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Still problem
Cold sensitivity and its etiology--need to solve this urgently
- Thread starter frozenborderline
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Cold sensitivity of TRPA1 is unveiled by the prolyl hydroxylation blockade-induced sensitization to ROS
Mammalian transient receptor potential ankyrin 1 (TRPA1) is a polymodal nociceptor that plays an important role in pain generation, but its role as a cold nociceptor is still controversial. Here, we propose that TRPA1 can sense noxious cold via transduction of reactive oxygen species (ROS) signalling. We show that inhibiting hydroxylation of a proline residue within the N-terminal ankyrin repeat of human TRPA1 by mutation or using a prolyl hydroxylase (PHD) inhibitor potentiates the cold sensitivity of TRPA1 in the presence of hydrogen peroxide. Inhibiting PHD in mice triggers mouse TRPA1 sensitization sufficiently to sense cold-evoked ROS, which causes cold hypersensitivity. Furthermore, this phenomenon underlies the acute cold hypersensitivity induced by the chemotherapeutic agent oxaliplatin or its metabolite oxalate. Thus, our findings provide evidence that blocking prolyl hydroxylation reveals TRPA1 sensitization to ROS, which enables TRPA1 to convert ROS signalling into cold sensitivity.
- Takahito Miyake,
- Saki Nakamura,
- Meng Zhao,
- Kanako So,
- Keisuke Inoue,
- Tomohiro Numata,
- Nobuaki Takahashi,
- Hisashi Shirakawa,
- Yasuo Mori,
- Takayuki Nakagawa &
- Shuji Kaneko
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Mammalian transient receptor potential ankyrin 1 (TRPA1) is a polymodal nociceptor that plays an important role in pain generation, but its role as a cold nociceptor is still controversial. Here, we propose that TRPA1 can sense noxious cold via transduction of reactive oxygen species (ROS) signalling. We show that inhibiting hydroxylation of a proline residue within the N-terminal ankyrin repeat of human TRPA1 by mutation or using a prolyl hydroxylase (PHD) inhibitor potentiates the cold sensitivity of TRPA1 in the presence of hydrogen peroxide. Inhibiting PHD in mice triggers mouse TRPA1 sensitization sufficiently to sense cold-evoked ROS, which causes cold hypersensitivity. Furthermore, this phenomenon underlies the acute cold hypersensitivity induced by the chemotherapeutic agent oxaliplatin or its metabolite oxalate. Thus, our findings provide evidence that blocking prolyl hydroxylation reveals TRPA1 sensitization to ROS, which enables TRPA1 to convert ROS signalling into cold sensitivity.
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Skimming this it seems like cold sensitivity has to do with a type of thermal receptors sensitivity to reactive oxygen species. Since ROS are involved already in ME/CFS , this seems like a possible point of overlap . the paper also mentions we know more about heat sensitivity and signalling of heat than cold ... And that peripheral neuropathy (which I've been diagnosed with) could be involved
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"Some chemotherapeutic agents induce peripheral neuropathy, including cold hypersensitivity, which leads to the discontinuation of the chemotherapy. The platinum-based chemotherapeutic agent oxaliplatin (L-OHP) often causes peculiar acute cold hypersensitivity, unlike other chemotherapeutic agents23."
@frozenborderline you can check Dr Berg video on YouTube "5 reasons for cold intolerance".it was helpful for me.
Usually it means you loose magnesium or iron. So any deficiency that involved in anemia could be a reason - biotin (seems to increase iron half life, once I needed really high dose - 5000 x5 a day to see an effect), other b vitamins, vitamin C. Or,if magnesium on the low side- selenium, iodine and boron really keeps it. (Boron may induce halogen detox, carefully). I say it from my experience. These variants can be true especially if you get colder after taking food, as it was with me when I was deficient in these vitamins/minerals.
(If not ME reasons)
Usually it means you loose magnesium or iron. So any deficiency that involved in anemia could be a reason - biotin (seems to increase iron half life, once I needed really high dose - 5000 x5 a day to see an effect), other b vitamins, vitamin C. Or,if magnesium on the low side- selenium, iodine and boron really keeps it. (Boron may induce halogen detox, carefully). I say it from my experience. These variants can be true especially if you get colder after taking food, as it was with me when I was deficient in these vitamins/minerals.
