From Ibuprofen to Fentanyl: How Do Painkillers Actually Kill Pain?

While pain can be horrible, it serves a useful purpose. Without the ability to feel pain, life is more dangerous. To avoid injury, pain tells us to swing a hammer more gently, wait for the soup to cool down, or put on gloves in a snowball fight. People with rare inherited disorders that leave them without the ability to feel pain are unable to protect themselves from environmental threats, leading to broken bones, damaged skin, infections, and ultimately a shorter life span.

Pain is much more than a sensation in these contexts: It is a protective call to action. However, pain that is too intense or long-lasting can be debilitating. So how does modern medicine soften the call?

As a neurobiologist and an anesthesiologist who study pain, this is a question we and other researchers have tried to answer. Science’s knowledge of how the body senses tissue damage and perceives it as pain has progressed tremendously over the past several years. It has now become clear that there are multiple pathways that signal tissue damage to the brain and sound the pain alarm bell.

Interestingly, while the brain employs distinct pain signaling pathways depending on the type of damage, there is also redundancy to these pathways. Even more intriguing, these neural pathways morph and amplify signals in the case of chronic pain and pain caused by conditions affecting nerves themselves, even though the protective function of pain is no longer required.

Painkillers work by tackling different parts of these pathways. Not every pain reliever works for every type of pain, however. Because of the multitude and redundancy of pain pathways, a perfect painkiller is elusive. But in the meantime, understanding how existing pain relievers work helps medical providers and patients use them for the best results.

Anti-inflammatory painkillers

A bruise, sprain, or broken bone from an injury all lead to tissue inflammation, an immune response that can lead to swelling and redness as the body tries to heal. Specialized nerve cells in the area of the injury called nociceptors sense the inflammatory chemicals the body produces and send pain signals to the brain.

Common over-the-counter anti-inflammatory painkillers work by decreasing inflammation in the injured area. These are particularly useful for musculoskeletal injuries or other pain problems caused by inflammation such as arthritis.

Nonsteroidal anti-inflammatories like ibuprofen (Advil and Motrin), naproxen (Aleve), and aspirin do this by blocking an enzyme called COX that plays a key role in a biochemical cascade that produces inflammatory chemicals. Blocking the cascade decreases the amount of inflammatory chemicals, and thereby reduces the pain signals sent to the brain. While acetaminophen (Tylenol), also known as paracetamol, doesn’t reduce inflammation as NSAIDs do, it also inhibits COX enzymes and has similar pain-reducing effects.

Prescription anti-inflammatory painkillers include other COX inhibitors, corticosteroids and, more recently, drugs that target and inactivate the inflammatory chemicals themselves.

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Aspirin and ibuprofen work by blocking the COX enzymes that play a key role in pain-causing processes.

Because inflammatory chemicals are involved in other important physiological functions beyond just sounding the pain alarm, medications that block them will have side effects and potential health risks, including irritating the stomach lining and affecting kidney function. Fortunately, over-the-counter medications are generally safe if the directions on the bottle are followed strictly.

Corticosteroids such as prednisone block the inflammatory cascade early on in the process, which is probably why they are so potent in reducing inflammation. However, because all the chemicals in the cascade are present in nearly every organ system, long-term use of steroids can pose many health risks that need to be discussed with a physician before starting a treatment plan.

Topical medications

Many topical medications target nociceptors, the specialized nerves that detect tissue damage. Local anesthetics, like lidocaine, prevent these nerves from sending electrical signals to the brain.

The protein sensors on the tips of other sensory neurons in the skin are also targets for topical painkillers. Activating these proteins can elicit particular sensations that can lessen the pain by reducing the activity of the damage-sensing nerves, like the cooling sensation of menthol or the burning sensation of capsaicin.

Source: SciTechDaily