/#post-2283295

 

[wabi-sabi]

Has anyone here noticed a significant reduction in muscle pain from increases in exercise?

No- the more I exercise the more I hurt. Pain goes away with enough rest and time on the heating pad. In fact, my pain pretty much only comes on in response to exercise- if you can call getting myself to the mailbox exercise.

 

[pattismith]

No- the more I exercise the more I hurt. Pain goes away with enough rest and time on the heating pad. In fact, my pain pretty much only comes on in response to exercise- if you can call getting myself to the mailbox exercise.

the pain reduction with training is suppose to work for healthy people, not for CFS/ME.

It doesn't work for me either.

The muscle pain with exercise comes from hyper reactivity of the small berve fibers (C and A delta) and ASIC 3 receptors excitation.

This mean that our muscle pain is a small nerve fiber dysfunction, with probable hyper reactivity of ASIC 3.

 

[Pyrrhus]

Here's some information from Wikipedia about Acute Muscle Soreness (AMS):

Acute muscle soreness (AMS) is the pain felt in muscles during and immediately, up to 24 hours, after strenuous physical exercise. The pain appears within a minute of contracting the muscle and it will disappear within two or three minutes or up to several hours after relaxing it.

The following causes have been proposed for acute muscle soreness:

• Accumulation of chemical end products of exercise in muscle cells such as lactic acid and H+
• Muscle fatigue (the muscle tires and cannot contract any more)

Source: https://en.wikipedia.org/wiki/Acute_muscle_soreness


From other papers I've read, the mechanism behind acute muscle soreness may actually be a mix of:

1. H+ leaking from the stressed muscle mitochondria activate the acid sensors (ASICs) on neighboring cells.
2. ATP leaking from the stressed muscle cells activate the purine sensors (P2X) on neighboring cells.

Despite a prior misconception, the contribution from lactic acid appears to only be temporary, as lactic acid is quickly removed from muscle tissue and carried in the blood to the liver, where it is converted to glucose and released back into the blood in a matter of minutes.

 

[Pyrrhus]

Related discussion about a different type of exercise-induced muscle soreness that appears a day or two after exercise:

DOMS (Delayed-Onset Muscle Soreness) is Neural Microdamage Rather Than Muscle Damage
https://forums.phoenixrising.me/thr...-microdamage-rather-than-muscle-damage.82857/

 

[Quest11]

This might apply to some PWME, but I'm guessing that the level of exercise training required for a noticeable effect will be beyond what most PWME can tolerate. It's possible that it's a non-linear function, and those with the lowest fitness could see the most improvements from small increases in exercise. Anyone for experimentation?

A safer way to test this is from existing observations. Has anyone here noticed a significant reduction in muscle pain from increases in exercise?

I’ve recently started body weight exercise again after a very long hiatus. Started with something I felt would be unlikely to cause PEM and not too much pain. I think it was like 10 push ups x3 sets a couple times a week. That was a few months ago. I’m now up to a full body work out 4x a week. My initially base line exercise would be a breeze right now. This is the longest I’ve been able to do resistance exercise consistently without having to stop in 10 years. My previous attempt was 3 years ago and I last a maybe 6 weeks. I think the big difference was that I started with something relatively easy and built up extremely slowly that the workload is never excessive and eventually my muscle strengthen enough for it to become easy. I tried ramping it up a few weeks ago and it caused a crash for half a week.

 

[Wishful]

I had to drive to town; simple, low-exertion task. Unfortunately, we had extremely heavy rains recently, resulting in flooding, including a section of my driveway (2' underwater), so the soil was soft and slippery. I had to hand winch my truck about 40', half of that uphill.

The next morning, my arms were fine, but my leg and butt muscles were quite sore (unaccustomed strain at the positions for crouching and cranking). However, my ME symptoms were greatly reduced. About 24 hrs after starting that exertion, I started feeling much worse. That does match the delay for PEM, but I also ate some potatoes, and I can't tell the difference between PEM and food reactions, so I'm not sure.

The reduction in brainfog and lethargy was certainly nice. I'll have to experiment further with extreme exertion in unaccustomed forms ... without eating problematic foods.