(If not ME reasons)
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Cold sensitivity may be a symptom of hypothyroidism, anemia, fibromyalgia or vasoconstriction. Anemias, such as, vitamin B12 or iron can cause a constantly feeling cold. There are other conditions that may cause a cold intolerance, including low body weight, high body temperature and low blood pressure.
Differential diagnosis: hypothyroidism, anemia, fibromyalgia or vasoconstriction
Symptoms: weakness, feeling extremely cold, cold hands and feet, shakiness
Differential diagnosis: hypothyroidism, anemia, fibromyalgia or vasoconstriction
Symptoms: weakness, feeling extremely cold, cold hands and feet, shakiness
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Abstract
When exposed to an ambient temperature of 4 degrees C, iron-deficient anemic rats become hypothermic. This lesion is related more to anemia than to tissue iron deficiency, since exchange transfusion to hematocrits over 25 restored normal thermoregulatory performance. Likewise poor cold responses were induced in control rats by transfusion to low hematocrits. Cold sensitivity in all anemic animals was paralleled by poor thyroid responses: there was a significant positive correlation between hematocrit and percent rise in triiodothyronine (r = 0.63) and thyroxine (r = 0.53) during 6 h at 4 degrees C. Basal levels of thyroid-stimulating hormone (TSH) were similar in control and iron-deficient animals: after cold exposure, TSH rose to higher levels in those animals with hematocrits over 25 than in those with lower hematocrits. Diminished O2 delivery to tissues responsible for heat production is probably a major component of the cold sensitivity of anemic rats. The novel finding that thyroid hormone responses are compromised by anemia implies effects on hormonal regulation that may also contribute to this functional lesion.
When exposed to an ambient temperature of 4 degrees C, iron-deficient anemic rats become hypothermic. This lesion is related more to anemia than to tissue iron deficiency, since exchange transfusion to hematocrits over 25 restored normal thermoregulatory performance. Likewise poor cold responses were induced in control rats by transfusion to low hematocrits. Cold sensitivity in all anemic animals was paralleled by poor thyroid responses: there was a significant positive correlation between hematocrit and percent rise in triiodothyronine (r = 0.63) and thyroxine (r = 0.53) during 6 h at 4 degrees C. Basal levels of thyroid-stimulating hormone (TSH) were similar in control and iron-deficient animals: after cold exposure, TSH rose to higher levels in those animals with hematocrits over 25 than in those with lower hematocrits. Diminished O2 delivery to tissues responsible for heat production is probably a major component of the cold sensitivity of anemic rats. The novel finding that thyroid hormone responses are compromised by anemia implies effects on hormonal regulation that may also contribute to this functional lesion.
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My whole body may have *slightly * increased coldsensitivity, maybe bc of anemia or hypomerabolism. But it's more of a neck specific problem. My surgery that initially worked has degenerated a bit and now the neck is really weak and I think the metal hardware is sensitive to the cold and causes spasms and then occipital headache starting in my neck , even when it's not that cold , even when I'm dressed well, etc.
I was better off before surgery , yes I had to wear a neck brace but I not only could be in the cold, I often was better in the cold. I loved snow and cold. Many snowy places have better air. The warmest places in the Us in winter like florida and San diego and all of the southeast, are bad air. The places that are great air are generally all at least a bit freezing in winter. Even death valley and much of the desert of the southwest has night temps that are frosty. But especially places up in the mountains like west Virginia monongahela national forest, or the high altitude pine forests and Mesa's of northern nm, the mountain villages I used to spend time in and jog around in sometimes barefoot even after I got sick and diagnosed with cci, bc that fresh, high altitude cold air was amazing, and snow itself is somehow healing. Now my neck spasms probably bc of the hardware and weakness even when my neck is swaddled with neck warmers and hot water bottles. I'm upset that I'm not getting better, I'm upset I'm getting worse. But I'm also really upset I've had another small thing I used to love, winter, become something I seemingly cant tolerate easily.
