Helping others is a way of life; TRP channels

“Whenever we see something which could be done to bring benefit to others, no matter how small, then we should do it.” — Tai Situ Rinpoche

(SamyeLing.org)

Sometimes getting started is the hardest part.

Notes & links for TRP channel enthusiasts, on chronic pain, gender differences with migraine, IBS/colitis, and the role of magnesium and TRP channels in fetal development:

The condensed version – women are more prone to migraines then men possibly due to a protective effective of testosterone. Estrogen may increase or decrease risk of migraine depending on amounts/balance with progesterone. Either way, magnesium deficiency can increase chronic pain and other TRP channel problems because it is a mineral that helps keep them closed – they are like gates in the cell membrane.

Magnesium deficiency in very early stages of pregnancy or conception can have a negative impact on development of the embryo which can cause problems with physical and/or brain growth which can affect the infant throughout life. Pumpkin seeds has been the short answer I’ve given for years (post) – they are a good source of magnesium and many other nutrients, about one to two ounces, 2-4 tablespoons per day is a healthy serving. Like many things in life too much regularly may not be as healthy. Epsom salt baths are a topical source of magnesium and sulfate which would bypass any problems with digestion making it a good source for people with Irritable Bowel Syndrome or colitis, both of which can be problems linked to overactive TRP channels. (More about magnesium sources.)

Stress can be a cause of overactive TRP channels in addition to the risk of changes occurring during early conception/embryological development.

Other triggers for TRP channels include hot pepper (capsaicin), vitamin D/ and curcumin (a vitamin D analog) a phytonutrient found in turmeric, the yellow spice used in curry powder, ginger, horseradish; volatile chemicals such as formaldehyde, gasoline fumes, cigarette smoke, ammonia; very cold temperatures or very hot temperatures; increased pressure such as might occur during carnival rides or from overeating a large meal or gassy meals with large servings of raw vegetables such as cabbage or broccoli. Cinnamon, mint, vanilla can also activate some types of TRP channels – there is a large variety of TRP channels and they don’t all react to the same triggers and not all types are found in the same organ systems within the body so migraines and bowel troubles may not share the same triggers, but having a place to start can be helpful instead of feeling that everything you eat or do might be a problem.

Interesting hot pepper trivia: “Although both sexes showed sensitivity to capsaicin, males required a four-fold higher dose of capsaicin than females for a similar response (Lu et al., 2009)” (ref 2)

Quotes from an excerpt of ref 1,
(https://www.researchgate.net/figure/Involvement-of-TRP-channels-in-stress-TRPV1-a-member-of-TRP-channel-is-present-in_fig2_234019431) )
Importance of TRP channels in pain:

  • Implications for stress, causal or strong correlation: “altered expression, function and/or regulation of TRPs are key changes which induce patho-physiological conditions like stress, neuropathic pain and cancer.”  
  • “TRPM2 and TRPV4 are involved in oxidative stress- induced cell death of hippocampal neurons (121).” – the hippocampus is an area involved in short term memory and is damaged early in Alzheimer’s disease.
  • “several TRPs can also be activated by estrogen, endrogen, testosterone, cortisol and many other steroids (Table 1)”– so stress could increase TRP channel activity due to inc levels of cortisol. /Speculation: Estrogen mimetics might also be over activating TRP channels./
  • Overactivating TRP channels can also cause IBS symptoms: “over-stimulation of TRPs leads to an influx of excess Ca 2+ which is generally associated with the cell death (126)”
  • “TRPV1 regulates food absorption, emesis, colitis and also regulates the gut – brain axis mainly by responding to endovanilloids and endocannabinoids (132-133).” – colitis is a more severe bowel condition than IBS, has similarities in symptoms though

Re reference 2:
Migraines are 3 times more likely to be a problem for women than men and it may be due to the sex hormone’s ability to activate TRPV1 channels https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102492/ … this info may help with developing more targeted treatments.
“migraineur women exhibited a thicker posterior insula and precuneus cortices compared to male migraineurs & the healthy controls of both sexes (Maleki et al., 2012)”
Testosterone may help protect men from migraines or as severe a migraine if they do have one. It helps modulate activity of TRPM8 channels. Over expression of TRPM8 channels “by a testosterone-mediated mechanism” is seen in prostate cancer.

Re reference 3:
Genetic differences in gene for TRPM8 channels (transient receptor potential melastatin 8) have been identified that are more common in people w migraine sensitivity. They are activated by cold temperatures and/or menthol (mint).

