Itching is an unpleasant sensation associated with the desire to scratch, and the itch sensation is an important protective mechanism for animals. However, chronic itch, often seen in patients with skin and liver diseases, remains a challenging clinical problem as uncontrollable scratching causes severe skin and tissue damage.
Therapeutic approaches for chronic itch treatment have developed slowly due to the lack of knowledge about itch mechanisms.
A recent study carried out by Dr. Sun Yangang鈥檚 lab at the Institute of Neuroscience of the Chinese Academy of Sciences discovered a central neural circuit that is critical for transmitting the itch signal.
The researchers first investigated how the spinal itch-specific neurons send itch signals to the brain. Spinal neurons expressing gastrin-releasing peptide receptor (GRPR) have been shown to be crucial for itch signal processing. They found that the spinal GRPR neurons did not send the itch signal directly to the brain. Since the PBN is activated during itch processing, they postulated that the spinal GRPR neurons might be connected to the PBN poly-synaptically, and thus send itch information to the PBN indirectly.
To test this hypothesis, researchers constructed a transgenic mouse line and selectively expressed light-sensitive channels in GRPR neurons. Light-induced activation of the spinal GRPR neurons evoked excitatory postsynaptic responses in the spinal neurons that project to the PBN. This result demonstrated that spinal GRPR neurons activate the PBN via connection to the projection neurons, supporting their idea.
The researchers also examined whether the spino-parabrachial pathway plays a functional role in itch processing. By manipulating the spino-parabrachial pathway with optogenetics, they showed that inhibition of the spino-parabrachial pathway suppressed itch-induced scratching behavior.
In addition, researchers confirmed the functional role of PBN in itch processing. They showed that the activity of PBN neurons was elevated during itch processing. At the behavioral level, suppression of the activity of PBN neurons also reduced scratching behavior, suggesting that PBN plays a key role in itch processing.
This study paves the way for further dissection of central circuit mechanisms underlying itch signal processing, and provides a potential target for therapeutic treatment of chronic itching. The study was published in Science.
Source: CAS; edited by APBN
Click here for the complete issue.