From Ibuprofen to Acetaminophen: How Do Pain Relievers Work?

Analgesics, also known as painkillers or pain relievers, are medications that most people have used at some time or another for a variety of pain. It might be a bad headache, a pulled muscle, or back pain. In fact, analgesics are the most commonly purchased over-the-counter drugs in the US.

Pain and Inflammation

Pain is an incredibly complex physiological response that acts as a warning signal to the body, letting it know when to slow down. Pain is sensed by what are known as nociceptors, which are free nerve endings designed to detect harmful stimuli, such as injury or inflammation. When these nociceptors sense that something has been damaged, they send electrical signals through the peripheral nerves to the spinal cord and brain. 

Inflammation, a common cause of pain, occurs when the body's immune system responds to injury or infection, releasing chemicals like prostaglandins to begin healing. The brain processes these signals, interprets them as pain, and immediately tells the body to protect itself as a response. This intricate signaling pathway ensures that the body takes action to prevent further harm and start the healing process.

Pain Relievers 

Pain relievers work in a few different ways with the same goal—to prevent the brain from perceiving sensory input from nociceptors as pain in the way it would normally. Non-steroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, block enzymes that produce chemicals causing inflammation and pain. Acetaminophen works mainly in the brain to reduce pain signals and lower fever. Both types help manage and ease pain by targeting these pathways, allowing relief from discomfort.

Knowing what types of pain relievers work and when to use them is a valuable skill. That's why more and more courses, from a first aid level all the way up to online FNP programs, are teaching their students about what pain relief to use and when. 

Non-Steroidal Anti-Inflammatory Drugs

When it comes to the most common over-the-counter pain relievers, there are a few main types. As we mentioned before, non-steroidal anti-inflammatory drugs (NSAIDs) include Ibuprofen (Advil), aspirin, naproxen, diclofenac (Voltaren), and a few others. 

NSAIDs are a class of medications that reduce the big three: pain, fever, and inflammation. They work by inhibiting the activity of cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. These enzymes are crucial in the production of prostaglandins, which, as we have already touched on, are chemicals that promote inflammation, pain, and fever as part of the body's natural healing process. By blocking COX enzymes, NSAIDs reduce the synthesis of prostaglandins, leading to decreased inflammation and, therefore, pain.

These drugs are incredibly common and have been widely used to treat conditions such as headaches, muscle aches, arthritis, and menstrual cramps. While effective, NSAIDs can have side effects, particularly with long-term use, including gastrointestinal issues like stomach ulcers and bleeding, as well as an increased risk of cardiovascular events. Therefore, it is important to use NSAIDs as directed and consult a healthcare provider for prolonged use.

Paracetamol 

As you may have noticed, paracetamol, also known as Acetaminophen, has yet to be mentioned. That's because it isn't an NSAID yet precisely because of the potential side effects for many NSAIDs; paracetamol has become increasingly popular. The funny thing is we don't know exactly how it works. Research is ongoing to pinpoint its exact mechanism of action. 

However, paracetamol is believed to work primarily in the central nervous system. Much like NSAIDs, paracetamol inhibits the production of prostaglandins in the brain by blocking the enzyme cyclooxygenase. However, the particular COX paracetamol block is COX-3, which still reduces prostaglandin levels. However, unlike NSAIDs, paracetamol has minimal anti-inflammatory effects and does not significantly affect COX enzymes outside the brain. This makes it less effective for treating inflammation. 

It is generally considered safer for long-term use compared to NSAIDs, as it has a lower risk of gastrointestinal issues. However, excessive use or overdose can lead to severe liver damage, so it's important to stick to recommended dosages and consult a healthcare provider if you need advice.

Opioids

Much has been written about the American opioid crisis, and while they pose very real dangers when abused, opioids are an entire class of drugs that have been used as pain relievers for over 8000 years. 

Opioids work by binding to their very own receptors in the brain. When someone consumes opioids, they bind to one of the brain's opioid receptors and inhibit the release of neurotransmitters that would otherwise send signals to the body, letting it know that something is wrong. 

The reason opioids get abused lies in what is known as the 'pleasure circuit.' When opioids bind to opioid receptors, they block pain signals and prompt the release of dopamine, a neurotransmitter linked to feelings of pleasure and euphoria. By enhancing dopamine release, opioids create intense feelings of euphoria and relaxation. While this can provide significant pain relief, it also leads to a heightened risk of addiction, as the brain starts to crave these pleasurable effects and may seek them out repeatedly.

Better Relief 

Throughout history, humans have sought to relieve pain; aspirin dates back 3500 years, and opium even longer. As we grapple with aging populations and ever-evolving diseases, healthcare professionals, researchers, and students alike will have to research, develop, and understand as many analgesics as possible.