Outstanding Chinese scholar's latest Cell article analyzes itching
Dr. Chen Zhoufeng, who graduated from Wuhan University in the early years, pioneered a new generation of itching neurology research. In the Nature and Science articles published in 2007 and 2009, respectively, he discovered the first central nervous system itching gene to distinguish itching from pain. Here, a long-standing dispute in this field has been resolved. Recently, his research group has made important new discoveries in this research field, revealing the molecular mechanism of why morphine used for pain relief can cause itching. The research results were published in Cell magazine.
The most common side effect of using narcotic drugs such as morphine is itching. For many years, scientists have hoped to understand why these drugs used for pain relief cause itching, but so far there has not been a good explanation.
In this article, Dr. Chen Zhoufeng and his colleagues at the University of Washington have discovered ways to regulate opioid-induced itching without affecting the effectiveness of drugs to reduce pain. This discovery will help develop new treatments to reduce cancer and itching caused by surgery.
Dr. Chen Zhoufeng identified the first itch-sensing gene in the central nervous system in 2007, which provided a target for the development of anti-itch drugs. This "itch gene" is called GRPR (gastrin-releasing peptide receptor), and its encoded receptor protein is only present in a few spinal cords that deliver pain and itching signals from the skin to the brain. Nerve cells. The research team led by Dr. Chen Zhoufeng found that laboratory mice lacking this gene itched less frequently than normal mice in the same cage when given itching stimulation. Laboratory research results confirmed the relationship between GRPR and itch perception. For the first time, itch perception has specific receptors in the central nervous system.
Later, the research team discovered a group of neurons in the mice that responded to itching stimuli. The reorganized neurons will inform the brain that it is time to start scratching. The findings themselves have scratched a long-term itch in neuroscience: whether the nervous system handles pain and itching in the same way. Researchers have debated whether itching is basically just a form of pain or whether there are specialized itch, pain, and other sensations in the body (the so-called "marked line hypothesis") neural pathways.
To further understand the function of GRPR-expressing nerve cells, Dr. Chen Zhoufeng's research group selectively killed and eliminated GRPR-expressing cells in the spinal cord of mice. It turns out that no matter how strong itching substance you inject, mice without GRPR neurons will basically not scratch. Most surprisingly, these mice responded normally to acute pain, chronic pain, mechanical pain, chemical pain, and heat pain, so this study demonstrated for the first time that GRPR-expressing cells are specifically responsible for delivery Itchy nerve cells. Unlike previous studies, this study provides very complete behavioral evidence for measuring itching and pain to support the presence of itching cells.
Original summary:
Unidirectional Cross-Activation of GRPR by MOR1D Uncouples Itch and Analgesia Induced by Opioids
Spinal opioid-induced itch, a prevalent side effect of pain management, has been proposed to result from pain inhibition. We now report that the -opioid receptor (MOR) isoform MOR1D is essential for morphine-induced scratching (MIS), whereas the isoform MOR1 is required only for morphine-induced analgesia (MIA). MOR1D heterodimerizes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, relaying itch information. We show that morphine triggers internalization of both GRPR and MOR1D, whereas GRP specifically triggers GRPR internalization and morphine-independent scratching. Providing potential insight into opioid-induced itch prevention, we demonstrate that molecular and pharmacologic inhibition of PLCβ3 and IP3R3, downstream effectors of GRPR, specifically block MIS but not MIA. In addition, blocking MOR1D-GRPR association attenuates MIS but not MIA. Together, these data suggest that opioid-induced itch is an active process concomitant with but independent of opioid analg esia, occurring via the unidirectional cross-activation of GRPR signaling by MOR1D heterodimerization.
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