Re reference 4:
TRPM6 & TRPM7 channels and magnesium are known to be critical in embryological development, inc pigmentation/melanin. Mg deficiency during pregnancy can cause significant problems.
TRPM7 & magnesium also critical for dopaminergic cells/Parkinson’s disease. other embryo dev differences w Mg deficiency were seen in the gut & spine (less straight). – a review: TRPM Channels and Magnesium in Early Embryonic Development (4)

TRP channels may become overly active from stress or during fetal development. The symptoms can be difficult to notice a pattern of triggers because the TRP channels have many different ways of being activated. See the G3 excerpt in this document for more details, Child Trauma, Possible Relationship or Chronic Physical Symptoms as an Adult – or for a more condensed version see the graphic below.


“If I had more time, I would have written a shorter letter.” ~ Blaise Pascal

(QuoteInvestigator)
Things that may overstimulate TRP channels.

“Well begun is half done.” – Aristotle

Disclaimer: This information is provided for educational purposes within the guidelines of fair use. It is not intended to provide individual health care guidance. Please seek a health care professional for individualized health care guidance.

References:

  1. Kumar, Ashutosh & Goswami, Luna & Goswami, Chandan. (2013). Importance of TRP channels in pain: Implications for stress. Frontiers in bioscience (Scholar edition). S5. 19-38. https://www.researchgate.net/publication/234019431_Importance_of_TRP_channels_in_pain_Implications_for_stress
  2. Artero-Morales M, González-Rodríguez S, Ferrer-Montiel A. TRP Channels as Potential Targets for Sex-Related Differences in Migraine Pain. Front Mol Biosci. 2018;5:73. Published 2018 Aug 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102492/doi:10.3389/fmolb.2018.00073 Interesting hot pepper trivia: “Although both sexes showed sensitivity to capsaicin, males required a four-fold higher dose of capsaicin than females for a similar response (Lu et al., 2009)
  3. Dussor G, Cao YQ. TRPM8 and Migraine. Headache. 2016;56(9):1406-1417. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335856/
  4. Komiya Y, Runnels LW. TRPM channels and magnesium in early embryonic development. Int J Dev Biol. 2015;59(7-9):281-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685952/

Duty to Warn

Duty to warn is phrase used in medical care regarding an ethical duty to warn patients or research participants or anyone at risk of the potential harm. My own health and my experience helping others has made me appreciate wellness and sharing what has helped or what can be harmful are things I feel ethically it is my duty to warn or inform anyone who might be interested. We are one – your pain is my pain and the Earth needs more health. It is hurting too.

Empathy – feeling emotionally connected can also feel painful, a short article discusses the idea of the pain that may occur with feeling compassion for other’s suffering:

The Agony of Being Connected to Everything in the Universe, (andrewboyd.com)

The words sympathy, empathy and compassion are used somewhat interchangeably however they can refer to slightly different things. In medical settings the care of patients can be affected positively or negatively by how the caregiver provides help. Research with patients receiving cancer treatment found that patients felt that empathy and compassion were beneficial while sympathy was perceived more negatively. Compassion was felt to be most beneficial by the patients. What is the difference? Sympathy seems to be regarded as pity-based remarks or attitude about the chronic illness that was offered without having been asked, with less of a feeling of being understood. Empathy may be closer to feeling emotionally understood and compassion included feelings that the caregiver was acting with love and kindness out of a altruistic – giving mindset. (3) The risks of rudeness in a medical setting and possible value of kindness is discussed in a review of a research study on rudeness in a neonatal clinic setting: A Message to you Rudy, about Rudeness, SGEM#227.

Feeling like there is a physical problem and being told that it must be hypochondria or mental illness is not as helpful as being told that a reason for the symptoms are unknown at this time. Chronic itch, chronic pain and other vague symptoms of inflammation may be labeled as psychosomatic instead of unknown cause. Overactive TRP channels can be involved in chronic itch and chronic pain and the variety of possible substances and other reasons for a flair up in symptoms can make it very difficult to notice the pattern. I would rather be told we don’t know what is causing your symptoms than to be told to see a talk therapist or to be prescribed medications for mental illness that may cause additional symptoms due to side effects. The following chart is something I created after noticing a pattern, a very complex pattern, in my own symptoms and researching what the connection might be —- TRP channels. Not all substances or factors would cause symptoms for all of the conditions or for all people with a certain type of condition, however they may in larger amounts, or they may when the symptomatic condition is in a more severe state of inflammation. In reading about patients with some types of chronic itch symptoms I could feel their itchiness and mental hurt when treated as just difficult patients with anxiety problems – anxiety other extreme itchiness perhaps.

