How do painkillers kill pain? It’s about meeting the pain where it is

A variety of pain-relieving medications are available both over the counter and by prescription.
enlarge A variety of pain-relieving medications are available both over the counter and by prescription.

Without the ability to feel pain, life is more dangerous. To avoid injury, the pain tells us to use a hammer more gently, wait for the soup to cool, or put on gloves in a snowball fight. Those with rare hereditary conditions that prevent them from feeling pain are unable to protect themselves from environmental threats, leading to broken bones, damaged skin, infections and ultimately a shorter lifespan.

In this context, pain is much more than a sensation: it is a protective call to action. But pain that is too intense or prolonged can be debilitating. So how does modern medicine soften the call?

As a neurobiologist and anesthesiologist who studies pain, this is a question we and other researchers have been trying to answer. Science’s understanding of how the body perceives tissue damage and perceives it as pain has grown tremendously in recent years. It has become clear that there are multiple pathways that signal tissue damage to the brain and sound the pain alarm bell.

Interestingly, although the brain uses different pain signaling pathways depending on the type of damage, there is also redundancy for these pathways. Even more intriguing, these neural pathways alter and amplify signals in the case of chronic pain and pain caused by conditions that affect the nerves themselves, although the protective function of pain is no longer necessary.

Pain relievers work by targeting different parts of these pathways. However, not every pain reliever works for every type of pain. Due to the multiplicity and redundancy of pain pathways, a perfect pain reliever is elusive. But in the meantime, understanding how existing pain relievers work helps healthcare providers and patients use them for the best results.

Anti-Inflammatory Painkillers

A bruise, sprain, or broken bone from 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.

Commonly used over-the-counter anti-inflammatory pain relievers work by reducing 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 such as ibuprofen (Advil, 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 reduces the amount of inflammatory chemicals and therefore reduces the pain signals sent to the brain. While acetaminophen (Tylenol), also known as acetaminophen, doesn’t reduce inflammation the way NSAIDs do, it also inhibits COX enzymes and has similar pain-reducing effects.

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

Because inflammatory chemicals are involved in important physiological functions other than just setting off the pain alarm, drugs that block them will have side effects and potential health risks, including irritation of the stomach lining and impairing kidney function. Over-the-counter medications are generally safe if the directions on the bottle are strictly followed.

Corticosteroids like prednisone block the inflammatory cascade early on in the process, which is probably why they are so powerful at reducing inflammation. However, because all the chemicals in the cascade are present in almost every organ system, long-term steroid use can pose many health risks that should be discussed with a doctor before starting a treatment plan.

topical medication

Many topical medications target nociceptors, the specialized nerves that detect tissue damage. Local anesthetics, such as 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 pain relievers. Activating these proteins can induce certain sensations that can reduce pain by reducing the activity of damage-sensitive nerves, such as the cooling sensation of menthol or the burning sensation of capsaicin.

Certain topical ointments, such as menthol and capsaicin, can displace pain signals with different sensations.
enlarge Certain topical ointments, such as menthol and capsaicin, can displace pain signals with different sensations.

Because these topical medications work on the small nerves in the skin, they are best used for pain that directly affects the skin. For example, a shingles infection can damage nerves in the skin, making them overactive and sending persistent pain signals to the brain. Silencing those nerves with topical lidocaine or an overwhelming dose of capsaicin can reduce these pain signals.

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