Category: oxidative stress

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G3.6.1.7: TRPV channels – the comfort of vanilla, the heat of capsaicin.

Before leaving the topic of “getting to know your TRP channels,” I’d like to introduce the vanilloid family. They were among the first TRP channels to be identified with lab techniques. This is all very tiny stuff, difficult to work with compared to a craft or construction project in the full size world we can see without a microscope. It is easy, however, to see when someone is scratching or wincing from pain, so the lab technicians and research scientists are to be commended for their fine eye for microscopic detail.

Vanillin or vanilloid receptors can have a calming effect on the body – baked goods with vanilla have a little extra besides love soothing the body. However some types of TRVP channels can also be stimulated by hot pepper due to its capsaicin content. (G3.99) Capsaicin is the active phytochemical that causes a feeling of “hot” when hot peppers are eaten – because it activated a TRPV channel which activates a nerve to send a signal to the brain that is most likely to be interpreted as “hot” although some people learn to enjoy the feeling, or may be genetically different and experiencing slightly differently than other people who couldn’t imagine eating very hot, hot peppers (G3.100)

The aroma of vanilla can lead to an emotional feeling of comfort even without eating a food containing the phytochemical that can activate the TRPV channels. “Aroma” does involve nerves being activated in response to a chemical in the air that enters the nostrils. Tiny amounts of “vanilla” aroma are entering the nose and physically activating TRPV channels which physically activate nerve signals that tell the brain “something” happened. This time it wouldn’t be as obviously “hot” as the capsaicin though, the vanilla is activating a different TRP channel which would activate a different nerve. If hot peppers had been experienced before the memory of them would be strong enough to remember not to eat them or touch them again. Making “noxious” chemicals, irritants or toxins, is a plant defense mechanism to encourage animals to not eat the plant unless it is ready for the seeds to be spread. A delicious fruit smells delicious when it is ripe and the seeds are ready to be “planted” somewhere other than right where the plant is growing. Some plants make seed pods that catch the wind or have burrs and attach to animal fur as animals walk by, and other plants make delicious fruit or other nutritious seeds to encourage animals to eat them, and carry the seeds elsewhere to be “planted” later (whenever the animal defecates). Nature is amazing.

Vanilla is a delicious smelling seed pod so the plant must want its seeds to be eaten. For delicious history and recipe information see Primer: Vanilla Part One and Two, by Jasmine, a culinary blogger.  (G3.102, G3.103)

We learn from previous experiences when to avoid something and when to reach for a second helping. If the brain had experienced home baked cookies in the past, then the scent of them baking any time in the future might set off an expectation of delicious food and activate saliva glands in addition to causing a calm or pleasant emotional response to the aroma of vanilla or a comforting memory from childhood. Aromas can also be tied to emotional responses that were learned in childhood or at any time in a trauma situation. Positive memories associated with an aroma may be triggered by re-experiencing the favorite fragrance or negative memories might also be triggered by a reminder of something associated with the trauma.

Cancer treatments can be so nauseating that patients are counseled to avoid favorite foods during the first few days after the treatment in order to prevent negative associations of nausea being linked to their favorite food.  When feeling “under the weather” there is a natural instinct to want to tempt the appetite with a comfort food – but if it is most likely going to be thrown up and the hope is that a few nutrients get absorbed before that happens then a bowl of oatmeal or a entree from an expensive restaurant would be equally unappealing on the way back up and the unusual meal might be more likely to cause memories of the experience. So – the common sense recommendation from dietetics eat the oatmeal while feeling sick or something neutral and save the favorites for later.

TRP channels – what were they again?

Physiology and Pharmacology of the Vanilloid Receptor, (G3.98) Excerpt: “In addition to the contribution of the vanilloid receptor as a target of the neurogenic inflammation underlying different diseases, TRPV1 is gaining interest for the treatment of neuropathic, postoperative and chronic pain and, recently, for the therapy of epithelial disorders [epithelial = skin or membrane]. Thus, for instance, topical capsaicin or resiniferotoxin have been used in postherpetic neuralgia, diabetic neuropathy, postmastectomy pain and arthritis [64,103]. Recently, TRPV1 has been clearly validated as a key target for management of chronic pain in bone cancer [42]. As a result, the development of specific TRPV1 antagonists is a central focus of current drug discovery.” (G3.98)

To review: magnesium is the ion that is needed inside of the cell to power the TRP or ion channel’s ability to stop some chemicals from entering the cell’s interior while allowing other chemicals to enter. Magnesium is the soldier at the gate with the energy to stand sentry all day and night – if present. If there is magnesium deficiency, the sentry with energy to keep the gate shut is gone and any chemical floating around in the fluid outside of the cell that is small enough to fit through the open ion channel is able to  flow through the unguarded gates. The capsaicin that can treat pain when used topically is over stimulating the receptors to the point where they are no longer sending any pain signals. When there is a magnesium deficiency then calcium itself can be a cause of pain.

