Learning Objectives
By the end of this section, you should be able to
- 9.2.1 Describe the anatomy of the spinal cord, thalamus, and somatosensory cortices.
- 9.2.2 Define the ascending and descending pathways that are involved in transmitting somatosensory information.
- 9.2.3 Explain the Gate Control theory.
- 9.2.4 Describe how information flow to the limbic system contributes to the emotional response to pain.
From the cutaneous sensory receptors, action potentials travel through the dorsal horn to reach the lowest part of the central nervous system, the spinal cord. Axons with various levels of myelination and diameter synapse on the spinal cord dorsal horn or dorsal medulla neurons, then ascend to other levels in the brain, including the major relay station in the thalamus, and finally reach the primary somatosensory cortex where sensory perception happens. In this section, we will explain how sensory information is organized and processed from the dorsal horn of the spinal cord up to the brain, where we consciously perceive it.
Spinal Cord
The spinal cord is the lowest component of the central nervous system. It facilitates the transmission of body sensory information to the brain, as well as transmission of motor commands and autonomic nervous system modulation of internal organs from the brain to the body.
Anatomy of the spinal cord and dermatomes
The spinal cord has 31 segments, divided along the rostral-caudal axis into cervical (8), thoracic (12), lumbar (5), sacral (5), and coccygeal (1) segments. The spinal cord can also be divided into the dorsal versus ventral parts. While the ventral part is mainly involved in the processing of the motor system, the dorsal part is mainly sensory input. As covered in Chapter 1 Structure and Function of the Nervous System: Cells and Anatomy and reviewed in Figure 9.11, in the spinal cord, the central part (shaped like a butterfly) is composed of neuronal cell bodies and dendrites (gray matter), which are surrounded by axons (white matter). Each segment of the spinal cord has two pairs of nerve bundles, the dorsal roots for sensory input and the ventral roots for motor output, as well as for sympathetic output. Because of this unique organization, the body surface is represented by different segments of the spinal cord, each of which is called a dermatome (Figure 9.11) (Joseph and Loukas, 2015). In the spinal cord, the primary afferent axons synapse on the spinal cord neurons, or head straight up to the brain. The dorsal horn neurons can be subdivided into several laminae (or layers), each of which relays specific aspects of touch (laminae III-V) or pain (laminae I&II).
Neurotransmitters and receptors in the spinal cord
A variety of neurotransmitters serve somatosensation in the spinal cord. Though we often represent touch information as traveling directly from the receptors on through to the brain, in reality, multiple types of neurons are involved in a complex communication within the spinal cord, helping to determine what sensory information is conveyed to higher centers in the brain or to local reflex circuits. The participating neurons include the primary afferent terminals we already discussed, along with descending fibers coming from the supraspinal origin, and intrinsic neurons inside the spinal cord. Neurotransmitters from each of these classes of neurons work in combinations to maintain the excitability of the spinal sensory neurons. In general, all primary afferent fibers use glutamate as the major excitatory neurotransmitter; Aδ fiber and C fibers also contain CGRP and SP, respectively. CGRP and SP can also be released in peripheral tissue by primary afferents, which we discussed earlier when we learned about their role in axonal reflex and neurogenic inflammation (Figure 9.6). Descending fibers and spinal interneurons can release a variety of neurotransmitters, many of which will sound familiar from other chapters, such as glutamate, GABA, neurokinins, nerve growth factor, ATP, neuropeptides (e.g., substance P), CGRP, bradykinin, cannabinoids, endorphins, cytokines, nitric oxide, ATP. These neurotransmitters interact with a variety of different types of receptors resulting in excitation, inhibition, or neuromodulation. The end result is a complex network of regulation within the spinal cord to determine what sensory signals pass to the brain and what signals do not.
Gate control theory
Gate control theory provides an example of the kind of communication that can occur within the spinal cord to determine what information is passed on to the brain. This theory was proposed by Ronald Melzack and Patrick D. Wall in 1965 (Melzack and Wall, 1965). It indicates that somehow in the spinal cord there is a gate that only allows so much information to flow forward to the brain at any given point in time. In this theory, a gate for pain information is controlled by two different types of inputs, neurons carrying primary sensory information (touch or pain), and an inhibitory interneuron, both of which combine to influence whether a projection neuron sends pain information towards the brain.
