Millions of patients benefit from opioids such as morphine and codeine, but the pain relief they provide often comes with intense itching. In some cases, the irritation is so bad that patients will opt to cut back on painkillers. Now a study in the October 14 issue of Cell has found a possible explanation—the first step to creating drugs that will not make patients choose between experiencing itchiness and pain.

Until recently, many experts had assumed that itching from opioids was unavoidable because it is a common side effect of drugs that interact with the nervous system. The brain has four main types of receptors that respond to opioids, and every type has many structural variants, called isoforms. Most opioids are nonspecific, which means they bind to all the isoforms. This leads to powerful pain relief, although scientists do not know exactly why.

In the new research, a team led by itch researcher Zhou-Feng Chen of Washington University in St. Louis showed that only one opioid receptor isoform is responsible for itching—and it is not involved in pain. Mice bred to have fewer of these particular receptors did not scratch themselves when given an opioid, but they did exhibit the telltale mouse signs of pain relief, such as less flinching when researchers flicked their tails.

Now that scientists know that pain relief and itching can be decoupled, they will try to make itch-free opioid drugs a reality.

This article was published in print as "Defeating Pain without the Itch."