How do painkillers actually kill pain?

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, 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.

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. Over-the-counter medications are generally safe if the directions on the bottle are followed strictly.

Corticosteroids like 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.

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.

Nerve injuries, most commonly from arthritis and diabetes, can cause the pain-sensing part of the nervous system to become overactive. These injuries sound the pain alarm even in the absence of tissue damage. The best painkillers in these conditions are those that dampen that alarm.

Antiepileptic drugs, such as gabapentin (Neurontin), suppress the pain-sensing system by blocking electrical signaling in the nerves. However, gabapentin can also reduce nerve activity in other parts of the nervous system, potentially leading to sleepiness and confusion.

Antidepressants, such as duloxetine and nortriptyline, are thought to work by increasing certain neurotransmitters in the spinal cord and brain involved in regulating pain pathways. But they may also alter chemical signalling in the gastrointestinal tract, leading to an upset stomach.

Opioids decrease pain by activating the body’s endorphin system. Endorphins are a type of opioid your body naturally produces that decreases incoming signals of injury and produces feelings of euphoria – the so-called “runner’s high.” Opioids simulate the effects of endorphins.

Although opioids can decrease some types of acute pain, such as after surgery, musculoskeletal injuries like a broken leg or cancer pain, they are often ineffective for neuropathic injuries and chronic pain.

Because the body uses opioid receptors in other organ systems like the gastrointestinal tract and the lungs, side effects and risks include constipation and potentially fatal suppression of breathing. All opioids are controlled substances and are carefully prescribed by doctors because of these side effects and risks.

Although cannabis has received a lot of attention for its potential medical uses, there isn’t sufficient evidence available to conclude that it can effectively treat pain. Since the use of cannabis is illegal at the federal level in the U.S., high-quality clinical research funded by the federal government has been lacking.

Researchers do know that the body naturally produces endocannabinoids, a form of the chemicals in cannabis, to decrease pain perception. Cannabinoids may also reduce inflammation.

While sounding the pain alarm is important for survival, dampening the klaxon when it’s too loud or unhelpful is sometimes necessary.

No existing medication can perfectly treat pain. Matching specific types of pain to drugs that target specific pathways can improve pain relief, but even then, medications can fail to work even for people with the same condition. More research that deepens the medical field’s understanding of the pain pathways and targets in the body can help lead to more effective treatments and improved pain management.