Figure 9.12 diagrams this theory. In this model, activity of a pain projection neuron is controlled by a nociceptive C fiber, as well as a non-nociceptive A-fiber and an inhibitory interneuron. In response to a painful stimulus, the unmyelinated C-fiber that is responsible for pain activates the projection neuron and inhibits the inhibitory interneuron in the spinal cord. Both of these activities open the gate to increase pain (Figure 9.12). The gate can be closed by the large myelinated A-fiber. The A-fiber, which transmits touch and vibration sensation, has 2 connections in this circuit: it excites the projection neuron weakly and it excites the inhibitory interneuron strongly. Strong A-fiber activation net inhibits the pain projection neuron through activation of more inhibitory interneuron activity in the spinal cord. This inhibition shuts down the gate, relieving the pain.
If you happen to hammer your finger, almost immediately you will shake your hand or rub or blow air to your injured finger to reduce pain. When you do this, you are using the “Gate Control Theory”. While shaking or rubbing, Aα/Aβ fibers are activated. Although there is an increased input from C-fibers as the result of injury for increased pain, activation of Aα/Aβ fibers will excite more inhibitory interneurons that will release GABA to the projection neurons to counteract or inhibit the injury-elicited pain. Though there are some aspects of pain sensation that have been found to contradict the Gate Control theory since its proposal in 1965, it remains the single most critical model of pain sensation processes.
Ascending pathways and their roles: from the spinal cord to the thalamus
As the sensory information comes to the spinal cord from the periphery, it will be processed inside the spinal cord first, then it will take two major systems to reach the brain. The first one is the dorsal column-medial lemniscal pathway for touch and pressure sensation and proprioception as shown in Figure 9.14. In this pathway, the primary afferent fibers ascend in the dorsal column ipsilaterally all the way to the medulla. They then synapse on the dorsal column nuclei in the medulla (i.e., nucleus gracilis and nucleus cuneatus). The axons from these dorsal column neurons in the medulla (2nd order neurons) project to the contralateral side to form a bundle, the medial lemniscus, which synapse on third-order neurons in the thalamus. From there, the thalamocortical projections from these thalamic neurons go to the primary somatosensory cortex (S1).
The second major pathway for somatosensation to the brain is the anterolateral system (i.e., located at the anterior and lateral part of the spinal cord), which originates in the spinal cord cells receiving pain and temperature input. The anterolateral system projects to the supraspinal areas through five main pathways (Willis, 1985; Willis and Westlund, 1997). The spinothalamic tract (STT) is the most prominent pain and temperature pathway (Figure 9.15). It originates from nociceptive-specific and wide dynamic range neurons in the dorsal horn of the spinal cord, and ends at the contralateral ventral posterolateral nucleus of the thalamus. Unlike the touch pathway, the STT crosses the midline in the spinal cord, at the same spinal level where primary afferents entered through the dorsal horn. In the STT, the projections from the spinal neurons proceed up the contralateral spinal column, to the thalamus.
Figure 9.13 provides a side-by-side comparison of this major difference in where each of these major pathways crosses the midline. Note how ascending touch information is in the ipsilateral spinal cord, while pain and temperature information is in the contralateral spinal cord to where the sensory information originated. For an interesting clinical implication of this difference between pain and touch pathways, try to do internet research on Brown-Sequard Syndrome and see if you can explain the clinical symptoms and signs.
The remaining four pathways of the anterolateral system deal mostly with emotional and autonomic aspects of pain, and frequently project bilaterally in the brain. They are the spinoreticular tract (arousal), the spinomesencephalic tract (affective components of pain), the spinohypothalamic tract (to the autonomic control centers for fight or flight), and the cervicothalamic tract (playing a minor role).
Because of these different tracts that contribute to the sensory information propagation from the periphery to the brain, we will be able to not only sense the location and the intensity of somatosensory input but also generate emotional responses. Imagine that you are hiking in the late afternoon. It is getting dark, and you are tired. Every step you have is almost automatic. Then you step into a pothole, and sprain your ankle… The C-fiber or Aδ-fibers around your ankle constantly send action potentials to your spinal cord, activating the dorsal horn neurons. Through STT system, your brain knows where the pain is coming from and how strong it is. Activation of the spinoreticular system will boost your arousal level (see Chapter 15 Biological Rhythms and Sleep), whereas activation of the spinohypothalamic system will raise your sympathetic activity to increase your heart rate and blood pressure. Finally, if you are lucky and have a strong network of descending inhibitory systems (see below), through the spinomesencephalic tract, brainstem structures will be activated and send inhibitory signals to the lumbar spinal cord to reduce the spinal cord dorsal horn neuron activity, a self-built “closed-loop feedback” system that helps the individual to cope with pain.
