BRAINS IN BRIEFS
Scroll down to see new briefs about recent scientific publications by neuroscience graduate students at the University of Pennsylvania. Or search for your interests by key terms below (i.e. sleep, Alzheimer’s, autism).
Shedding light on migraines: Signals from the eye make people with migraine more sensitive to light
or technically,
Selective amplification of ipRGC signals accounts for interictal photophobia in migraine
[See Original Abstract on Pubmed]
or technically,
Selective amplification of ipRGC signals accounts for interictal photophobia in migraine
[See Original Abstract on Pubmed]
Authors of the study: Harrison McAdams, Eric A Kaiser, Aleksandra Igdalova, Edda B Haggerty, Brett Cucchiara, David H Brainard, Geoffrey K Aguirre
Have you ever stepped outside and had to squint or shield your eyes from the sun? Bright light can be uncomfortable for anyone, but it can be especially painful to those who experience migraines. While headaches are often associated with migraines, another common symptom is photophobia, or sensitivity to light. Harrison McAdams, a neuroscience student in Dr. Geoffrey Aguirre‘s lab
at Penn, wanted to find out what part of the eye or brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. might be responsible for the symptom of photophobia in migraines.
In order to discover how photophobia might arise, we need to understand how our eyes allow us to see our surroundings. The first step in vision is when light hits the retina, a sheet of cells that covers the back of the eye. The retina is made of three layers of neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles with specific functions. Some of these neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles can detect light: these are the rods and cones, and they become excited by photons, the particles that make up light. Rods work in dim light, while cones work in bright light and can sense red, green, or blue light. This is how we’re able to see in color! Rods and cones talk to other neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles in the retina like RGCs (retinal ganglion cells), which then send signals out of the eye and to many different areas of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals..
In order to discover how photophobia might arise, we need to understand how our eyes allow us to see our surroundings. The first step in vision is when light hits the retina, a sheet of cells that covers the back of the eye. The retina is made of three layers of neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles with specific functions. Some of these neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles can detect light: these are the rods and cones, and they become excited by photons, the particles that make up light. Rods work in dim light, while cones work in bright light and can sense red, green, or blue light. This is how we’re able to see in color! Rods and cones talk to other neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles in the retina like RGCs (retinal ganglion cells), which then send signals out of the eye and to many different areas of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals..
Most RGCs just listen to the rods and cones that talk to them; however, there are special RGCs that are “intrinsically photosensitive” (ipRGCs), which means they can detect light just like rods and cones do. These ipRGCs actually don’t help you see images. Instead, they are responsible for your sense of a day/night cycle and for helping your pupils adjust to the light or dark. There is also evidence that ipRGCs connect to the thalamus, an area of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. which can sense pain. Harrison thought this connection could explain why light can be especially painful to people with migraine.
60 people participated in this study: 40 experienced photophobia from migraines and 20 did not have migraines for comparison. Pulses of different colored light were flashed in one eye to either activate the cones, the ipRGCs, or both. They rated how painful each flash of light was on a scale from 0 to 10, 10 being the most painful. People with photophobia tended to rate the “cone” light as more painful compared to those without, and their rating increased as the light got brighter. Since we know that they’re sensitive to bright light and that cones work in bright light, this makes sense. Interestingly, they also gave higher pain ratings to light which only activated the ipRGCs.
From this test, Harrison knew that ipRGC activity could cause pain. After recording pupil size while the light was flashing, he found no difference in people with or without migraine. This means that not all ipRGC functions are affected: It’s a specific strengthening of the signal from the retina to the pain-sensing area of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals..
Why would our eyes be wired like this? Just like touching a hot stove can damage your hand, staring at the sun or shining a flashlight in your eyes can damage your retinas. And once those neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles are gone, they’re gone for good--so take care of them! Although this signal can be helpful, warning us that what we’re doing is harmful, it seems like when the signal becomes too strong, people can develop migraines. Identifying the root of the problem is the first step in developing treatments to help people who live with this condition.
60 people participated in this study: 40 experienced photophobia from migraines and 20 did not have migraines for comparison. Pulses of different colored light were flashed in one eye to either activate the cones, the ipRGCs, or both. They rated how painful each flash of light was on a scale from 0 to 10, 10 being the most painful. People with photophobia tended to rate the “cone” light as more painful compared to those without, and their rating increased as the light got brighter. Since we know that they’re sensitive to bright light and that cones work in bright light, this makes sense. Interestingly, they also gave higher pain ratings to light which only activated the ipRGCs.
From this test, Harrison knew that ipRGC activity could cause pain. After recording pupil size while the light was flashing, he found no difference in people with or without migraine. This means that not all ipRGC functions are affected: It’s a specific strengthening of the signal from the retina to the pain-sensing area of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals..
Why would our eyes be wired like this? Just like touching a hot stove can damage your hand, staring at the sun or shining a flashlight in your eyes can damage your retinas. And once those neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles are gone, they’re gone for good--so take care of them! Although this signal can be helpful, warning us that what we’re doing is harmful, it seems like when the signal becomes too strong, people can develop migraines. Identifying the root of the problem is the first step in developing treatments to help people who live with this condition.
About the brief writer: Sierra Foshe
Sierra is a PhD student in Josh Dunaief's lab. She is interested in the mechanisms of retinal inflammation and degeneration.
Want to learn more about the role of ipRGCs in photophobia? You can find Harrison’s full paper here!
My back hurts, my hand hurts: is pain different in different parts of the body?
or technically,
Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.
