A dermatome is an area of the body supplied by a single spinal nerve ganglion. Physical sensations (and as such, autonomic/spinal reactions) are controlled by these nerves.
Technically "dermatome” only refers to the skin supplied by that nerve (derma - “skin”, -tome “single section”), but as the lower graphics show, we’ve also determined what nerves control the sensations of our muscles.
As you can see in the graphic of the trigeminal nerve innervation at the top, there’s a moderate amount of variation between individuals, but the basic layout is generally the same.
Because the basic layout of our nerves is known, when someone damages a nerve, which nerve has been damaged can sometimes be determined by what area of the skin has abnormal sensations. A few years ago, I damaged my elbow at work, and it was determined that my ulnar nerve had been affected, due to the lower third of my arm and hand being numb. Thankfully it’s since recovered, but in some situations, nerve damage can cause permanent altering of sensation in the parts of the body affected.
Atlas of Applied (Topographical) Human Anatomy for Students and Practitioners. J. Howell Evans, 1906.
(Image caption: Marked as concentrated yellow here, a unique population of astrocytes in the dorsal horn of the mouse spinal cord have been found to play a role in controlling pain)
New mechanism of pain control revealed
Researchers in Japan have revealed a previously unknown mechanism for pain control involving a newly identified group of cells in the spinal cord, offering a potential target for enhancing the therapeutic effect of drugs for chronic pain.
While neurons may be the most well-known cells of the central nervous system, an assortment of non-neuronal cells first discovered in the mid-nineteenth century also play a wide variety of important roles.
Originally named after the Greek word for “glue,” these glial cells are now known to be much more than glue and in fact are critical elements for regulating neuronal development and function in the central nervous system.
Among the different types of glial cells, astrocytes are the most abundant in the central nervous system, but, unlike neurons in different brain regions, researchers still have yet to develop a detailed understanding of groupings of astrocytes with distinct properties.
Now, researchers led by Makoto Tsuda, professor at Kyushu University’s Faculty of Pharmaceutical Sciences, have discovered a unique population of spinal cord astrocytes with a role in producing pain hypersensitivity.
Found in the outer two layers of gray matter near the back of the spinal cord—a location referred to as the superficial laminae of the spinal dorsal horn—the astrocytes are in a region known to carry general sensory information such as pressure, pain, and heat from around the body to the brain.
Using mice, the researchers showed that stimulating noradrenergic (NAergic) neurons—so called for their use of noradrenaline as a neurotransmitter—that carry signals from the locus coeruleus (LC) in the brain down to the spinal dorsal horn activates the astrocytes and that the astrocyte activation results in pain hypersensitivity.
(Image caption: Descending LC-NAergic neurons are well known to suppress pain transmission in the spinal dorsal horn. However, researchers uncovered a new role of descending LC-NAergic neurons in facilitating spinal pain transmission by identifying a new population of spinal cord astrocytes)
These observations overturn the prevailing view that descending LC-NAergic neurons suppress pain transmission in the spinal dorsal horn.
“The discovery of this new population of astrocytes reveals a new role of descending LC-NAergic neurons in facilitating spinal pain transmission,” explains Tsuda.
Considering these findings, suppressing signaling of these astrocytes by noradrenaline may enhance the effect of drugs for chronic pain.
To initially test this, the researchers genetically engineered mice in which response of astrocytes to noradrenaline was selectively inhibited and gave them duloxetine, an analgesic drug thought to increase levels of noradrenaline in the spinal cord by preventing uptake by descending LC-NAergic neurons.
Indeed, the modified mice exhibited an enhanced easing of chronic pain by duloxetine, further supporting the researchers’ proposed role of the astrocytes.
“Although we still need more studies with different drugs, this astrocyte population appears to be a very promising target for enhancing the therapeutic potential of drugs for chronic pain,” says Tsuda.
Researchers Discover New Path to Neuron Regeneration After Spinal Cord Injury
Dynamic networks that specialize in the transmission of information generally consist of multiple components, including not only primary processors, like computers, for example, but also numerous support applications and services. The human nervous system is fundamentally very similar—neurons, like computers, process and transmit information, sending molecular signals through axons to other neurons, all of which are supported by non-neuronal components, including an array of cells known as glia.
Glial cells carry out a variety of support and maintenance functions, and one type in particular – the astrocytic glial cell – has the unique ability to form scar tissue around damaged neurons. The presence of scar tissue is associated with inhibitory effects on the regrowth of mature neurons that are damaged by spinal cord injury. Recent evidence suggests, however, that these inhibitory effects are reversible, and in new work, scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) and the University of Pennsylvania show that astrocytic glial cells can in fact play a major role in facilitating neuron repair.