Descending inhibitory pathways
As we mentioned in our earlier discussion of the neurons that control spinal-level transmission of sensory information, our brain is organized in a way to not only receive ascending input from the periphery, but also to manage inputs through a descending system sending projections downward at different levels (Sandkuhler et al., 1987; Jones and Gebhart, 1988; Millan, 2002). This protective measure enables the individual’s ongoing performance without being distracted by pain. For example, when injuries happen to soldiers on the battlefield or athletes in sports competitions, they do not feel that much pain due to the strong activation of the descending inhibition. It is believed that the center controlling the descending inhibition is located in the periaqueductal gray (PAG) in the midbrain (Figure 9.16).
Three major inhibitory systems contribute to the descending inhibitory system that originates in the PAG. The first one is the endogenous opioid system that releases endorphins, which can inhibit the activities of the spinal cord dorsal horn pain projection neurons to reduce or block signals to the brain. The second one is the serotonergic system, with the cell bodies located in the nucleus raphe magnus (NRM) in the brainstem, which projects their axons to the spinal cord at different levels to release serotonin. When serotonin binds to their receptors in the spinal cord projection neurons, it suppresses their activity. The third system is the noradrenergic system. The cell bodies are located in the locus coeruleus (LC), or 'blue spot', a structure in the brainstem. The axons of the LC project down to the spinal cord and release neurotransmitter, norepinephrine/noradrenaline, which suppresses the activity of the spinal projection neurons. With the contribution of these three major descending inhibitory systems, a closed-loop of pain coping mechanism is established. However, it may vary from person to person. See more in emotional components of pain in the next main section.
Thalamus and other projections
The thalamus is the major gateway in our brain that processes not only somatosensory information but also auditory, visual, as well as gustatory information. There are several major subdivisions of the thalamus. It also contributes to modulating motor activities by communicating with the basal ganglion and the cerebellum. The major subgroup that relays the somatosensory information is the ventral posterior lateral (VPL) and ventral posterior medial (VPM) nuclei. The VPL is responsible for relaying signals coming from the trunk and extremities and is shown as the major relay in Figure 9.15. The VPM is just medial to the VPL and receives information from the head area. Neurons in either VPL or VPM are the third-order neurons that project to the primary somatosensory cortex (S1) for the perception of the sensory information in the body.
Cortical process of touch and pain
Somatosensory information first reaches the cortex in the primary somatosensory cortex (S1), in the postcentral gyrus in the anterior part of the parietal lobe. The sensory receptive areas of the body are represented on S1 as an inverted little person lying along the sulci and gyri of the cortical surface, shown in Figure 9.17. This person, known as a homunculus, is a distorted representation of a human body with the size of each body part proportionate to that area’s amount of sensory innervation. For example, the hand requires more cortical resources, and it, therefore, gets more surface area (and more neurons) dedicated to its representation. S1 sends most of its projections to the secondary somatosensory cortex (S2) for further sensory processing, though there is also a communication between S1 and the motor cortices in the frontal lobe for sensory-guided motor function.
The mainstream of information after S1 and S2 flows posteriorly to reach the posterior parietal cortex, then to the temporal association cortex, parahippocampal cortex, and the cingulate cortex. The posterior parietal area receives information not only from the somatosensory cortex but also from auditory, and visual cortices. Information can therefore be integrated here from multiple modalities and then project to the prefrontal area where the integrated information can be analyzed, a decision can be made, and the motor response can be planned. Projections to the limbic system also play a critical role in processing our emotional response to somatosensory information, particularly pain or itch (Bushnell et al., 2013). The contribution of the combination of limbic system activities enables the individual to experience and integrate their emotion (e.g., anger, fear, anxiety, depression) in response to peripheral input (e.g., visual, sound, pain) or retrieval from the past experience (memory), to generate physiological responses (heart rate and blood pressure) or psychological experiences (Gilam et al., 2020). We will discuss this limbic component of pain more in the next section.