Inside the interior of the cell calcium can activate the cell function and cause it to overwork to the point of cell death similarly to the “excitotoxins” such as glutamate or aspartic acid, both used in the food supply as flavorings – they also excite the tongue’s taste buds. MSG, aspartame and Neotame were included in the list of chemicals that might activate TRPA1 receptors which are associated with several chronic pain and chronic itch conditions.

 Calcium signals the cell to overwork, which leads to inflammation and signals of pain. Nerve signals are activated by inflammatory chemicals which are also “pain” signals as perceived by the brain – inflammation hurts because it is activating “pain” nerves. “Inflammation,” “oxidative stress,” and “pain” are all experienced as the same thing to the brain. So if someone at work is annoying you and you just can’t stop thinking about it – you might be physically hurting yourself, consider taking a walk in nature or buying a fern instead. Smelling vanilla scented essential oil products may also provide some comfort.

  • The research team suspect that “calcitonin gene related peptide (CGRP)” is involved in producing changes underlying the condition of “pain” and “inflammation” for the condition of arthritis at least. Inflammatory chemicals produced in one area of the body could travel and send nerve signals that led to inflammatory pain symptoms being felt in other areas of the body – so over-thinking can hurt? Read more: New Study Proves that Pain is Not a Symptom of Arthritis, Pain Causes Arthritis. Newsroom, University of Rochester Medical Center, urmc.rochester.edu, Sept. 29, 2008, (G3.109)

However CGRP has also been found to be involved in helping to suppress severity of symptoms in autoimmune diabetes. Providing CGRP therapy in an animal based research study helped reduce oxidative stress chemicals and the damage they can cause to pancreas cells that can eventually lead to developing autoimmune diabetes. (G3.114) Researchers working with human patients who have diabetes theorize that those people with a reduced response to stress are the people who seem to progress to diabetes most quickly. (page 19, G3.115) Chemicals similar to CGRP have also been tested therapeutically for heart disease patients and has been found to have some benefits for reducing hypertension, cardiac hypertrophy, and heart failure. (G3.116)

As a dietitian the question I next ask when I learn about a chemical in the body that seems to promote health is how do we make it for ourselves? How can we better assist patients to make it for themselves rather than being dependent on a daily medication? What does a person need to make CGRP ?

Drumroll – an answer does already exist in medical research – magnesium. Providing magnesium directly to an area of bone with a fracture in need of healing, was found to effectively promote increased bone healing – possibly due to a measured increase in levels of CGRP.  (G3.117, G3.118)

So would you rather have a medical professional provide you a daily medication at a profit to the medical system – or be informed of ways to change your diet and lifestyle so that you could make the life saving chemical naturally the way healthy people do, everyday?

Like most things in life – too much CGRP isn’t good either. Genetic differences may be involved in risk for migraine as elevated levels of CGRP have been found in patients with migraines. Attempts to block the chemical Substance P were found to be ineffective but use of CGRP agonists/blockers were found to help patients with migraine. (G3.119)

And sugar is something that is a negative when eaten in excess. Too much sugar in the diet typically also means fewer nutrients are being consumed as refined sugar has no additional B vitamins or magnesium, while a piece of bread or fruit would provide some nutrients in addition to the naturally found sugars. Excess sugar in the bloodstream leads to an increased loss of magnesium by the kidneys because the mineral is necessary in order to remove the excess sugar from the blood and add it to the urinary waste stream. (G3.120) B vitamins are needed in order for the body to be able to break down the molecules of sugar so the stored energy is released. Smaller waste chemicals are produced from the larger sugar molecule that will also need to be excreted by the body as a normal part of metabolism (metabolism is roughly equal to all of the body’s many chemical, energy and digestive cycles). A diet with excess refined sugar has also been associated with heart disease risk. (G3.121)

See a healthcare provider for medical advice, diagnosis or treatment.

