Pain Sensitivity...

Fight…. or flight!. I know what my Pain Sensitivity is over the last eight years.

It was first tried to be controlled by Tramadol. A medicine I found to be allergic to the first week. Then came

Indomethacin.

One that burned holes in my stomach, so prilosac, for the stomach, the It was opioids, and morphine. Enough that the pharmacists thought I was giving it to someone on their death bed.

I was able to get off all these, except prilosac when a proper diagnosis came. Two meds work to block Pain in Multiple Sclerosis. Are Lyrica and Cymbalta combination. They need to start with name brands, as generics don't work. Gabbapentin is another good one. I am on over twenty five medicines, to control Pain and my multiple Sclerosis.

A interesting report of DNA was done by Sanogenetics.com. It shows some DNA they know is related to Pain. Enclosed is their report, I find interesting. Everyone has different Pain thresholds. I am sure DNA will shed light on many others.

https://palousemindfulness.com/MBSR/week0.html

Thanks for reading, and leave me a comment!

Joe

Pain Sensitivity

How does genetics influence the way we experience pain?

Pain Sensitivity

Complexity Level:Complex

Heritability- low -10%

Genetic variation in these sites has been associated with different levels of susceptibility to & risk of chronic pain.

rs4680

- This means that you are likely to have an intermediate pain threshold.

rs1042713

- This means you have a normal risk of experiencing chronic pain

Thermal pain

rs25531

- This means that you are likely to have a higher threshold for acute thermal pain.

A pulled muscle in the back or leg can send some of us to the couch for days whereas others seem to more easily recover. How can we explain differences in pain sensitivity and recovery? Could the answer be in our genes? Scientists have been studying the question for a long time and the answer is: “it’s complicated”. Susceptibility to pain appears to be dictated by interactions between your environment and your genetics.

Fight…. or flight!

Many of the genes found to be associated with pain sensitivity contribute to the production of adrenaline and serotonin .

Both adrenaline and serotonin are 'neurotransmitters', which act as messengers in the brain to carry information. Adrenaline is often known as one of the “stress hormones” and is responsible for the famous “fight or flight response”. Increased levels of adrenaline raise the heart rate, elevate blood pressure and boost energy supplies. In other words, adrenaline prepares the brain to react to immediate danger. In patients with chronic pain, some genetic variants have been found on a gene called COMT, which is known to be involved in the regulation of adrenaline. Genetic variation in the site called rs4680 has been associated with different levels of susceptibility to chronic pain. People with two G's in this position are much more tolerant to chronic pain!

Genetic variation in another gene called ADRB2 also influences adrenaline levels and has also been suggested to play a role in pain sensation. One genetic variant near ADRB2 has been associated with chronic pain: rs1042713. Curiously, the adrenaline related genes mentioned in this article may also be associated with sleep dysfunction and anxiety.

Pleasure or pain?

The second neurotransmitter system that seems affected in patients with chronic pain is the serotonin pathway. Serotonin is often prescribed as an anti-depressant and is popularly thought to contribute to feelings of well-being and happiness. This description does not do serotonin justice, as it does far more in our body than regulate emotions and works in complex and intricate ways. In the context of pain for example, serotonin can act as an analgesic (painkiller) or as hyperalgesic (pain enhancer), depending on where it acts in the body. Several genes controlling serotonin production are involved in susceptibility to pain. The HTR2A gene codes for a protein that acts as a 'landing pad' or receptor for serotonin. The serotonin transporter gene SLC6A4 is also involved in pain perception. If you have two C's at rs25531, you are more likely, on average, to be more sensitive to thermal pain (such burns or frost bites).

What does this tell us?

This is only a snapshot of the many genes that are involved in pain sensitivity. It is important not to forget that the perception of pain can also be influenced by psychological factors. A recent study suggested that swearing out loud while immersing your hand in cold water can help relieving the pain . Overall, more research is needed to truly understand the biological nature of pain. As our understanding improves, there may be opportunities to develop more personalised treatments to acute and chronic pain.

Image credit: - Unsplash

References

[1]The phenotypic and genetic signatures of common musculoskeletal pain conditions.

[2]The science of why swearing reduces pain.

Glossary

[SNP]

SNP stands for 'single nucleotide polymorphism' and refers to regions of DNA that vary between individuals.

Multiple Sclerosis

Complexity Level:Complex

Heritability- medium -48% - 64%

Multiple Sclerosis (MS) is a rare autoimmune condition, caused by a body’s own immune system attacking its central nervous system.

A quick note: this article is not intended as diagnosis or treatment advice.

As well as the genes covered here, around 200 more have also been found to contribute to MS, along with environmental factors, so this is very far from being a full picture of your risk level.

Different variations in some of the HLA* family of genes and certain T-cell related genes have been found to relate to different levels of risk.

rs3135388

effect:3Higher risk

rs4959039

effect:1.4Higher risk

rs6897932

effect:1.08Higher risk

rs2104286

effect:1.4Higher risk

*Read on for more detail on exactly how these genes and environmental factors like vitamin D deficiency affect MS risk.

This is my Data from SanoGenetics.com. Quite a interesting read. They picked up my Data from 23andme.com, so not a complete set of DNA used. I have asked their permission to use this page in my blog, as this information may help scientist and researchers. Tellmegen.com has a complete set of my DNA, along with Allofus.org

Vitamin D may also play a role in MS. A detailed report is available by emailing me, as I will retest to see if some items Tellmegen.com has shown interferes or not with vitamin D.

JoeY
A song that I thought would fit this DNA from yester year

Time in a bottle plus the classic Sound of silence

TURKMENISTAN - WHY ARE THE STREETS SO EMPTY?