I was better off before surgery , yes I had to wear a neck brace but I not only could be in the cold, I often was better in the cold. I loved snow and cold. Many snowy places have better air. The warmest places in the Us in winter like florida and San diego and all of the southeast, are bad air. The places that are great air are generally all at least a bit freezing in winter. Even death valley and much of the desert of the southwest has night temps that are frosty. But especially places up in the mountains like west Virginia monongahela national forest, or the high altitude pine forests and Mesa's of northern nm, the mountain villages I used to spend time in and jog around in sometimes barefoot even after I got sick and diagnosed with cci, bc that fresh, high altitude cold air was amazing, and snow itself is somehow healing. Now my neck spasms probably bc of the hardware and weakness even when my neck is swaddled with neck warmers and hot water bottles. I'm upset that I'm not getting better, I'm upset I'm getting worse. But I'm also really upset I've had another small thing I used to love, winter, become something I seemingly cant tolerate easily.
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I really will be upset and neve forgive anyone if I dont get to have some winter before it's over. Some snow. The top of spruce knob or something like that
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If I missed it bc of combination of lethargy or laziness and my neck spasms that are new fromsurgery, that just seems like unfair torture ,
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Please dont make that happen again
I dont want that reality. I dream of snow
I used to thrive in the cold before they put the alien metal torture implants in me
How could they make something that is good to me bad to me
I dont want that reality. I dream of snow
I used to thrive in the cold before they put the alien metal torture implants in me
How could they make something that is good to me bad to me
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I'm also having back tightness symptom of retethering, and along with the increased cold sensitivity came extreme fatigue and lethargy and a reversal of my initial gains from surgery
I would say Shanti1 has hit the nail on the head with A compromised paraventricular nucleus within a dysfunctional hypothalamus: A novel neuroinflammatory paradigm for ME/CFS.
I would also suggest that microglial dysfunction leading to a cytokine storm, leading to neuroinflammation is driving the dysfunction in the paraventricular nucleus. The chaos (from immune microglial dysfunction) is causing regulatory dysfunction of the brain region.
This part of the brain is essentially the control center for all the sensory stress input from the outside world, whatever form that may be.
Stress will cause you to get worse, stress comes in many forms not just psychological but physical also from any sensory input you have as a human being. This area of the brain feeds the HPA axis (flight or fight).
I hope this is not too technical, was neccessary to explain what I believe to you. Hope it can help. Any questions? waiting to respond.
Hope you are better by now
I would also suggest that microglial dysfunction leading to a cytokine storm, leading to neuroinflammation is driving the dysfunction in the paraventricular nucleus. The chaos (from immune microglial dysfunction) is causing regulatory dysfunction of the brain region.
This part of the brain is essentially the control center for all the sensory stress input from the outside world, whatever form that may be.
Stress will cause you to get worse, stress comes in many forms not just psychological but physical also from any sensory input you have as a human being. This area of the brain feeds the HPA axis (flight or fight).
I hope this is not too technical, was neccessary to explain what I believe to you. Hope it can help. Any questions? waiting to respond.
Hope you are better by now
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I would wonder why I dont feel that much colder throughout my whole body but I do in my neck where there is hardware
And also why I didnt have cold sensitivity that extremely before I had surgery that put hardware in my neck. I had bodily stress and severe illness before that. If what you are describing is the theory, why wasnt it causing extreme cold sensitivity beforehand... I was sick before I I just didnt have much cold sensitivity
And also why I didnt have cold sensitivity that extremely before I had surgery that put hardware in my neck. I had bodily stress and severe illness before that. If what you are describing is the theory, why wasnt it causing extreme cold sensitivity beforehand... I was sick before I I just didnt have much cold sensitivity
Hi frozenborderline,
so you know we all have me/cfs here. But we are all different, severity, symptoms.
The condition is caused by the immune system being dysfunctional.
When you are active and move around or suffer stress, your bodies dysfunctional immune system goes overdrive and causes a cytokine storm.