  • 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.
  • The Academy of Nutrition and Dietetics has a service for locating a nutrition counselor near you at the website eatright.org: (eatright.org/find-an-expert)

References: 

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G3.6.1: “Calcium sparklets” and Oxidative Stress

G3.6.1.1: “Calcium sparklet” – a burst of energy from a TRP channel; can be measured but not seen.

Calcium and magnesium are both electrically active ions – ions are atoms of an individual element rather than being a more complex molecule that is made of a combination of several different elements. Water is made of one atom of oxygen and two atoms of hydrogen for example. Calcium and magnesium are both individual elements rather than being molecules. They are both considered to be essential trace minerals that we need in our diet on a regular basis or we would get sick and eventually die without enough of either one. They each have an ionic charge of +2 and can exchange one or two electrons.

Ions can typically donate or receive electricity by sharing or receiving one or two electrons. Sodium and potassium are essential trace minerals with a charge of +1, they can exchange one electron. the energy is in the form of electromagnetic radiation, which is also what make “light., (G3.105), so while our human eyes may be too big to detect the “light” of a microscopic burst of energy from the flow of calcium across a TRP channel – maybe a tiny spark might be visible to that microscopic world.

Magnesium sparklers – a spark of life.

Many people may be more familiar with holiday “magnesium sparklers” than with “calcium sparklets” as the mineral magnesium is flammable and can be used to make Fourth of July sparklers, which are a festive sight during celebrations of the U.S. Independence Day.

 

G3.6.1.2: Calcium sparklets can be caused by high blood sugar – hyperglycemia. (G3.108)

  • Calcium and diabetic vascular dysfunction, Focus on “Elevated Ca2+sparklet activity during acute hyperglycemia and diabetes in cerebral arterial smooth muscle cells: “This report is also the first to describe a molecular mechanism by which hyperglycemia produces increased [Ca2+]i in VSM and suggests that this mechanism of Ca2+ sparklet activation may be uniquely initiated by hyperglycemia.” (G3.108)

Calcium sparklets are not a good thing, not in excess at least, they represent an open gate into the interior of the cell, allowing a crowd to enter instead of invited guests only. (G3.106, G3.107, G3.108) Too much energy or other types of chemicals suddenly being available on the interior of a cell can over activate it and even lead to the death of the cell.

“Excitotoxins” refers to chemicals that can cause a cell to become overactive if the chemical is allowed to enter the interior of the cell. TRP channels are the gateway that selectively lets in some things and keeps out everything else. If TRP channels aren’t able to do their job properly, then too much of “everything else” is able to rush into the cell and that may be what happens for some people more than others. If the everything else includes MSG from a recent meal or the alternative sweetener aspartame then overactivity of the cell may result.

Calcium itself acts as a messenger chemical that can trigger action when it is on the interior of the cell and can act as an “excitotoxin” and lead to the death of cells. During normal health magnesium is in greater abundance inside of the cell and calcium is found in larger amounts than magnesium in the fluid surrounding the cells and within blood plasma.

The alternative sweetener aspartame, brand name Nutrasweet, or the more concentrated version Neotame may both act as excitotoxins. The food flavoring ingredient monosodium glutamate also may over excite cells. What they have in common is a free amino acid that can act as a signal to the brain cell to tell it to get busy doing whatever it usually does, “just get busy, go, keep going, there’s no “off” here, move it . . .” an excitotoxin is the worse drill sergeant ever, and eventually the cell runs out of nutrients and/or builds up waste products of metabolism, and may even die. That’s a dramatization, but roughly that is the story – “oxidative stress” equals “waste products of metabolism.”

G3.6.1.3: Oxidative Stress > metabolic waste products > “TRPA1 sparklets.”

To return to the excerpt and list from the previous section, the first list of chemicals known to activate TRPA1 channels included waste products of metabolism. Metabolism is the chemical deconstruction of a larger molecule into smaller parts. Enzymes are necessary that are specific to the exact type of chemical transformation. Toxins can collect without enough of the right type of enzyme to metabolize them into smaller chemicals that are safe or can be excreted more easily by the kidneys.