This report covers several of the genes known to play a role in Multiple Sclerosis (MS). This article is not intended as a diagnosis or to provide treatment advice, but as an educational and informational tool that is personalised to your genetic data. Beyond the genes covered here, there are around 200 genes which have been identified that also contribute to MS. Non-genetic factors such as Vitamin D also play a role in MS, and are explored in this report .

What is Multiple Sclerosis?

Multiple Sclerosis (MS) is a rare autoimmune condition which is caused by the body’s own immune system attacking its central nervous system .

It is characterized by a wide variety of symptoms including problems with vision, movement and speech .

The risk of developing MS is influenced by many factors including genetics. Several genes have been identified in influencing the development of MS, many of which regulate the immune system.

Which genes influence a person's possible development of Multiple Sclerosis?

The Human Leukocyte Antigen (HLA) is a family of MS related genes that make a group of proteins called the HLA complex which plays a role in helping immune cells communicate with each other. The HLA complex helps the immune system to differentiate between foreign attackers (e.g. bacteria or viruses) and the body's own tissues. In MS, the immune system is unable to distinguish between the body's own tissues and a foreign attacker due to a miscommunication between immune cells.

Different variations of HLA genes have been found to relate to the risk of developing MS. Two of those variations are HLA-DRB1 (rs3135388) and HLA-G (rs4959039). Allele rs3135388(T) in HLA-DRB1 has been associated with a 3 to 6-fold higher risk of developing MS.

Allele rs4959039(G) in HLA-G has shown to be associated with around a 2-fold higher risk for developing MS.

What environmental factors influence a person's chances of developing Multiple Sclerosis?

One of the environmental factors which has been linked to the development of MS is vitamin D deficiency. People with MS have lower levels of 25-hydroxyvitamin D3 (25-OHD3) in their bodies. Research suggests that increasing Vitamin D levels in people with a predisposition to developing MS may reduce risk of developing the condition.

In the kidney, skin and immune cells, 25-OHD3 is processed and activated by a gene called CYP27B1. This means that the final level of active vitamin D3 is dependent not just on Vitamin D levels, which is influenced by factors such as sun exposure and diet, but also genetic factors in the CYP27B1 gene.

Low levels of CYP27B1 will likely influence the available amount of active vitamin D3 present in the body. As a result, studies have shown that Individuals with allele rs703842 (T), which is correlated with lower levels of CYP27B1, are on average more likely to be affected by MS.

What are T cells and what role do they play in developing Multiple Sclerosis?

The IL7RA gene produces a protein that participates in immune system response and in T cell (a type of immune cell) development. Some genetic variants in IL7RA result in decreased protein levels. It has been shown that carriers of the allele rs6897932 (C) produce less IL7RA, and people with allele rs6897932 (C;C) have about 2 fold higher risk for MS development. On the other hand, the (C;T) and (T;T) variants are associated with protection against MS.

T Cells, mentioned previously, are an important part of our body's immune system and are involved in ‘adaptive immunity’, which includes a system for remembering past threats and responding to those threats when they occur again. MS, like many autoimmune diseases, is in part the result of T Cells not functioning correctly, and attacking the bodies own cells.

IL2RA produces a protein that is involved in T-Cell growth, and genetic variants in IL2RA are associated with MS risk. The rs2104286 (A) allele is associated with a higher risk of MS, while the rs2104286 (G;G) allele is associated with lower MS risk. One of the FDA-approved treatments for MS, daclizumab, works by blocking IL2RA.

In conclusion

There are around 200 genes which could influence a person’s development of Multiple Sclerosis, many of which regulate the immune system. Some genes may increase or decrease the risk of developing MS directly, whereas others may increase or decrease the risk of associated conditions such as vitamin D deficiency that can influence a person's likelihood of developing MS. However, genetics is just a small factor among many other factors (including environmental, immunologic and infectious factors) which influence a persons likelihood of developing MS.

Research into immunology, epidemiology, genetics and infectious agents is essential to increase our understanding of the causes of MS as well as helping to discover more effective treatments.

References

[1]National MS Society: What Causes MS?

[2]Mayo Clinic: Multiple Sclerosis

[3]Sano Genetics: Multiple Sclerosis

Glossary

[Environmental Factors]

Environmental factors are external influences that can affect an individual's health and wellbeing.

[Immune System]

The organs and processes of the body that provide resistance to infection and toxins.

[Immunological]

Relating to the structure and function of the immune system

[Infectious Agents]

Is generally used to describe and encompass any material that can cause an infection that can lead to a disease. There are four main classes of infectious agents: bacteria, viruses, fungi, and parasites.

[Protein]

Proteins are large, complex molecules that play many critical roles in the body.

[SNP]

SNP stands for 'single nucleotide polymorphism' and refers to regions of DNA that vary

But even more DNA using DNA from tellmegen.com

rs10492972 AG (or TC if reading the complementary DNA strand)) G (or C) is the risk allele

KIF1B gene conflicting reports; possible slight increased risk for multiple sclerosis

rs12722489 IL2RA gene AG a slight increase in risk of developing multiple sclerosis G is the risk allele

rs6498169 AG KIAA0350 gene 1.14x risk of multiple sclerosis A is the risk allele

rs10984447 AG DBC1 gene 1.17x increased risk for multiple sclerosis A is the risk allele

rs12044852 AC CD58 1.24X risk C is the risk allele

rs12708716 AA CLEC16A 1.6x risk of type-1 diabetes and other autoimmune diseases (such as MS) A is the risk allele

rs4149584 GG TNFRSF1A normal risk A is the risk allele

rs3135388 AG (or TC) HLA-DRA 3x higher risk of multiple sclerosis A (or T) is the risk allele

Ever Changing MS

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