December 17, 2019
Written by: Nitsan Goldstein
Try touching the nail of your pointer finger to your thumb and slowly increasing the pressure. At first, you feel the presence of the nail on your skin. As you push into the skin you feel the increase in pressure as well as a sharp sensation. If you push hard enough, you will start to feel pain. Aside from pressure and pain we can also feel heat, cold, and movement on our skin. How does the brain distinguish between all this sensory information? Here we will discuss the neural basis of touch at three points in the pathway of information: the skin, the spinal cord, and the brain.
Step 1: Sensory Neurons in the Skin
The neurons that first transmit information about touch, temperature, and pain are called sensory neurons. The cell bodies of these neurons are in a structure called the dorsal root ganglion, found outside the spine. From here, they send one projection to the periphery (often the skin), and one to the spinal cord (Figure 1).
There are many types of sensory neurons that are defined by several characteristics. For example, the size of the neuron and the degree to which their projections are myelinated varies. Myelin wraps around neurons and insulates them, greatly increasing the speed at which action potentials travel down a neuron. One class of sensory neurons, called C-fibers, are small and unmyelinated, meaning information travels relatively slowly from the periphery to the brain. Aβ neurons, on the other hand, are large and heavily myelinated while Aδ neurons fall in between the two. In general, C- and Aδ-fibers carry information about pain and temperature, while Aβ-fibers transmit touch information, though there is significant overlap within these classifications1. Both types of neurons are involved in the pain you feel when you stub your toe, namely the sharp, fast pain followed by a longer lasting, duller pain. The sharp pain is due to the high speed at which action potentials reach the spinal cord via the myelinated Aδ fibers. The information from C-fibers takes much longer to reach the central nervous system, resulting in the slower, duller pain that follows.
At the skin, the neurons contain receptors that respond to different kinds of touch sensations using proteins called mechanoreceptors. The mechanoreceptors open in response to physical displacement, causing the neuron to send a signal. Some neurons contain low-threshold mechanoreceptors (LTMRs), while others contain high-threshold mechanoreceptors (HTMRs). The LTMRs need only a slight stretch to open and activate the neuron, while the HTMRs need a much greater degree of stretch. The kind of receptors present in the neuron will also determine whether they respond to heat, cold, sharp or dull touch, and motion.
The combination of these and other characteristics allow these neurons to respond to very specific stimuli. When you gently touched your nail to your finger, you only activated the LTMRs, for example. But when you increased the pressure, the increased stretch to the skin also activated the HTMRs. The electrical signals these sensory neurons send to the spinal cord, however, are very similar. How do we get from activation of these neurons to the complex sensations of touch and pain?
Step 2: The Spinal Cord
The key to properly interpreting generic electrical signals from these different kinds of sensory neurons is keeping their pathways segregated until they reach the brain (see Figure 1). If the brain knows which kind of sensory neuron the signal originated from, it can figure out what kind of stimuli generated that electrical signal and interpret the information. Sensory neurons send messages to a region in the spinal cord called the dorsal horn. Neurons carrying different types of sensory information enter the spinal cord through different layers of the dorsal horn (Figure 1- dotted black lines in the dorsal horn) and take different pathways up to the brain. The less myelinated neurons (C- and Aδ-fibers) stop in the outer layers of the dorsal horn and in turn activate other neurons here. These neurons cross to the other side of the spinal cord and then travel up all the way to the brain.
In contrast, neurons transmitting touch information (mainly via Aβ-fibers) travel to the deeper layers of the dorsal horn. Unlike the neurons carrying pain information that terminate in the dorsal horn, most of the Aβ neurons project all the way up to the base of the brain, where they terminate in a hindbrain region called the medulla (see Figure 1). There, they form connections with other neurons that transmit the information to the brain. This brings us to our final stop in touch and pain sensation: the brain.
Step 3: The Brain
Neurons transmitting any kind of touch sensation end in the thalamus, a region of the brain that is a critical first stop for sensory information. The thalamus also receives auditory and visual information, and is responsible for relaying all of these different types of information to the proper regions of the cortex—the outer part of the brain—to be processed.
Touch information is transmitted to the somatosensory cortex. It is here where the conscious sensation of touch arises. Remember that information traveled along segregated pathways, with organization based on which kind of sensory neuron was first activated and where in the body it was active. This is critical because now, the brain can interpret the signal it receives based on which pathway it came from and from where it came within that pathway.
Other areas of the brain are also involved in sensing touch, especially when the stimuli are strong and painful. Neurons originating in the spinal cord and hindbrain project to several other areas like the amygdala. Activation of these pathways produces fear and the other unpleasant feelings associated with sensations of high heat, extreme cold, or strong mechanical force. It is this elaborate organization that allows us to perceive an extremely wide range of stimuli and respond appropriately. What happens, though, when some of this organization breaks down, and information is interpreted incorrectly?
When Wires Get Crossed
The fact that information is transmitted in organized routes based on which sensory neuron it came from is what allows simple electrical signals to be interpreted as complex sensations like a poke, stroke, and cool breeze. It also means that at any point along the route, information can get crisscrossed, resulting in an incorrect interpretation of sensory stimuli. One example is a condition called allodynia, a condition that often follows a nerve injury. When someone suffers from allodynia, a light touch that would normally not be painful becomes very painful.
While the exact cause of allodynia is not fully understood, several theories have been proposed that could explain how a normally innocuous (non-painful) touch stimulus would be painful2. One possibility is that, following injury, low-threshold mechanoreceptor (LTMR) neurons that sense gentle touch re-grow incorrectly into the outer layer of the dorsal horn, where pain information is normally sent. The brain, receiving signals from the outer layer, interprets them as painful3. Other theories include changes in the sensitivity of the receptors themselves in pain-sensing neurons. These changes cause them to respond to innocuous touch, which would also be interpreted by the brain as painful2.
It is conditions like allodynia that show us just how complex touch sensation is. Each type of neuron responds to a unique set of stimuli, and the dozens of different types of neurons together allow us to sense and distinguish between all kinds of surfaces, temperatures, and pressures. This ability is not only critical for manipulating objects and responding to pain, but plays a pivotal role in our social interactions as well. Touch is important in mother-infant bonding, and gentle stroking of hairy skin reduces stress and anxiety in animals and humans4. Understanding how this intricate system works will continue to be a major research focus for years to come.
- Abraira, V. E. & Ginty, D.D. The Sensory Neurons of Touch. Neuron 79, 618-639 (2013).
- Colloca, L., et al. Neuropathic Pain. Rev. Dis. Primers 3, 17002 (2017).
- Woolf, C.J., Shortland, P., & Coggeshall, R.E. Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 355, 75-78 (1992).
- Cascio, C.J., Moore, D., & McGlone, F. Social touch and human development. Cog. Neuro. 35, 5-11 (2019).
Cover Photo from Pexels https://www.pexels.com/photo/baby-child-father-fingers-451853/
Figure 1 created using BioRender