More about chronic itch and inflammatory stress conditions is available within a longer page/chapter I wrote about G3:Relaxation & StressG3.5: Negative stress chemicals may cause symptoms like itching, migraines, pain or IBS. (effectivecare.info) Preeclampsia is a prenatal condition that can become life threatening for the woman and expected infant and it affects a significant percentage of pregnancies – more information about TRP channels and a physical position that might help reduce internal pressure on the channels is available in the section on G5: Preeclampsia & TRP Channels. It is a yoga style position that was recommended to reduce risk of a breech birth during my own pregnancies and I found it relaxing. (effectivecare.info) I feel a duty to warn – a duty to inform other expectant mothers about a simple strategy that might protect their infant from a potentially life-threatening condition.

/Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./

  1. Shah SK, Hull SC, Spinner MA, et al. What Does the Duty to Warn Require? The American journal of bioethics : AJOB. 2013;13(10):62-63. doi:10.1080/15265161.2013.828528. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816221/
  2. Andrew Boyd, The Agony of Being Connected to Everything in the Universe, andrewboyd.com http://andrewboyd.com/the-agony-of-being-connected-to-everything-in-the-universe/
  3. Sinclair S, Beamer K, Hack TF, et al. Sympathy, empathy, and compassion: A grounded theory study of palliative care patients’ understandings, experiences, and preferences. Palliative Medicine. 2017;31(5):437-447. doi:10.1177/0269216316663499.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405806/
  4. Dr. Simon McCormick, SGEM #227: A Message to you Rudy, About Rudeness, Aug. 22, 2018, A Skeptic’s Guide to Emergency Medicine, http://thesgem.com/2018/09/sgem227-a-message-to-you-rudy-about-rudeness/

Why care about health? It’s about statistics.

The rate of cancer incidence has increased greatly in many countries and is expected to continue to increase, particularly in association with the aging of the population. Cancer is more often a diagnosis after age 65.  The rate of thyroid cancer in particular has increased greatly in women. The rate of developing some type of cancer during one’s lifetime is expected to reach 1 in 2 men and 1 in 3 women by the yea 2050, (MedScape) – or a more general 1 in 2 people, (medicalnewstoday) – those are not good odds.

It is common during youth to feel secure about health but our bodies tend to run out of stored nutrients as we age and metabolic pathways that we depend on to rebuild muscle and remove toxins or defective cells can become less effective. A healthy immune system also protects us from our own body’s normal rebuilding/regrowth of new cells. Defective ones are typically removed from growth areas in bone marrow before they enter circulation. Cancer cells are also removed on a regular basis when our immune systems are healthy.

Magnesium deficiency is a topic I keep stressing because the immune cells require magnesium in order to perform the apoptosis, killing, of defective or precancerous cells. The body’s defense systems are well developed but need fuel on a daily basis in order to be able to function as nature designed. While immune cells need magnesium in order to purposefully kill defective cells by apoptosis ( an enzyme is inserted into the cell which causes it to die and then the immune cell engulfs the debris and removes it for detoxification and excretion from the body), a cell that is deficient in magnesium or calcium may also undergo apoptosis due to the deficiency. (magnesium and apoptosis)

Too little Nrf2 may reduce immune system and antioxidant health but too much can be a problem in cancer cells that grow too rapidly. (Nrf2 overproduction and cancer)

Another person writing about the recent research in the area of Nrf2 shares more information about foods that help promote Nrf2 and how nature may have built in a mechanism within some foods that help prevent an over production of the important protein (Nrf2). See: “Activate Nrf2, then optimize: Brussel Sprouts.” – Bill Lagokos (patreon) /Spoiler, if not a fan of Brussel Sprouts the healthy phytonutrient that is discussed is also found in cruciferous vegetables including cabbage, cauliflower, broccoli, kohlrabi, and kale.

I personally am more sensitive to the group, especially if served raw or in larger quantities, but find steamed kale everyday tolerable to my digestive system. The bloating effect may be due to our good guy bacteria enjoying the fiber rich vegetables so much they produce the excess gas – but it can be a sign of healthy bacteria in our digestive tract. Irritable Bowel Syndrome can be affected by any food that causes bloating effects possibly due to TRP channel’s being activated by increased pressure. People with a history of IBS and other chronic pain syndromes may be suffereing from an underlying issue with overactive TRP ion channels. IBS and TRP channels are discussed on this site in a previous post. TRP channels are discussed in more detail with links on another website: Chronic Itch, migraines, IBS and stress; – that is one part frm a longer series: Relaxation and Stress, which is continued in:  Preeclampsia & TRP Channels.

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

And what do osmomechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids have in common?

// 7/1/16 addition: This post is for people suffering from Irritable Bowel Syndrome (IBS) which is not well understood, easy to diagnose or treat, and can be life threatening when more severe symptoms continue long term. The condition can continue for years or be a life long issue that flairs up at times and is less severe at other times.

Dietary tips can be helpful but why some foods seem to trigger symptoms while others don’s has not been well understood either. The common factor underlying why some foods seem to be triggers for many people may be the TRP channels that are found in cells throughout the intestines and actually in most cells of most life forms. //

So what do osmo-mechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids all have in common?