  • The summary and excerpt: The TRPA1 receptor is directly activated by calcium levels inside of the cell, and a variety of toxins or “noxious” (irritating) substances that are produced as a normal part of “oxidative stress” otherwise known as “inflammation” including, “4-hydroxy-2-nonenal, hydrogen peroxide, hypochloride, hydrogen sulphide, 15-delta prostaglandin J2 [25–28].” and irritants from the environment or diet can also activate the TRPA1 receptor, *1.“mustard oil (allyl isothiocyanate: AITC) [29], *2. cinnamaldehyde [30, 31], *3. allicin [32, 33] and *4. formalin [34]…”. (G3.25) Serotonin and other “Inflammatory mediators, such as bradykinin…[19, 35]” (G3.25) can make the receptors more sensitive which can lead to increased responsiveness of nerve endings – more pain (G3.25) or itch. (G3.24)
  • And a new excerpt about oxidative stress and metabolites that are produced within the body, some would activate TRPA1 channels: “Reactive oxygen species (ROS)”(G3.93) formed from oxidative stress were found to activate the TRPA1 channels in the cerebral arteries but not in other areas of the vascular system, “NOX-induced activation of TRPA1 sparklets and vasodilation required generation of hydrogen peroxide and lipid-peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated cerebral arteries.” (G3.93).

“Increased TRPA1 sparklet frequency” (G3.93) can be caused by chemicals that are produced during oxidative stress – which can be caused by emotional or physical reasons. The significance is that it means more calcium or other chemicals could be rushing through the open channel in the membrane wall. Calcium can also be an activating substance as was mentioned in the first summary and excerpt. This is complex chemistry and is just meant to be an introduction to the topic of oxidative stress in relation to conditions of chronic pain and itch. That second excerpt is from an additional list and is about chronic migraine – who are the people who might be more likely to have overactive TRPA1 channels? – quite a few besides those with sensitive skin or pain problems. A more complete list is in the next section but it is likely an incomplete list.

G3.6.1.4: “People with overactive TRPA1 channels” may include people with symptoms of:

  • “chronic itch” (G3.24);
  • “chronic arthritis” (G3.25);
  • “inflammatory bowel diseases (IBD: ulcerative colitis, Crohn’s disease)” (G3.76);
  • people with an Irritable Bowel Syndrome (IBS) may also have had a history of child trauma, domestic violence or sexual abuse:  “As Leserman and Drossman (2007) note, patients with a history of physical or sexual abuse in childhood, or intimate partner violence, have 1.5 to 2 times the risk of reporting gastrointestinal symptoms or having a functional gastrointestinal disorder.,” (G3.94); and trauma survivors may also have comorbid chronic pain conditions such as fibromyalgia: “Van Houdenhove et al. (in press) found that 64% of patients in a group for FMS or Chronic Fatigue Syndrome had at least one type of either child or adult trauma. More concerning was that 39% of the group reported abuse during childhood and as adults, indicating a lifelong pattern of abuse. Although these findings are somewhat mixed,” (G3.94);
  • a medical hypothesis suggests TRPA1 channels may be involved in many chronic pain and airway conditions and also diabetes: “Furthermore, TRPA1 is also involved in persistent to chronic painful states such as inflammation, neuropathic pain, diabetes, fibromyalgia, bronchitis and emphysema.,” (G3.95);
  • symptoms of “diabetic hypersensitivity” (G3.96)  might feel or sound like: “Don’t touch me it hurts.” Symptoms of mechanical hypersensitivity may feel like being physically over sensitive to any sensation. Any touch may be experienced as “pain” or “itch” instead of being pleasant. Symptoms of hypersensitivity associated with diabetes have been found to respond to TRPA1 channel antagonists – chemical inhibitors – a medicine in other words. (G3.96) Reducing the over activity of the TRPA1 channels would help resolve the underlying problem but overmedicating would be a risk. Too much inhibition, too much of the medication could be dangerous to long-term health as the TRPA1 channels play important functions throughout the body.;
  • “chronic migraine,” “cluster headache,” (G3.77); “Reactive oxygen species (ROS)”(G3.93) formed from oxidative stress were found to activate the TRPA1 channels in the cerebral arteries but not in other areas of the vascular system, “NOX-induced activation of TRPA1 sparklets and vasodilation required generation of hydrogen peroxide and lipid-peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated cerebral arteries.” (G3.93);
  • preeclampsia may involve overactivity of the TRPA1 channel, it also has mechanico-sensitive properties or other TRP channels  – more research is needed: (G3.78, G3.79, G3.80, G3.81, G3.82, G3.83);
  • chronic respiratory conditions involving “airway inflammation” such as “asthma” or “COPD,” overly dry airways may be a problem causing difficulty with completely emptying the lungs (G3.84);
  • cardiac issues such as Congestive Heart Failure may involve TRPC channels, (G3.85), which are not activated by the food type items on the list below but which are likely to be activated by cannabinoids which are #8 on the list below, (G3.89, G3.90);
  • male infertility due to motility issues in the sperm, (G3.87, G3.88). TRPC channels (G3.89) can be activated by Phospholipase C (G3.90) which suggests they can be activated by other phospholipids as well. So a deficiency or gene difference affecting their production endogenously may be involved in male infertility involving motility. More research is needed. In the meantime formaldehyde is definitely not beneficial for fertility in women or men. There is more research available regarding exposure risks for female reproductive health (G3.91) than for males.(G3.92)

