An itch we can't scratch ... yet
or technically,
TRPC3 Is Dispensable for β-Alanine Triggered Acute Itch.
[See Original Abstract on Pubmed]
Authors of the study: Peter Dong, Changxiong Guo, Shengxiang Huang, Minghong Ma, Qin Liu & Wenqin Luo
You’re sitting peacefully on your couch and all of a sudden your nose itches. Annoying, right? Why does this happen? More importantly, how can our bodies sense this itch in the first place? This “itch” sensation, also known as pruritoception, has evolved in humans and other animals as an important alarm system for possible threats. These include anything from small microbes to poisons/toxins that can come from plants, food, and even some medications. Although we know that this sensation exists, neuroscientists don’t know much about how the cells in our brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. (neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles) sense itch in the first place.
The skin is the largest organ of the human body, and within it lie many different sensors for detecting stimuli from the outside world. One class of these sensors - called nociceptors - send information to the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. about pain, temperature, and, you guessed it, itch. One important nociceptor for itch is called the “Mas-related G-proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. coupled receptorReceives an input some stimulus and transmits a the information to other cells or neurons. member D” (yikes!), we’ll call that the MRGPRD receptorReceives an input some stimulus and transmits a the information to other cells or neurons. from now on. The reason it’s important for itch is because it detects the itch-inducing chemical, 𝛽-alanine. MRGPRD is broadly expressed, which just means scientists find a lot of this receptorReceives an input some stimulus and transmits a the information to other cells or neurons. in certain parts of the spinal cord. The spinal cord is an organ that is really important for touch and itch because it allows the body to communicate with the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. However, in order for information from organs such as the skin to reach the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals., it needs specific “decoder proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies.” that will convert this initial information at the level of the spinal cord into a format the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. will understand. You can think of these decoder proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. as being analogous to Google Translate. If you’re visiting a foreign country and need to translate a word you’ve read, you can use your Google Translate app to translate it into English, a language you understand. However, scientists don’t really know which proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. are functioning as decoders to convert the information the MRGPRD detects to the kind of information that the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. can understand. Peter Dong, a neuroscience graduate student working with Dr. Wenqin Luo at UPenn, set out to try to address this question in his research.
One family of “decoder proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies.” that have been shown to play a role in the detection of many senses such as temperature, pressure, and pain is known as the “transient receptorReceives an input some stimulus and transmits a the information to other cells or neurons. potential” (TRP, pronounced “trip”) family. However, the exact role of TRP proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. in decoding itch sensations remains uncertain. Peter chose to test one proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. in this family, called TRPC3, to determine whether or not it was the “translator” of information being detected by MRGPRD. Why TRPC3? Well, TRPC3 has been shown to respond to touch sensation, and in Peter’s study, the data showed that TRPC3 is present in the same neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles that contain MRGPRD. The next question Peter wanted to ask was whether MRGPRD-containing cells needed TRPC3 in the spinal cord in order to properly translate their messages for the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. So he studied a mouse that did not have any TRPC3 proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. anywhere in its body, including the spinal cord. We’ll call this the TRPC3 “knockout” mouse. Peter found that even in mice without TRPC3, MRGPRD was still present. This suggests that TRPC3 is not needed for normal MRGPRD presence and functioning.
So what does this mean? Is TRPC3 the proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. converting itch signals from MRGPRD to the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. or not? Peter and his colleagues addressed this question by doing behavioral studies on their TRPC3 knockout mice. They injected 𝛽-alanine (the itch-inducing chemical) into the back or cheek of mice lacking TRPC3 proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies., and then measured how much they scratched to test if TRPC3 is required for itch sensation. They found that normal mice and TRPC3 knockout mice both still scratched a lot. This suggests that TRPC3 alone is not needed for itch, because the mice lacking TRPC3 were still very itchy.
Though Peter wanted to scratch his itch of knowing which proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. translates sensory information from MRGPRD to the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals., TRPC3 is not it. Although he was a little disappointed, this is actually a really good thing to know! This finding will give insight to researchers that can try to study other types of proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. in the TRP family as well as additional groups of proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. families! This research not only helps us understand why and how humans evolved to detect itch, but it also provides a stepping stone for the development of treatments for patients who suffer chronic itch as a symptom of diseases such as multiple sclerosis, neuropathy or shingles. Currently there are no good medications to relieve chronic itch, therefore, knowing more about how we detect itch at a molecular level will help scientists develop medications to improve the quality of life of these patients.
