What do Mint, Chili, Marijuana & Cinnamon have in Common?
Plants and mammals play a chemical dance that allows us to interact with knowledge and expectancy. From the food perspective we use different plants or plant extracts to obtain certain, predictable sensations or tastes. We seek them and use them with deliberation. But how are these sensations registered? What are the health implications and is there an underlying system?
There is an underlying system, the equivalent of a chemical radar system that allows us to navigate the world, warning us of problems & invaders, as well as reminding us of friends and the familiar. This is achieved through the same super family of receptors called TRPs. Pronounced TRiPs they are a class of receptors that you may have never heard of, but use every day of your life. Science has slowly been peeling back the veil and now we know a lot more about TRPs and their potential impact on our health and wellbeing. TRPs stands for “transient receptor potential” and activating these receptors change the permeability of cations, like sodium or calcium, and in so doing affects the electrical nature of the special nerves that detect them and then inform the brain of their presence. TRPs are your chemical radar system used to detect friends and foes.
The sensations under their control are important to daily function. They dictate quality of life and allow us to navigate through our environment. Sensations include: pain, heat, coolness, taste, nausea, cough and pheromones. They also mediate local responses like blood flow, cough, histamine & hormone release.
So the list of plant chemicals that work via TRPs is actually quite extensive. However, before we reveal how and why they work let me outline some fundamentals so we can better navigate this new terrain.
Concept #1: Rapid Feedback
Firstly the feedback needs to be rapid. Biologically, that means it’s neural. Secreting chemicals into the blood to act on the brain or elsewhere may happen but that would be slow. Imagine a chef tasting the food, if it took 30 minutes to get the feedback then he may have added way tragically too much of an ingredient in the meantime. So the feedback is rapid, and therefore neural, in order to influence behavior.
Concept #2: Sensory Nerves
Having established that the responses to plant chemicals are mediated by nerves, we need to ask which nerves are involved? They are called sensory afferents, which just means they transfer sensations to the brain. Sensory afferents have their own collage of neurotransmitters, which are often peptides. They also have a peculiar twist in that while they are sending the information to the brain via the spine, they have local curly loops that mediate local reactions.
So when you react to something on your skin your brain is told that it itches, so you scratch it to remove the offense, and the local response may be redness, swelling & histamine release. So local and brain events are co-ordinated by these sensory afferent nerves.
Concept #3: Origin affects the Sensation
Best example of this is itch & nausea. The same type of nerves are involved in both itch and nausea, the sensations are very different because the brain processes them according to the origin. So itch relates to skin nerves, and nausea is felt when stomach or gut nerves are activated. This differentiation helps to direct the reactions like itch or vomiting. Sometimes there are interactions that allow both pathways to get to the brain at once. The best example are opioid narcotics, they remove a neural barrier in the spine that dictates traffic flow for these sensations. As a consequence one of the major side-effects of opioids are nausea and itch, events that are readily apparent after surgery.
Sensations: Role of TRPs
So TRPs are a family of receptors on these sensory nerves that react to these phytochemicals (plant derived) and some internal chemicals, and elicit the response. There are at least 6 major families and within those families lots of subsets that are defined by individual specific agonists or chemicals that activate the receptors. An excellent, detailed review was published by Premkumar (ACS Chem Neurosci. 2014 Nov 19; 5(11): 1117–1130) and here are some examples
Heat & Pain vs. Cooling & Analgesia
Let’s take the TRPV receptor as it is well characterized. The most well known receptor is the chili pepper or capsaicin receptor. TRPV1 mediates the sensations of heat and pain. Everyone is familiar with the sensations associated with ingestion of chili peppers that are excessively hot (for your setting).
Activation of TRPV1 also establishes a heightened reactivity to other stimuli. For example, if you are sunburnt and take a hot shower you may feel pain. What was once pleasurable is now painful (called thermal hyperalgesia). Note that heat and acid from tissue injury also activates TRPV as well as the list of phytochemicals.
One way to counteract the pain associated with TRPV activated by heat or capsaicin is to use TRPM with menthol, which is the active principle in mint or peppermint. TRPM activation is associated with a cooling sensation, which is familiar to everyone after menthol or peppermint. So the strategy to opposes heat & pain induced by capsaicin is to use menthol. Both actions are mediated by TRPs, albeit different ones and via different subset of nerves. For this reason menthol is used as an analgesic widely used in OTC sports creams.
There are lots of dynamics at play. Sticking with the chili pepper receptor (TRPV1) if that is stimulated for a long time it becomes desensitized. We all know people that eat chili hot food without issues, and that is because they have desensitized their TRPV1 receptors. In essence they become unresponsive and less effective.
There are also chemicals that activate the receptors but mildly. The pharmacological concepts related to this include low potency and partial agonist. Sometimes they can prevent the actions of a more potent stimulant by occupying the receptors preventing access.
The family of receptors called TRPs drive sensations that allow us to navigate the world, especially our interactions with plants that we encounter or eat. They are responsible for diverse responses like coolness, heat, pain, taste, itch, nausea and drive local protective responses in our barriers like skin, gut and lungs. They are portals that allow us to make choices that are desirable and warn us of danger. They provide flavor to food and form a chemical radar for our wellbeing.
Science is busy unraveling their mysteries for improved therapies. For many of us they are familiar. They represent our spices, our food additives, our traditional medicines and treatments. Out this old knowledge new opportunities are becoming apparent.