G3.6.1.5: People with overactive TRPA1 channels may be sensitive to:

And now we return to the list from the section on the last page. It is greatly expanded now with more food items and other possible substances that can activate TRPA1 channels and TRPC channels, gathered from the research about the list of conditions that might be at increased risk for overactive TRP channels. The TRP channels are all membrane channels but there are many individual types and several categories. The basic form and function is similar however and is described and illustrated in an article about the TRPC channel and cardiohypertrophy associated with Congestive Heart Failure, which was included in the previous list.  (G3.85)

  1. Mustard:  “mustard oil”, (G3.25); “Isothiocyante derivatives constitute the main pungent ingredients in wasabi (allyl isothiocyanate), yellow mustard (benzyl isothiocyanate), Brussels sprouts (phenylethyl isothiocyanate), nasturtium seeds (isopropyl isothiocyanate) and capers (methyl isothiocyanate). Allyl isothiocyanate is the major active ingredient in mustard oil.” (G3.67); Yellow mustard is the condiment used in many ways in cooking. It is a spice made from a small seed that is dried and powdered. It has medicinal value for a variety of conditions. Mustard oil applied topically as a massage oil is reported to provide relief for pain due to arthritis. (G3.68) Wasabi is a type of horseradish like seasoning used in Japanese cooking.It is a root vegetable that also has many medicinal benefits. (G3.72) Brussel sprouts are a vegetable that look like tiny cabbages and are botanically related to cabbage. They are very healthy in many ways and might be worth trying in smaller quantities, steamed more thoroughly rather than raw or lightly steamed or sauteed.(G3.71) Nasturtium seeds can be pickled and used in cooking similarly to capers. (G3.69) Capers are a pickled product with a peppery taste which resemble peppercorns, however they are made of the springtime buds of the caper plant which are picked when they are the size of peppercorns, and are preserved in a pickling brine. Capers are used in salads or savory dishes. (G3.70)
  2. Cinnamon:  “cinnamaldehyde”, (G3.25); Cinnamon is a spice used in cooking which is made from the inner layer of bark from a plant. It is dried and powdered and used in baking or savory dishes. Medicinally a ½ teaspoon of cinnamon per day has been found helpful for improving blood sugar control. A half teaspoon is a large amount for a single serving but some people enjoy it at breakfast stirred into a bowl of hot cereal. (G3.43, G3.67))
  3. Onion or Garlic: “allicin”, (G3.25); (G3.41) To be more precise – the raw garlic contains allicin; baked or roasted garlic would be less likely to still have allicin present. It would likely be similar for onion, raw or lightly sauteed might be a problem while caramelized, baked, or roasted might be tolerable. (G3.67)
  4. Formaldehyde: “formalin“, (G3.25); chemically the two are very similar: (G3.42); and formaldehyde is found in the environment and as a metabolite of some alternative sweeteners and other dietary sources. (G3.56) See the next section (which was posted first on this site) for more information on sources and ways to avoid Formaldehyde.
  5. “(Winter-green),” (G3.67); Wintergreen is a natural flavoring herb in the mint family. It is typically used as an essential oil as a flavoring in many foods and other types of products. It has medicinal benefits related to it containing the chemical that acts as the pain killing ingredient of aspirin.(G3.73)
  6. “eugenol (Cloves)” (G3.67); Cloves are used in a traditional holiday decoration to make an aromatic dried ornament from an orange. The tack like cloves are poked into the rind of a fresh orange and then the fruit is allowed to dry and it shrinks and smells good for a long time without spoiling if it was allowed to dry thoroughly. Cloves for use in cooking or baking are ground into a powder and used in baking and also in savory dishes and chutneys. The spice and essential oil also have medicinal benefits. The essential oil has numbing properties and in traditional medicine is applied topically to the gums for relieving the pain of a toothache.(G3.74)
  7. “and gingerol (Ginger).” (G3.67); – a root with medicinal properties and commonly used in cooking as a minced or chopped vegetable and is used in dried and powdered form as a spice in savory and baked dishes and may be served dried and candied and used as a candy or chopped and used in baked goods or chutneys.Ginger has many medicinal benefits and has been found helpful for the relief of arthritis pain when used in a quantity that would be equal to about a half teaspoon of the dried powder. Pregnant women should avoid large quantities of the herb or vegetable or candy as miscarriage may be a risk. (G3.75)
  8. “Δ9-tetrahydro-cannabinol (THC) and cannabinol (an oxidation product of THC).” (G3.67); The herb cannabis also known as marijuana has many medicinal benefits and  is the most significant source of THC but some foods also have some cannabinoid content. The topic of food sources of cannabinoids and risks and safe use warnings are discussed in the section I. Addiction or Starvation?. Medicinal benefits are discussed in detail in the textbook Endocannabinoids: The Brain and Body’s Marijuana and Beyond, editor and Chapter Three by Emmanuel S. Onaivi, et al., (CRC Press, 2006, Boca Raton, FL), which is available online as a pdf:  (I.Endocannabinoids: Full Text pdf)

