Pain, Pain Medications, Addiction, and Chronic TRPV1 and TRPA1 Activation: How They Connect

Tranquility Foods
Apr 29
3 min read

Updated: May 27

Chronic pain affects millions, and understanding its root at a molecular level can help guide safer treatments. Two receptors, TRPV1 and TRPA1, play a large role in pain signaling. Here’s how their activity leads to serious pain—and why drugs like oxycodone are both helpful and risky.

At the core of this issue are two important molecules: TRPV1 (Transient Receptor Potential Vanilloid 1) and TRPA1 (Transient Receptor Potential Ankyrin 1). These receptors are found on nerve endings that detect and signal pain. TRPV1 is activated by heat, acidity, and capsaicin—the chemical in chili peppers that makes them burn. TRPA1, meanwhile, responds to irritants, cold, and inflammation.

Our research has revealed that many foods commonly regarded as healthy, specifically synthetic forms of vitamin A, can activate the TRPV1 and TRPA1 receptors. When these receptors are repeatedly activated due to our dietary choices, ongoing inflammation, or injury, the nerves become hypersensitive. This phenomenon, known as sensitization, means that even mild triggers can lead to intense pain, a condition referred to as hyperalgesia.

Chronic Pain, Oxycodone, and Mu Opioid Receptors

Pain resulting from chronic TRPV1 or TRPA1 activation is often stubborn and hard to manage with common over-the-counter treatments like acetaminophen or ibuprofen. As a result, patients and doctors may turn to stronger medications, such as opioids. Oxycodone is one of the most commonly prescribed opioids for severe or persistent pain because of its powerful effects.

Oxycodone works mainly by activating mu opioid receptors (MOR) in the nervous system. These receptors are responsible for blocking pain signals, particularly those amplified through TRPV1 and TRPA1. By activating mu receptors, oxycodone effectively turns down the signal generated by overactive pain receptors, providing much-needed relief for those suffering from chronic pain.

How Do These Receptors Interact?

The interplay between TRPV1/TRPA1 and mu opioid receptors is important to understand. Research has shown that these receptors are often present on the same nerve cells. When oxycodone activates the mu receptor, it reduces the excitability caused by TRPV1 and TRPA1, blunting the pain response.

However, chronic use of opioids like oxycodone can also upregulate, or increase the activity of, TRPV1, which in turn can accelerate the development of tolerance. This means patients need higher doses of the drug to achieve the same level of pain relief. A useful analogy is building tolerance to spicy food: the more you consume and the hotter the peppers, the less sensitive you become to the heat. However, the craving for the dopamine release and the euphoric feeling that comes from activating the receptors leads you to crave spicier peppers more frequently in order to regain that pleasurable sensation.

The Downside: From Pain Relief to Addiction

Unfortunately, this relationship also helps explain the risks of dependence and addiction with opioids. As patients develop tolerance, they tend to require progressively higher doses—not only to achieve pain relief, but also to experience the feelings of pleasure or euphoria that opioids can produce. This cycle can lead to physical dependence, and when the drug is stopped suddenly, both pain and withdrawal symptoms can feel intolerable. Chronic TRPV1 activation also makes mu opioid receptors less responsive, which increases the risk for rapid tolerance and difficult-to-control pain. Research suggests that addressing TRPV1 signaling may help limit opioid side effects and reduce the risk of addiction.

In summary, chronic activation of TRPV1 and TRPA1 can drive intense pain that many common treatments cannot control. Opioids like oxycodone provide relief by blocking pain signals at the level of the mu opioid receptor, but the interplay between these pathways encourages tolerance and addiction. New developments in pain management research focus on targeting TRPV1 or TRPA1 directly—with the hope that such strategies will help patients achieve lasting relief without the risks of escalating opioid use.

At Tranquility Foods, we are dedicated to raising awareness about the seemingly harmless chemicals in our food that can continuously activate the TRPV1 and TRPA1 receptors. Join us to learn more about how to combat unnecessary stress, inflammation, and pain, and to discover what true tranquility means for you and your loved ones.

Key Takeaways

• Chronic TRPV1/TRPA1 activation triggers stubborn pain that’s hard to treat.

• Oxycodone and other opioids relieve this by silencing pain signals through mu opioid receptors.

• Over time, the interplay between these systems builds tolerance and risk for addiction.

• Mitigating chronic TRPV1/TRPA1 activation with informed nutritional choices, may help treat pain better without as many opioid side effects.

Research Links