“We found that glia have a metabolic switch associated with glucose metabolism that when triggered reverses inhibitory effects on growth and promotes axon regeneration,” explained Shuxin Li, MD, PhD, Professor of Anatomy and Cell Biology at Shriners Hospital's Pediatric Research Center at LKSOM, and a senior investigator on the new study.
The research, published September 16 in the journal Cell Metabolism, is the first to establish a link between glucose metabolism in glial cells and functional regeneration of damaged neurons in the central nervous system.
In collaboration with senior investigator Yuanquan Song, PhD, Assistant Professor of Pathology and Laboratory Medicine at the University of Pennsylvania Perelman School of Medicine, Dr. Li and colleagues set out to investigate how scar tissue formation induced by glial cells impacts axon regeneration, using both fly and mouse models of axon injury. In initial experiments, they confirmed what previous studies had indicated, that the negative effects of glial cell activity on axon regeneration are indeed reversible. But the researchers also found that the switch between positive and negative effects on axon regrowth is directly related to the glial cells' metabolic status.
In follow-up experiments in flies, the researchers focused specifically on glycolysis – the metabolic pathway responsible for the breakdown of glucose – and discovered that upregulating this pathway alone in glial cells was sufficient to promote axon regeneration. This same result was observed in mice. Further investigation in fly and mouse models led to the identification of two glucose metabolites, lactate and hydroxyglutarate, that act as key mediators of the glial switch from an inhibitory reaction to a stimulatory response.
“In the fly model, we observed axon regeneration and dramatic improvements in functional recovery when we applied lactate to damaged neuronal tissue,” Dr. Li said. “We also found that in injured mice, treatment with lactate significantly improved locomotor ability, restoring some walking capability, relative to untreated animals.”
Dr. Li and colleagues examined the specific pathway by which lactate and hydroxyglutarate act to enhance axon regeneration. Experiments revealed that when glial cells are activated, they release glucose metabolites, which subsequently attach to molecules known as GABAB receptors on the neuron surface and thereby activate pathways in neurons that stimulate axon growth.
“Our findings indicate that GABAB receptor activation induced by lactate can have a critical role in neuronal recovery after spinal cord injury,” Dr. Li said. “Moreover, this process is driven by a metabolic switch to aerobic glycolysis, which leads specifically to the production of lactate and other glucose metabolites.”
The researchers plan next to test the regenerative abilities of lactate and related molecules in larger animals and to determine which molecules are most effective for promoting regeneration. “The next phases of our work could set the stage for future translational studies in human patients affected by spinal cord injury,” Dr. Li added.
(Image caption: The researchers studied the organization of interneurons in the spinal cord, like those shown here. Credit: Salk Institute)
When it comes to feeling pain, touch or an itch, location matters
When you touch a hot stove, your hand reflexively pulls away; if you miss a rung on a ladder, you instinctively catch yourself. Both motions take a fraction of a second and require no forethought. Now, researchers at the Salk Institute have mapped the physical organization of cells in the spinal cord that help mediate these and similar critical “sensorimotor reflexes.”
The new blueprint of this aspect of the sensorimotor system, described online in Neuron, could lead to a better understanding of how it develops and can go awry in conditions such as chronic itch or pain.
“There’s been a lot of research done at the periphery of this system, looking at how cells in the skin and muscles generate signals, but we didn’t know how that sensory information is trafficked and interpreted once it reaches the spinal cord,” says Martyn Goulding, a professor in Salk’s Molecular Neurobiology Laboratory and holder of the Frederick W. and Joanna J. Mitchell Chair. “This new work gives us a fundamental understanding of the architecture of our sensorimotor system.”
Reflexive behaviors—seen even in newborn babies—are considered some of the simplest building blocks for movement. But reflexes must quickly translate information from sensory neurons that detect touch, heat and painful stimuli to motor neurons, which cause the muscles to take action. For most reflexes, the connections between the sensory neurons and motor neurons are mediated by interneurons in the spinal cord, which serve as sort of “middlemen,” thereby saving time by bypassing the brain. How these middlemen are organized to encode reflexive actions is poorly understood.
Goulding and his colleagues turned to a set of molecular engineering tools they’ve developed over the past decade to examine the organization of these spinal reflexes in mice. First, they mapped which interneurons were active when mice responded reflexively to sensations, like itch, pain or touch. They then probed the function of interneurons by turning them on and off individually and observing how the resulting reflex behaviors were affected.
