Opioids are powerful painkillers, or analgesics, that millions of people use to manage their pain. But, how do opioids work to induce their analgesic effects and reduce pain?
First, what are opioids?
Opioids are a class of drugs that is naturally found in the opium poppy plant. Some opioids are used to treat pain, while others are illegal drugs that some abuse to get high, such as heroin. Some opioids are made entirely in the lab, including fentanyl. Others are natural opioids such as morphine, which are made from substances taken from the poppy plant. These natural opioids are used to make semi-synthetic opioids such as heroin, oxycodone, and hydrocodone. The body also makes its own endogenous opioids to relieve pain, such as endorphins.
Photo of the opium poppy plant
Humans have been using opium for centuries to treat pain. Thomas Sydenham, a 17th-century English physician once said, “Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium.”
Even though we have more options to treat pain today than we did 400 years ago, opioids are still an important and effective tool for doctors to manage their patient’s pain.
Opioids are effective painkillers, but they can also have a lot of side effects. These side effects include dizziness, nausea, and addiction. Opioid overdose can also cause respiratory depression and potentially lead to death.
How do Opioids Work?
Opioids induce their effects by binding to receptors on neurons in the periphery, such as nerves in the arms or legs, or to neurons in the spinal cord or brain. There are three types of opioid receptors: mu (μ), kappa (κ), and delta (δ) opioid receptors. Each of these receptors serves a different function.
- There are three types of mu opioid receptors (MOR):
Mu-1 receptors are located outside the spinal cord in the brain and on neurons in the periphery. They play an important role in opioid-induced pain relief and dependence.
Mu-2 receptors are located both in the brain and spinal cord. They are responsible for the euphoria and physical dependence associated with opioids. Binding of opioids to Mu-2 receptors in the brainstem can also lead to respiratory depression, which is slow and ineffective breathing. If left untreated, respiratory depression can lead to death.
Mu-3 receptors cause vasodilation, which is when your blood vessels widen, lowering the blood pressure. This can deprive organs, especially the brain, of the oxygen they need to function.
Together, mu opioid receptors are responsible for opioid analgesia (pain relief) and many of the pleasurable feelings associated with opioid use.
- Kappa opioid receptors (KOR), on the other hand, are responsible for the dysphoric effects of opioids, such as depression and anxiety. They can also produce modest pain relief.
- Finally, delta opioid receptors (DOR) are located in the spinal cord where they produce analgesia. But, DORs are also located in the limbic system, which controls emotions and some types of memory. Binding of opioids to DORs in the limbic system leads to dependence and reinforcing behaviors associated with opioids.
By activating these receptors, opioids can change the activity of neurons throughout the nervous system.
Naloxone:
When someone is experiencing an overdose, they are treated with an antidote called naloxone. Naloxone binds to all these opioid receptors more tightly than any other opioid. Thus, if someone is experiencing an overdose, naloxone knocks the opioid out of its receptor and blocks other opioids from binding to it and stopping the effects of opioids. Naloxone is regarded as a “miracle drug” by many, as it has saved the lives of thousands of people. As I mentioned earlier, one of the biggest reasons people die from opioid overdose is that they stop breathing due to respiratory depression. This is due to binding of opioids to Mu-2 receptors in the brainstem. Naloxone prevents that binding, and thus restores breathing of an individual who has overdosed.
This photo depicts some of the regions in the central nervous system where opioids exert their effects. Opioids can influence breathing through their actions on the brainstem, and they can influence emotion and memory through their actions on the limbic system.
The Placebo Effect:
Interestingly, placebos use similar mechanisms to opioids to induce their effects.
The placebo effect is the idea that “your brain can convince your body a fake treatment is the real thing.”(2) Let’s assume you are given a placebo, that can be a vitamin or a sugar pill for example, you are then told that this treatment is very effective at treating pain. This changes your expectation of that treatment, and in doing so the placebo activates the reward pathway in your brain. This then leads to the release of endorphins and dopamine. Endorphins are then able to bind opioid receptors and lead to pain relief.
Endorphins are natural opioids that are released by the body when it’s stressed. They are responsible for what is called the “runner’s high,” which is a feeling of euphoria and pain relief that allows runners to complete grueling marathons.
Some people believe that placebos are a hoax, that they don’t actually have any effect. But, the placebo effect is powerful. Moreover, it is important to have positive expectations about your treatment, as expectations can have significant effects on outcomes.
Citations:
Dhaliwal, A. (2020, August 29). Physiology, Opioid Receptor. Retrieved December 14, 2020, from https://www.ncbi.nlm.nih.gov/books/NBK546642/
Publishing, H. (n.d.). The power of the placebo effect. Retrieved December 14, 2020, from https://www.health.harvard.edu/mental-health/the-power-of-the-placebo-effect
Pinch, B. (2016, September 14). More Than Just a Sugar Pill: Why the placebo effect is real. Retrieved December 14, 2020, from http://sitn.hms.harvard.edu/flash/2016/just-sugar-pill-placebo-effect-real/
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