When you get an injury like a cut, your body sends immune cells to that specific area.
Your surgery was stressful and you are dealing with a stressful situation and on top of that you may have caught a virus that can also trigger a post viral condition like ME/CFS called Long Covid.
I myself have suffered from cold sesitivity so bad I could not step outside in late autumn/winter/early spring as body would recoil in intense nerve pain with electrical pulses and severe muscle cramps that were extremely hard to deal with.
I could tell the weather from inside my home I was so sensitive.
Dysfunctional immune system affects regions of the brain by affecting Microglial cells (part of brain immune system amoung other things) causing wide spread dysfunction in areas that regulate body temp for example and your sense of the outside world via your nervous system.
Hope this helps explain.
so you know we all have me/cfs here. But we are all different, severity, symptoms.
The condition is caused by the immune system being dysfunctional.
When you are active and move around or suffer stress, your bodies dysfunctional immune system goes overdrive and causes a cytokine storm.
When you get an injury like a cut, your body sends immune cells to that specific area.
Your surgery was stressful and you are dealing with a stressful situation and on top of that you may have caught a virus that can also trigger a post viral condition like ME/CFS called Long Covid.
I myself have suffered from cold sesitivity so bad I could not step outside in late autumn/winter/early spring as body would recoil in intense nerve pain with electrical pulses and severe muscle cramps that were extremely hard to deal with.
I could tell the weather from inside my home I was so sensitive.
Dysfunctional immune system affects regions of the brain by affecting Microglial cells (part of brain immune system amoung other things) causing wide spread dysfunction in areas that regulate body temp for example and your sense of the outside world via your nervous system.
Hope this helps explain.
If you've had surgery, then an anaesthetic could have written off your B12, causing you to become deficient if you weren't beforehand. I think this may be at least one of the keys to why you feel as you do right now.
The other thing is thyroid problems. I have hypothyroidism, the first symptoms I had included feeling very cold in my extremities and also incredibly tired. You might want to check out your levels.
The other thing is thyroid problems. I have hypothyroidism, the first symptoms I had included feeling very cold in my extremities and also incredibly tired. You might want to check out your levels.
This is good info. If you had Nitrous oxide while in surgery it could have oxidised the B12 making it unable to take part in biological processes. You will even come back as not defcient from a test and all of the B12 will be unable to be utilised by the body.
So deficient but lab tests that say otherwise.
Before I discovered I was deficient in B12 many years ago, I was crazy bad with ME/CFS. Cold sensitivity was at its max. But after correcting and many years on I still had the cold sensitivity but no way as severe.
B12 deficiency happens because of the disruption to the normal functioning of the whole body by immune system, which then affects enterohepatic (bowel/liver) recycling of vitamin B12.
I hope to explain what I believe over time or as others make mention of relevant subjects.
Thyroid patients tend to suffer B12 issues because it also is involved in immune system and metabolism. In fact many conditions with an immune type connection have B12 issue in them from what I see as I consumed the internet over the years.
If you take B12 which I suggest is a good idea, it would be better to consume Hydroxo or Methyl not Cyano, due to better utilisation. All standard B12 in USA is cyano but you do have the ability to buy intramuscular B12 unlike me now.
Sorry for the long post
So deficient but lab tests that say otherwise.
Before I discovered I was deficient in B12 many years ago, I was crazy bad with ME/CFS. Cold sensitivity was at its max. But after correcting and many years on I still had the cold sensitivity but no way as severe.
B12 deficiency happens because of the disruption to the normal functioning of the whole body by immune system, which then affects enterohepatic (bowel/liver) recycling of vitamin B12.
I hope to explain what I believe over time or as others make mention of relevant subjects.
Thyroid patients tend to suffer B12 issues because it also is involved in immune system and metabolism. In fact many conditions with an immune type connection have B12 issue in them from what I see as I consumed the internet over the years.
If you take B12 which I suggest is a good idea, it would be better to consume Hydroxo or Methyl not Cyano, due to better utilisation. All standard B12 in USA is cyano but you do have the ability to buy intramuscular B12 unlike me now.
Sorry for the long post