First, what are NSAIDs?
NSAIDs stands for “nonsteroidal anti-inflammatory drugs.” NSAIDs include over-the-counter drugs such as Ibuprofen and prescription drugs such as Voltaren. They reduce inflammation by inhibiting enzymes named cyclooxygenase (COX) enzymes. These enzymes play an important role in converting arachidonic acid into prostaglandins, which are lipids that are usually released at sites of injury or infection. Prostaglandins promote inflammation which leads to dilation of blood vessels and exit of immune cells from the bloodstream into the wound site to promote repair. Inflammation is the redness and swelling that you see when you cut your skin for example. This can also lead to the development of a fever.
So, NSAIDs lessen inflammation, but how does that reduce pain perception?
To answer this question, we must first recognize that inflammation plays an important role in the genesis and persistence of pain after injury. During inflammation, immune cells flood the site of injury, where they release factors, such as cytokines, that make cells of the nervous system that transmit information about potentially painful information more sensitive. These cells are neurons called nociceptors. They carry information about potentially damaging stimuli from the injury site to the spinal cord. By making nociceptors more sensitive, inflammation enhances pain perception. Even a light touch, which normally wouldn’t lead to pain, because those nociceptors are more sensitive, will now cause pain. NSAIDs calm down the inflammation, and in doing so immune cells can no longer sensitize those nociceptors, returning pain levels to baseline.
This figure shows the mechanism by which NSAIDs block neuropathic pain. NSAIDs inhibit COX enzymes' ability to convert arachidonic acid into prostaglandins. By doing so, NSAIDs dampen inflammation and pain perception.
Since NSAIDs treat inflammation, there are certain types of pain, such as neuropathic pain, that NSAIDs can't relieve. Neuropathic pain is pain due to infection or injury to cells of the nervous system.
How is that different than opioids?
Opioids work directly to neurons in the brain, spinal cord, and the periphery. (For more on opioids see: How do opioids work?) There are many downsides to opioids, most notably addiction. Long term opioid use can also lead to depression, nausea, and potentially even increased pain sensitivity.
NSAIDs work on the inflammation at the injury site, while opioids work directly on nociceptors and other neurons in the central nervous system. Moreover, NSAIDs can be found over-the-counter, while opioids require a prescription.
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