They all may be able to overstimulate Transient Receptor Potential channels (TRP channels) within the gastrointestinal system and cause severe diarrhea in susceptible individuals.

In many cases, the activation mechanism of TRP channels is unclear (Figure 1), but known activators include specific agonists such as mustard oil (TRPA1) and capsaicin (TRPV1), an increase in intracellular Ca2+ (TRPM4, 5), temperature (heat: TRPV1, 2, 3, 4, TRPM4, 5; cold: TRPM8, TRPA1), mechanical or osmotic stress (TRPV4, TRPCs?) and phospholipase C (PLC) activation. TRP channel activity can be further modulated by intracellular phosphatidylinositol phosphates, such as PI(4,5)P2 and membrane potential, but also by inflammatory mediators, cannabinoids and steroids (Nilius, 2007; Rohacs, 2007; Nilius and Voets, 2008).” [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012403/]

The TRP channels are a large group found in many species of life from yeast, to worms, fish and mammels. The agonists/activating chemicals for many of the types of TRP channels have not all been identified as of yet.

One type of TRP channels were formerly called Vanilloid Receptors, and are now called TRPV channels. Vanilloid Receptors were known to be activated by capsaicin found in hot peppers and chili powder. And more recent or less well known research has also found that they can be activated by cannabinoids and steroids, (see the link from the excerpt above), and osmomechanical stress.

Osmo-mechanical stress might be a precursor to edema, excess fluid in the extracellular space; if an organ or cell over fills with fluid it would mechanically be adding physical pressure to the organ or cell — and instead of popping like an overfull water balloon the TRP channels open in response to the physical pressure and let the excess fluid leak out into the extracellular space or into the area surrounding the heart for example. [http://www.ncbi.nlm.nih.gov/books/NBK92821/] Fibrotic heart disease would be adding mechanical stretching stress within the heart. TRP channels are being studied for possible use in preventing fibrotic heart disease. From that research article, we are told that changes in temperature may also activate them:

The activation mechanisms of TRP channel are highly diversified. Some TRP channels appear to be constitutively active, whereas others are activated by Gq-linked receptor activation, oxidative stress, changes of temperature, or an elevation of intracellular Ca2+ [126128]. All the TRP channels appear to be regulated by PIP2 [134137] .” [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874073/]

  • PIP2 = phosphoinositides = phosphatidylinositol phosphates (PIPs) = phosphorylated deriviatives of phosphatidylinositol (PI) [http://www.annualreviews.org/doi/abs/10.1146/annurev.cellbio.21.021704.102317]
  • PIP2 = phosphatidylinositol-4,5-bisphosphate and PI, and phospholipase C (PLC) from the first excerptare involved in cannabinoid metabolism within plasma membranes: [page 9 Kendall et. al., Behavioral Neurobiology of the Endocannabinoid System (Springer, 2009, New York)]

Steroids and hormone D function similarly. And Benicar and curcumin can function similarly to hormone D. And curcumin is a medically active extract from turmeric, a powdered spice that is a main ingredient in curry powder. Turmeric is made from the root of a plant that is biologically very similar to ginger,  which is also a root that is used as a dried spice or  may be used as a chopped vegetable in stir-fry dishes and other foods. Ginger has over 400 active phytochemicals, and one of them might be acting similarly to the curcumin — but that is speculation based on the similarity of symptoms of Irritable Bowel Syndrome that both ginger and curry powder stimulate.

Because — what else do osmomechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids all have in common? — They all may irritate Irritable Bowel Syndrome, (IBS), for some people, along with emotional stress and other things like eating fructose in much quantity (example: from a piece of fruit or fruit juice) or gassy vegetables like cabbage and cruciferous vegetables and beans (gas would be adding mechanical pressure to those TRP channels which might be an over-active culprit in IBS patients).

  • The book, “Tell Me What to Eat If I Have Irritable Bowel Syndrome; Nutrition You Can Live With; Including Dozens of Healthful Mouth-Watering Recipes,” by Elaine Mager, M.P.H., R.D., includes dietary advice and other information about Irritable Bowel Syndrome (IBS). (Warning – most of the recipes contain gluten
  • Re corticosteroids and hormone D:  http://www.oapublishinglondon.com/article/1471

Other diseases that are not well understood but which involve edema and excess fluid entering the area between cells include Chronic Obstructive Pulmonary Disease (COPD) and Congestive Heart Failure (CHF).

So a lack of adequate potassium or magnesium might be involved in allowing too much calcium to enter the interior of cells where it can act as a trigger to increase the flow across the TRP channels even more.

A summary:

/Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./