Feeling the itch
28 Nov 2011 by Evoluted New Media
Itching is the most common side-effects of morphine, and scientists in America may have discovered a way to supress the medication’s itch without affecting its pain-killing properties. Researchers from Washington University’s Centre for the Study of Itch team identified and blocked a specific variant of the opioid receptor – MOR1D – in the spinal cord of mice that inhibits the itch without altering the drug’s pain-killing properties. The discovery could produce new treatments to eliminate itching in cancer and surgery patients, and women receiving an epidural during labour.
MOR1D induced itching in mice on morphine by activating GRPR or gastrin-releasing peptide receptor, an itch-specific receptor previously discovered by research leader Zhou-Feng Chen. When MOR1D was blocked, mice receiving morphine resisted itching, but still received the same level of pain relief.
“It is exciting to know that MOR1D actually functions as an itch-specific receptor,” Chen said. “Depending on different types of itch-producing substances, our study suggests that the body has different ways of activating GRPR to transmit itch. In this case, opioids such as morphine first activate MOR1D, and that receptor subsequently connects to GRPR to relay itch signals.”
Postdoctoral researcher Xian-Yu Liu also discovered that MOR1 – a major variant of the receptor – exclusively mediates morphine’s analgesic effects in the spinal cord. When MOR1D was blocked, the mice stopped itching, but when MOR1 was blocked, the mice received no pain-killing benefits, but still continued to itch.
“Scientists have blamed the wrong receptor, but now the culprit has been caught,” said Chen. “There are more than a dozen forms of the opioid receptor on nerve cells, but MOR1D is the first one that has nothing to do with killing pain. It only transmits itch.”
MOR1D and MOR1 are identical, except for seven amino acids found in MOR1D – Chen says these are critical for the interaction between MOR1D and GRPR in the spinal cord.
“They operate like a key that can be used to open a door. Without the key, MOR1 can’t activate GRPR even though the receptor is activated by morphine.”
He hopes that by altering the key, the itch could be eliminated without destroying the receptors, as they may have other important functions not related to itching.
Chen suspects that other variants of the receptor may be related to other common side-effects of like nausea, respiratory depression and constipation. He hopes his research will motivate others to study these receptors and their effects.
Unidirectional cross-activation of GRPR by MOR1D uncouples itch and analgesia induced by opioids