The skin is the largest organ of the human body, and within it lie many different sensors for detecting stimuli from the outside world. One class of these sensors - called nociceptors - send information to the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. about pain, temperature, and, you guessed it, itch. One important nociceptor for itch is called the “Mas-related G-proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. coupled receptorReceives an input some stimulus and transmits a the information to other cells or neurons. member D” (yikes!), we’ll call that the MRGPRD receptorReceives an input some stimulus and transmits a the information to other cells or neurons. from now on. The reason it’s important for itch is because it detects the itch-inducing chemical, 𝛽-alanine. MRGPRD is broadly expressed, which just means scientists find a lot of this receptorReceives an input some stimulus and transmits a the information to other cells or neurons. in certain parts of the spinal cord. The spinal cord is an organ that is really important for touch and itch because it allows the body to communicate with the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. However, in order for information from organs such as the skin to reach the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals., it needs specific “decoder proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies.” that will convert this initial information at the level of the spinal cord into a format the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. will understand. You can think of these decoder proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. as being analogous to Google Translate. If you’re visiting a foreign country and need to translate a word you’ve read, you can use your Google Translate app to translate it into English, a language you understand. However, scientists don’t really know which proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. are functioning as decoders to convert the information the MRGPRD detects to the kind of information that the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. can understand. Peter Dong, a neuroscience graduate student working with Dr. Wenqin Luo at UPenn, set out to try to address this question in his research.
One family of “decoder proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies.” that have been shown to play a role in the detection of many senses such as temperature, pressure, and pain is known as the “transient receptorReceives an input some stimulus and transmits a the information to other cells or neurons. potential” (TRP, pronounced “trip”) family. However, the exact role of TRP proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. in decoding itch sensations remains uncertain. Peter chose to test one proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. in this family, called TRPC3, to determine whether or not it was the “translator” of information being detected by MRGPRD. Why TRPC3? Well, TRPC3 has been shown to respond to touch sensation, and in Peter’s study, the data showed that TRPC3 is present in the same neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles that contain MRGPRD. The next question Peter wanted to ask was whether MRGPRD-containing cells needed TRPC3 in the spinal cord in order to properly translate their messages for the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. So he studied a mouse that did not have any TRPC3 proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. anywhere in its body, including the spinal cord. We’ll call this the TRPC3 “knockout” mouse. Peter found that even in mice without TRPC3, MRGPRD was still present. This suggests that TRPC3 is not needed for normal MRGPRD presence and functioning.
So what does this mean? Is TRPC3 the proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. converting itch signals from MRGPRD to the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. or not? Peter and his colleagues addressed this question by doing behavioral studies on their TRPC3 knockout mice. They injected 𝛽-alanine (the itch-inducing chemical) into the back or cheek of mice lacking TRPC3 proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies., and then measured how much they scratched to test if TRPC3 is required for itch sensation. They found that normal mice and TRPC3 knockout mice both still scratched a lot. This suggests that TRPC3 alone is not needed for itch, because the mice lacking TRPC3 were still very itchy.
Though Peter wanted to scratch his itch of knowing which proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. translates sensory information from MRGPRD to the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals., TRPC3 is not it. Although he was a little disappointed, this is actually a really good thing to know! This finding will give insight to researchers that can try to study other types of proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. in the TRP family as well as additional groups of proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. families! This research not only helps us understand why and how humans evolved to detect itch, but it also provides a stepping stone for the development of treatments for patients who suffer chronic itch as a symptom of diseases such as multiple sclerosis, neuropathy or shingles. Currently there are no good medications to relieve chronic itch, therefore, knowing more about how we detect itch at a molecular level will help scientists develop medications to improve the quality of life of these patients.
About the brief writer: Solymar Rolon
Solymar is a PhD Candidate in Maria Geffen’s lab. She is studying the role of amygdala-thalamic projections in auditory behavior.