See a healthcare provider for medical advice, diagnosis or treatment.

  • 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.
  • The Academy of Nutrition and Dietetics has a service for locating a nutrition counselor near you at the website eatright.org: (eatright.org/find-an-expert)

References: 

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G3.6: Antihistamines may help if there is a genetic tendency to overproduce histamine.

Genetic differences in more than 70 genes have been associated with increased itchiness, see summary at the end of this section. (G3.24) Calcium and serotonin levels may be involved in increased itch or arthritis pain signals being sent or perceived. (G3.25) Scratching an itch is considered rude and a chronic itch is often considered funny however it isn’t fun.

Some background information:

Too much or too little calcium and magnesium can affect pain, itching, and mood. The minerals are both electrically active, and provide energy for ion channels which control the transport of messenger chemicals like serotonin across cell membranes – such as nerve cell membranes which might feel like a sensation of itchiness or pain.     

Excess serotonin may be involved, (G3.26, G3.27), and scratching an itch can make the urge to scratch more intense, even worse afterwards, even though there may be a temporary feeling of relief while scratching. (G3.28) Adequate magnesium is essential for reducing pain in arthritis or at least may help reduce pain levels. (G3.27) An antihistamine may help for some types of itching related to genetic conditions. (G3.29)

Excess dopamine levels can also be a cause of an overwhelming urge to scratch – see “grooming behavior” in section 7. When to Report?. The solution there is to figure out why dopamine levels are that elevated. Elevated dopamine can be a symptom of hyperthyroidism but it can also be associated with other conditions.

  • An Itch You Just Can’t Scratch; NIH-funded study identifies proteins that may cause chronic itch. Summary points: The HTR7 gene was found most closely associated with chronic itch in an animal based study, however over 70 genes were found to be more expressed, more active in lab animals with chronic itch. The gene expression of the HTR7 gene was most active in the mice with the worst symptoms of scratching compared to the mice with the least sensitivity. The activity of the TRP1 receptor was also increased in animals with more symptoms. (G.24)
  • Transient receptor potential ankyrin 1 (TRPA1) receptor is involved in chronic arthritis: in vivo study using TRPA1-deficient mice. Summary points: The TRPA1 receptor is directly activated by calcium levels inside of the cell, and a variety of toxins or “noxious” (irritating) substances that are produced as a normal part of “oxidative stress” otherwise known as “inflammation” including, “4-hydroxy-2-nonenal, hydrogen peroxide, hypochloride, hydrogen sulphide, 15-delta prostaglandin J2 [25–28].” and irritants from the environment or diet can also activate the TRPA1 receptor, *1.“mustard oil (allyl isothiocyanate: AITC) [29], *2. cinnamaldehyde [30, 31], *3. allicin [32, 33] and *4. formalin [34]…”. (G3.25) Serotonin and other “Inflammatory mediators, such as bradykinin…[19, 35]” (G3.25) can make the receptors more sensitive which can lead to increased responsiveness of nerve endings – more pain (G3.25) or itch. (G3.24) *See the next section for more information about the chemicals in bold font and where they may be found in the diet or environment.

