9.1 Somatosensory Receptors

Touch receptors

Merkel disk, Meissner’s corpuscle, Ruffini endings, and Pacinian corpuscle all serve to transduce features of touch sensation. These disks and corpuscles are specialized structures in the skin that are connected to axons that send touch information to the spinal cord. These terminal structures are the starting points of the somatosensory system, so they are also called "sensory receptors". Here the term "receptor" is different from the neurotransmitter receptor on the cell membrane (much smaller, one protein molecule). The sensory receptor is a much larger structure (composed of many proteins). Within these specialized endings sit mechanosensitive cation channels which activate in response to mechanical pull from sensations like touch, pressure, and vibration. These channels, also called piezo channels, are permeable to Na⁺, K⁺, Ca²⁺, and Mg²⁺, with a slight preference for Ca²⁺. Figure 9.3 shows the protein structure of two major piezo channels. They both are made of 3 proteins that come together to form a central pore, through which ions move, with blade-like structures surrounding the pore. The discovery of piezo channels led to a Nobel prize in 2021 for Dr. Ardem Patapoutian, the scientist who first described them (Coste et al., 2010) (Figure 9.3). Figure 9.4 shows how these channels open in response to mechanical force. The influx of ions through these channels leads to the generation of action potentials which propagate via highly myelinated Aβ fibers to the spinal cord.

Figure 9.3 Piezo channel structure Signals responsible for mechanosensation are transmitted by piezo channels. Piezo channels are composed of three proteins forming blades around a central pore.

Figure 9.4 PIEZO Channels: How Do They Allow Mechanosensation? PIEZO1 and PIEZO2 are both mechanically-activated cation channels. Based on protein structure, it was predicted that the 'blades' of the PIEZO channels undergo a lever-like flattening motion upon application of mechanical stress. This opens up their central pore, allowing an influx on positive charge. The exact mechanism by which mechanical force leads to the central pore opening is not fully understood.

The four major mechanoreceptors (Merkel disks, Meissner’s corpuscles, Ruffini endings, and Pacinian corpuscles) are each sensitive to different kinds of touch. The location and shape of each receptor structure supports these different sensitivities. Figure 9.5 summarizes these key features of the 4 receptor types. Next, we will review some key structural features of these receptors and how they support the receptor function.

Figure 9.5 Mechanorecpetor receptive fields and adaptations

First, their different locations in the skin help determine how large or small their receptive fields are, which for touch receptors means the area of the skin in which touch can activate them. Merkel disks and Meissner’s corpuscles are located more superficially around the epidermis and therefore have a smaller and clearly-defined receptive field. Ruffini endings and Pacinian corpuscles are located more in the deeper part of the skin (with a larger, blurry receptive field), near where hair follicles are located.

Second, the shape and composition of each touch receptor help determine how long they respond to stimuli, dividing them into rapid adapting versus slowly adapting receptors. The slowly adapting receptors include Merkel disk and Ruffini endings. When a force or stimulus is applied in their receptive field, those receptors will be constantly activated and generate electrical activities (e.g., pressure). On the other hand, the rapidly adapting receptors such as Meissner’s corpuscle and Pacinian corpuscle only respond or generate electrical activities when there is a dynamic change of forces or stimuli, such as vibration (Johansson and Vallbo, 1983; Koerber and Mendell, 1988). These adaptation properties combine with the receptive field to give the unique sensitivity of each of these 4 receptor types to specific touch modalities described in Table 9.1.

Nociceptors

The specific receptor for sensing a high-threshold stimulus that is damaging or threatens damage to normal tissues is called a nociceptor. Free nerve endings serve as nociceptors, or receptors that transmit pain signals related to mechanical, thermal, or chemical sources. Free nerve endings are different from the preceding four mechanoreceptors. The role of free nerve endings is related to sensing pain and temperature. Free nerve endings lack any specialized structures around their terminals and are connected to or in continuation with unmyelinated C-fibers and myelinated Aδ fibers. There are separate types of nociceptors responding to each modality (i.e., mechanical, thermal, and chemical), but also polymodal receptors that respond to all. Below we will discuss further how nociceptors sense tissue damage and temperature specifically.

Some free nerve endings transmit pain signals related to tissue damage (Figure 9.6). For example, if someone cut their finger, the direct and indirect damage of the nerve terminals (C- or Aδ fibers) at the primary injury site will excite and generate action potentials, which will not only propagate to the spinal cord (generating pain perception), but also propagate through the axonal branch points to spread to other axonal terminals that connect to the same main axon. The invasion of action potentials to the nearby uninjured axonal terminals will lead to the release of several key neural peptides, CGRP (calcitonin-gene related peptide) from Aδ fiber and SP (Substance P) from C-fiber, which cause vasodilatation (redness and temperature) and plasma extravasation (edema). This phenomenon is called axonal reflex, a mechanism contributing to neurogenic inflammation. The primary injury also breaks blood vessels, leading to the accumulation of white blood cells, especially the mast cell. Mast cells can also release these neuropeptides and stimulate the axonal terminals and capillaries, leading to redness (rubor), heat (color), swelling (tumor), pain ( dolor), and loss of function (functio laesa), cardinal signs of inflammation.

Figure 9.6 Local mechanisms of nociception

Other free nerve endings contain transient receptor potential (TRP) channels, which are temperature-sensitive mechanoreceptors. TRP channels open in response to temperature and come in a variety of types, each one sensitive to a different temperature. Figure 9.7 reviews the temperature sensitivities of several kinds of TRPs. Dr. David Julius, also pictured in Figure 9.7, shared the 2021 Nobel Prize in Physiology or Medicine for his description of these channels. Figure 9.8 shows an example of how heat causes a warm-sensing TRP channel to open, allowing in positive ions that activate the free nerve ending, which then relays signals to the brain via the spinal cord.

Figure 9.7 The TRP ion Channels Signals responsible for temperature and pain sensation are transmitted by transient receptor potential (TRP) channels that activate across different temperature ranges.

Figure 9.8 TRP channels transduce temperature information

One notable example of a TRP channel is the capsaicin receptor. Capsaicin is the key chemical ingredient in hot chili peppers. When it binds to the capsaicin receptors, it activates a TRP channel (Samanta et al., 2018) that allows calcium ions to flow into the cell, leading to depolarization (Caterina et al., 1997; Julius, 2013). This is the same channel activated by hot temperatures, which is why a spicy pepper feels hot . A similar, but separate TRP channel activates in response to cold temperatures, as well as chemicals in foods that feel cold, like mint. Activation of TRP channels, therefore, transmit information about temperature, and also are part of our experience of temperature sensations associated with a number of chemicals (see Chapter 8 The Chemical Senses).

Hair follicle mechanosensation

Throughout our body, the skin can be divided into hairy and glabrous skin (mainly on the palms and soles). In the hairy skin, an axonal terminal wraps around the bottom of the hair, the hair follicle, in the dermis. The reason why we can feel a breeze blowing across our faces is that all those tiny hairs (vellus hair, or peach fuzz) are bent by the airflow. The force is transduced to the hair follicles in the skin, causing the slightest displacement (in terms of nanometers). The follicle displacement causes a stretch of the axonal membrane wrapped around the follicle. There are many mechanosensitive Na⁺ channels in this wrapping axon, which open in response to this stretch. That is how we can feel the movement of hair. If the hair is pulled too hard, it can generate pain.