“What we found is that each sensorimotor reflex was defined by neurons in the same physical space,” says postdoctoral researcher Graziana Gatto, the first author of the new paper. “Different neurons in the same place, even if they had very different molecular signatures, had the same function, while more similar neurons located in different areas of the spinal cord were responsible for different reflexes.”
Interneurons in the outermost layer of the spinal cord were responsible for shuttling reflexive messages related to itch between sensory and motor cells. Deeper interneurons relayed messages of pain—causing a mouse to move a foot touched by a pin, for instance. And the deepest set of interneurons helped mice reflexively keep their balance, stabilizing their body to prevent falling. But within each spatial area, neurons had varying molecular properties and identities.
“These reflexive behaviors have to be very robust for survival,” says Goulding. “So, having different classes of interneurons in each area that contribute to a particular reflex builds redundancy into the system.”
By demonstrating that the location of each interneuron type within the spinal cord matters more than the cell’s developmental origin or genetic identity, the team tested and confirmed an existing theory about how these reflex systems are organized.
Now that they know the physical architecture of the interneuron circuits that make up these different reflex pathways, the researchers are planning future studies to reveal how messages are conveyed and how the neurons within each space interact with each other. This knowledge is now being used to probe how pathological changes in the somatosensory system result in chronic itch or pain. In an accompanying paper, Gatto and Goulding collaborated with Rebecca Seal of the University of Pittsburgh to map the organization of neurons that generate different forms of chronic pain.
When people suffer spinal cord injuries and lose mobility in their limbs, it's a neural signal processing problem. The brain can still send clear electrical impulses and the limbs can still receive them, but the signal gets lost in the damaged spinal cord.
The Center for Sensorimotor Neural Engineering (CSNE) -- a collaboration of San Diego State University with the University of Washington and the Massachusetts Institute of Technology -- is working on an implantable brain chip that can record neural electrical signals and transmit them to receivers in the limb, bypassing the damage and restoring movement. Recently, these researchers described in a study published in the journal Nature Scientific Reports a critical improvement to the technology that could make it more durable, last longer in the body and transmit clearer, stronger signals.
The technology, known as a brain-computer interface, records and transmits signals through electrodes, which are tiny pieces of material that read signals from brain chemicals known as neurotransmitters. By recording brain signals at the moment a person intends to make some movement, the interface learns the relevant electrical signal pattern and can transmit that pattern to the limb's nerves, or even to a prosthetic limb, restoring mobility and motor function.
The current state-of-the-art material for electrodes in these devices is thin-film platinum. The problem is that these electrodes can fracture and fall apart over time, said one of the study's lead investigators, Sam Kassegne, deputy director for the CSNE at SDSU and a professor in the mechanical engineering department.
Kassegne and colleagues developed electrodes made out of glassy carbon, a form of carbon. This material is about 10 times smoother than granular thin-film platinum, meaning it corrodes less easily under electrical stimulation and lasts much longer than platinum or other metal electrodes.
"Glassy carbon is much more promising for reading signals directly from neurotransmitters," Kassegne said. "You get about twice as much signal-to-noise. It's a much clearer signal and easier to interpret."
The glassy carbon electrodes are fabricated here on campus. The process involves patterning a liquid polymer into the correct shape, then heating it to 1000 degrees Celsius, causing it become glassy and electrically conductive. Once the electrodes are cooked and cooled, they are incorporated into chips that read and transmit signals from the brain and to the nerves.
Researchers in Kassegne's lab are using these new and improved brain-computer interfaces to record neural signals both along the brain's cortical surface and from inside the brain at the same time. "If you record from deeper in the brain, you can record from single neurons," explained Elisa Castagnola, one of the researchers. "On the surface, you can record from clusters. This combination gives you a better understanding of the complex nature of brain signaling."
A doctoral graduate student in Kassegne's lab, Mieko Hirabayashi, is exploring a slightly different application of this technology. She's working with rats to find out whether precisely calibrated electrical stimulation can cause new neural growth within the spinal cord. The hope is that this stimulation could encourage new neural cells to grow and replace damaged spinal cord tissue in humans. The new glassy carbon electrodes will allow her to stimulate, read the electrical signals of and detect the presence of neurotransmitters in the spinal cord better than ever before.
The SDSU-UW-MIT collaboration was initially funded in 2011 by an $18.5 million grant from the National Science Foundation. In 2015, this grant was renewed, providing an additional $15 million to $20 million to the researchers. Each of the universities in the collaboration focuses on particular areas of expertise, but they work closely on the shared goal of ultimately restoring motor function to people with nervous system injuries by furthering what's possible with brain-computer interfaces.