*People with overactive TRPA1 channels may be sensitive to:

  1. Mustard:  “mustard oil”
  2. Cinnamon:  “cinnamaldehyde'” (G3.43) );
  3. Onion or Garlic: “allicin,” (G3.41)
  4. Formaldehyde: “formalin,” chemically the two are very similar: (G3.42) and formaldehyde is found in the environmental and as a metabolite of some alternative sweeteners and other dietary sources. (G3.56) Environmental sources include which would include first and second hand smoke, poorly ventilated air or smog, especially when there is brand new flooring or other new plastic or vinyl  material in the living area, it  can release volatile chemicals including formaldehyde at levels that can make a sensitive person feel ill. Metabolites of the breakdown of the alternative sweetener aspartame and Neotame include menthol and formaldehyde. (G3.44) Older packages of fruit juice also may contain increasing amounts of formaldehyde as the product ages, more of the chemical is produced from other chemicals.

Magnesium, Opioids, and Neuropathic Pain.

This list and this section got much longer actually, and eventually led me back to a topic I’ve written about in 2011, and which is one of the underlying causes of overactive TRP channels. Fortunately it also has a simple solution, (G3.101), but – unfortunately – it is so simple a solution that it isn’t profitable – unfortunately for individual patient’s health and quality of life and unfortunately for the economic health of individuals and nations and businesses who are being overcharged by the medical industry for healthcare that isn’t always effective and sometimes causes harm.

It is so effective a solution for improving mood and pain and muscle cramp type symptoms that I’ve been sharing the information online since at least 2011 and the article I shared was research from 2009, (G3.101), – so the clock is ticking on how soon the evidence based medical research will reach the individual patient who is in pain. The racers at the starting line are the physicians and nurse practitioners and other health professionals who make recommendations for opioid medications in an attempt to block pain instead of trying to find and resolve the cause of the pain.

What is a nerve signal? “Pain” or “no pain”? or “on” and “off”?
Pain, however, should not just be blocked without trying to understand the cause. It is a message from the body desperately asking for help but it is not always a clear message. Pain in one area of the body may have to do with an issue in another area of the body. Instead of blocking the pain signals we need to listen to them more carefully and try to figure out what the pain signals mean and how to resolve the underlying cause of the pain. Something might be missing and need to be added back into the diet or something might be happening in excess either in the diet or lifestyle habits and need to be stopped or moderated.

Nerve signals are not specific to send the brain a message of “pain” that exclusively means “pain;” a nerve signal is more of an “on” or “off” and might indicate a variety of extremes: too hot or too cold, or too rough or too light (ticklish), or too hot peppery, (capsaicin, (G3.100), more on that later), or too mustard oily. The nerve signal is simply telling the brain that “something” happened – figure it out captain of the ship – and fix it – such as remembering to wear gardening gloves before handling wild mustard weeds, especially if you have diabetic hypersensitivity.

The TRP channels are the bridge between the world and the nerve signal. There are many types and they can respond to specific temperatures, so some might activate when it is very cold and some might activate when it is very hot. Some might react to the hot pepper and some might react to the mustard oil. They would all tell the same nerve – “something” extreme happened.

Mustard oil can cause an extremely itchy reaction. It is used to induce “hypersensitivity” in lab animals to study the condition in relation to diabetic hypersensitivity. This will be discussed in the next section in more detail. (G3.96) Wearing gloves may be advisable when pulling a patch of wild mustard if you tend to have sensitive skin or allergic reactions.  (p124, G3.97)

Antihistamines taken daily can be helpful if excess histidine is a problem.

Antihistamines taken as a daily precaution may be helpful for people with overly sensitive skin if the sensitivity is related to a tendency to overproduce histidine. (G3.29) If that is an issue, then taking an antihistamine medication daily may also help for some types of chronic pain as well, more will be included in the next section. Acupuncture is a traditional therapy that may help reduce the overactivity of TRPV channels and reduce the production of the inflammatory peptide Substance P and other cytokines. Acupuncture can affect both the opioid and the cannabinoid receptors – but without needing the prescription or having to experience the side effects! (G3.104)

See a healthcare provider for medical advice, diagnosis or treatment.

  • 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.

The Academy of Nutrition and Dietetics has a service for locating a nutrition counselor near you at the website eatright.org: (eatright.org/find-an-expert)

References:

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G3.5: Negative stress chemicals may cause symptoms like itching, migraines, pain or IBS.

Our bodies don’t have specific receptors just for sensing “pain.” Pain is a sign that something is wrong in the body and is sensed in a variety of ways. In medical terminology there are two main types of “pain.”