[See Original Abstract on Pubmed]
or technically,
Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.
[See Original Abstract on Pubmed]
Authors of the study: William Olson, Ishmail Abdus-Saboor, Lian Cui, Justin Burdge, Tobias Raabe, Minghong Ma, Wenqin Luo
Have you ever wondered why you can feel the details of an object with your fingertips, but not with your elbow? Your body detects sensations including touch and pain using specialized nerves that detect information in your environment and transmit it to your brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. Together, these nerves are called the “sensory system.” As you may have noticed, however, this system does not treat all body regions the same. This is why your fingertips are much more sensitive to touch stimuli than other parts of your body (imagine trying to feel Braille with the back of your hand). Our fingertips are very sensitive to touch mainly because they contain more ‘touch-sensitive’ nerve endings than other body regions.
Pain perception relies on ‘pain-sensitive’ nerve endings that are distinct from our ‘touch-sensitive’ nerve endings. But just like for touch, certain regions of our body, like our fingertips, are more sensitive to pain than others. Interestingly, unlike for touch, this is not because we have more ‘pain-sensitive’ nerve endings in pain-sensitive areas. In fact, we have relatively few ‘pain-sensitive’ nerve endings in our fingertips -- even though they are extremely sensitive to pain! This observation surprised Will Olson, a neuroscience graduate student in Wenqin Luo’s lab. He wondered how certain parts of the body are more sensitive to pain than others.
To figure this out, he carefully studied the shape and size of pain nerve endings in mice. These nerves are like wires that run all the way from your skin into your spinal cord. This means there are two endings of these nerves: one in the skin and one in the spinal cord. Will took a good look at both ends. He saw that, in general, ‘pain-sensitive’ nerves come in different shapes and sizes depending on where in the body they are found. Interestingly, he found that pain nerve endings have a low density in the mouse paw, just like in the human hand! The pain nerve endings in the paw also looked very similar to pain nerve endings in other parts of the mouse. This surprised Will because he knew that mice have very high pain sensitivity in their paws. He wondered, if the density and the shape of the pain nerves in the paw skin is the same as in other parts of the body, then why are paws so sensitive to pain?! The answer became clear when Will looked at these nerves in the spinal cord -- in the spinal cord, paw pain nerves look completely different from pain nerves that come from other parts of the mouse. Will hypothesized that the special shape of these paw pain nerves could enhance pain sensation in the paw. And in fact, Will found that these paw pain nerves are better at sending information to the spinal cord than pain nerves that come from other parts of the mouse.
While these findings are interesting and could even help some of us decide on the least painful place to get a tattoo, this study might also help people with chronic pain. Chronic pain occurs when people feel pain for weeks, months or even years. Based on this study, we may be able to identify specific causes of chronic pain in different parts of the body. For example, chronic back pain might be very different from chronic joint pain. Our current pain medications are not effective as treatments for many forms of chronic pain. The lack of good treatments has contributed to the increase in opioid prescriptions that led to opioid addiction crisis. Identifying more specific causes of chronic pain could give researchers ideas for better ways to treat it.
Pain perception relies on ‘pain-sensitive’ nerve endings that are distinct from our ‘touch-sensitive’ nerve endings. But just like for touch, certain regions of our body, like our fingertips, are more sensitive to pain than others. Interestingly, unlike for touch, this is not because we have more ‘pain-sensitive’ nerve endings in pain-sensitive areas. In fact, we have relatively few ‘pain-sensitive’ nerve endings in our fingertips -- even though they are extremely sensitive to pain! This observation surprised Will Olson, a neuroscience graduate student in Wenqin Luo’s lab. He wondered how certain parts of the body are more sensitive to pain than others.
To figure this out, he carefully studied the shape and size of pain nerve endings in mice. These nerves are like wires that run all the way from your skin into your spinal cord. This means there are two endings of these nerves: one in the skin and one in the spinal cord. Will took a good look at both ends. He saw that, in general, ‘pain-sensitive’ nerves come in different shapes and sizes depending on where in the body they are found. Interestingly, he found that pain nerve endings have a low density in the mouse paw, just like in the human hand! The pain nerve endings in the paw also looked very similar to pain nerve endings in other parts of the mouse. This surprised Will because he knew that mice have very high pain sensitivity in their paws. He wondered, if the density and the shape of the pain nerves in the paw skin is the same as in other parts of the body, then why are paws so sensitive to pain?! The answer became clear when Will looked at these nerves in the spinal cord -- in the spinal cord, paw pain nerves look completely different from pain nerves that come from other parts of the mouse. Will hypothesized that the special shape of these paw pain nerves could enhance pain sensation in the paw. And in fact, Will found that these paw pain nerves are better at sending information to the spinal cord than pain nerves that come from other parts of the mouse.
While these findings are interesting and could even help some of us decide on the least painful place to get a tattoo, this study might also help people with chronic pain. Chronic pain occurs when people feel pain for weeks, months or even years. Based on this study, we may be able to identify specific causes of chronic pain in different parts of the body. For example, chronic back pain might be very different from chronic joint pain. Our current pain medications are not effective as treatments for many forms of chronic pain. The lack of good treatments has contributed to the increase in opioid prescriptions that led to opioid addiction crisis. Identifying more specific causes of chronic pain could give researchers ideas for better ways to treat it.
About the brief writer: Patti Murphy
Patti is a PhD Candidate in Michael Granato's lab. Patti is interested in understanding and developing therapeutics for functional nerve regeneration, particularly to restore voluntary motor control after spinal cord injury.