Reducing pain with morphine

Even after decades of researching painkillers, morphine still remains one of the most effective drugs against pain. Most painkillers have an upper threshold – at a certain point, they are ineffective. However, morphine is able to block more and more pain with increasing doses. Morphine does have side effects, though, from minor ones such as nausea and constipation to life-threatening side effects of respiratory depression. Though far from perfect, morphine is still considered the most valuable painkiller in contemporary medicine.

Though we have always known morphine to be extremely effective, its mechanism of action has evaded scientists for a long time. We now know that morphine is so effective because it acts directly on opioid receptors, a type of g-protein coupled receptor (GPCR) that modulates pain in our nervous system. Opioid receptors are distributed widely in the brain, and can be found in our spinal cord and digestive tract. These receptors are known to respond to compounds such as encephalin, built by our own bodies to control pain. For example, during exercise, endorphins are produced which can reduce pain levels during strenuous activity. Morphine can mimic these compounds and artificially block pain messages.

When morphine binds to opioid receptors, it activates a series of events in which the GPCR activates its corresponding g-protein and triggers an increased conduction through potassium channels, decreased conduction through calcium channels, and an inhibition of adenylyl cyclase, also known as adenylate cyclase. Together, these changes in our nervous system reduce the effect of our body’s signaling systems that transmit pain.