  • Nociceptive pain is associated with physical damage to the body or by sensations of pressure or heat or extreme cold. It might be due to pressure from a cancer tumor. Nociceptive pain might be described as “sharp, aching or throbbing.”
  • Neuropathic pain is caused by physical damage or pressure on nerves. It might also be due to a cancer tumor but one that is pressing on a nerve. Nerve damage can also be due to some nutrient deficiencies such as vitamin B12,  (G3.13), or other “Nutritional imbalance, alcoholism, toxins, infections or auto-immunity.” Neuropathic pain often is described as “a burning or heavy sensation, or numbness along the path of the affected nerve.” (G3.14)

Some types of pain such as migraine headaches may involve both nociceptive pain due to the pressure of inflammation or dilation of blood vessels an neuropathic pain from pressure on nerves by dilated or inflamed blood vessels.

    The next part gets complicated, some background information:

  • Calcitonin is a hormone released by the thyroid that promotes lower blood calcium levels by reducing bone resorption, (G3.15) (Bone resorption: breakdown of the bone and release of minerals, (G3.16)).
  • Calcitonin Gene-Related Peptide 1 and 2 (CGRP 1: (G3.17) and CGRP 2: (G3.18)) cause dilation of blood vessels in the heart and brain and throughout the body. Its prevalence in the Central Nervous System (CNS) also suggests that it may also have a neurotransmitter or neuromodulator role.

CGRP is produced by nerve cells in the brain and throughout the body. The protein has a role in sensations of pain. It is a member of the calcitonin family of proteins and exerts its effects at receptors that are formed from two other types of receptors.

The CGRP protein has two commonly found forms, one helps reduce pain and one helps increase it – luck of the draw. The alpha form of the protein may help reduce pain while the beta form is associated with migraine, temporomandibular joint (TMJ) pain, psoriasis and irritable bowel syndrome (IBS). The beta form is largely produced in keratinocytes found in the epidermis layer of skin. The alpha form is the type produced more within sensory nerves. (G3.19) (Psoriasis is an eczema-like condition believed to be autoimmune in nature.)

After a physical injury like a bump on the shin, inflammation causes an increased output of the Calcitonin Gene-Related Peptide (CGRP) and an inflammatory protein that is called Substance P, possibly for peptide, which is another word for protein. The release of the peptides follows shortly after an inflammatory event and shortly the chemicals are released there is  edema and plasma leakage in the surrounding area. (G3.20) The inflammatory peptides are also released in increased amounts during migraine headaches. (G3.21) The peptides increase the dilation of blood vessels and cause increased leakage from blood vessels (edema) and “degranulation of mast cells.” (G3.19) (G3.21)

Levels of CGRP increase in people who suffer from migraines and a type of prescription medication, called sumatriptan, which has been found helpful to stop migraine pain, has also been found to inhibit the release of CGRP in migraine patients. The medication may be inhibiting the release of CGRP by increasing intracellular levels of calcium. The “cytokine TNF-α” may be involved in migraine pain. (G3.21)

That was the background – the bottom line – magnesium deficiency can make the body more susceptible to the negative effects of CGRP, Substance P and chronic stress. And a chronic stress situation combined with chronic magnesium deficiency may lead to the development of inflammatory conditions like migraines, fibromyalgia, PTSD, or Irritable Bowel Syndrome. The magnesium deficiency associated with the inflammatory peptides CRGP and Substance P may be causing an increase in the level of the cytokine TNF as early as two days after a deficient diet was begun in a research study with lab animals. (G3.22)

So an Epsom salt bath or foot soak may relieve itch by providing the body with a form of magnesium that can be absorbed through the skin bypassing any GI problems that might underlie a chronic magnesium deficiency. It isn’t uncommon to have a diet low in magnesium but it is also not uncommon in the food supply. Problems with poor absorption or increased kidney or bowel loss are common causes of chronic magnesium deficiency.

A variety of tips for reducing Substance P levels are included in the article Trichodynia, Pain, and Substance P. Exercise, hobbies that use repetitive motions of the hands such as knitting, and stretching exercises may help reduce excess levels of the inflammatory chemical according to the article on the website drwardbond.com, see the article for more details: (G3.23)

See a healthcare provider for medical advice, diagnosis or treatment.

  • 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.

The Academy of Nutrition and Dietetics has a service for locating a nutrition counselor near you at the website eatright.org: (eatright.org/find-an-expert)

References: