Somatic sensation is the most widespread and diverse of the body's sensory systems (soma means “body” in Greek). Its receptors are distributed throughout the body instead of being condensed into small and specialized sensory surfaces, as most other sensory systems are arranged. Somatosensory receptors cover the skin, subcutaneous tissue, skeletal muscles, bones and joints, major internal organs, epithelia, and cardiovascular system. These receptors also vary widely in their specificity. The body has mechanoreceptors to transduce pressure, stretch, vibration, and tissue damage; thermoreceptors to gauge temperature; and chemoreceptors to sense a variety of substances. Somatic sensation (or somesthesia) is usually considered to be a combination of at least four sensory modalities: the senses of touch, temperature, body position (proprioception), and pain (nociception).
A variety of sensory endings in the skin transduce mechanical, thermal, and chemical stimuli
To meet a wide array of sensory demands, many kinds of specialized receptors are required. Somatic sensory receptors range from simple bare nerve endings to complex combinations of nerve, muscle, connective tissue, and supporting cells. As we have seen, the other major sensory systems have only one type of sensory receptor or a set of very similar subtypes.
Mechanoreceptors, which are sensitive to physical distortion such as bending or stretching, account for many of the somatic sensory receptors. They exist throughout our bodies and monitor the following: physical contact with the skin, blood pressure in the heart and vessels, stretching of the gut and bladder, and pressure on the teeth. The transduction site of these mechanoreceptors is one or more unmyelinated axon branches. Our progress in understanding the molecular nature of mechanosensory transduction has been relatively slow. Similar to the transduction process in hair cells, that in cutaneous mechanoreceptive nerve endings probably involves the gating of ion channels. Some of these channels belong to the TRP superfamily (see Table 6-2, family No. 5).
Thermoreceptors respond best to changes in temperature, whereas chemoreceptors are sensitive to various kinds of chemical alterations. In the next three sections, we discuss mechanoreceptors, thermoreceptors, and chemoreceptors that are located in the skin.
Mechanoreceptors in the skin provide sensitivity to specific stimuli such as vibration and steady pressure
Skin protects us from our environment by preventing evaporation of body fluids, invasion by microbes, abrasion, and damage from sunlight. However, skin also provides our most direct contact with the world. The two major types of mammalian skin are hairy and glabrous. Glabrous skin (or hairless skin) is found on the palms of our hands and fingertips and on the soles of our feet and pads of our toes (Fig. 15-26A). Hairy skin makes up most of the rest and differs widely in its hairiness. Both types of skin have an outer layer, the epidermis, and an inner layer, the dermis, and sensory receptors innervate both. The receptors in the skin are sensitive to many types of stimuli and respond when the skin is vibrated, pressed, pricked, or stroked, or when its hairs are bent or pulled. These are quite different kinds of mechanical energy, yet we can feel them all and easily tell them apart. Skin also has exquisite sensitivity; for example, we can reliably feel a dot only 0.006 mm high and 0.04 mm across when it is stroked across a fingertip. The standard Braille dot is 167 times higher!
FIGURE 15-26 Sensors in the skin. (Data from Mendelson M, Loewenstein WR: Mechanisms of receptor adaptation. Science 144:554–555, 1964.)
The sensory endings in the skin take many shapes, and most of them are named after the 19th-century European histologists who observed them and made them popular. The largest and best-studied mechanoreceptor is Pacini's corpuscle, which is up to 2 mm long and almost 1 mm in diameter (see Fig. 15-26B). Pacini's corpuscle is located in the subcutaneous tissue of both glabrous and hairy skin. It has an ovoid capsule with 20 to 70 onion-like, concentric layers of connective tissue and a nerve terminal in the middle. The capsule is responsible for the rapidly adapting response of the Pacini's corpuscle. When the capsule is compressed, energy is transferred to the nerve terminal, its membrane is deformed, and mechanosensitive channels open. Current flowing through the channels generates a depolarizing receptor potential that, if large enough, causes the axon to fire an action potential (see Fig. 15-26B, left panel). However, the capsule layers are slick, with viscous fluid between them. If the stimulus pressure is maintained, the layers slip past one another and transfer the stimulus energy away so that the underlying axon terminal is no longer deformed and the receptor potential dissipates (see Fig. 15-26B, right panel). When pressure is released, the events reverse themselves and the terminal is depolarized again. In this way, the non-neural covering of Pacini's corpuscle specializes the corpuscle for sensing of vibrations and makes it almost unresponsive to steady pressure. Pacini's corpuscle is most sensitive to vibrations of 200 to 300 Hz, and its threshold increases dramatically below 50 Hz and above ~500 Hz. The sensation evoked by stimulation of Pacini's corpuscle is a poorly localized humming feeling.
Werner Loewenstein and colleagues in the 1960s showed the importance of the Pacini corpuscle's capsule to its frequency sensitivity. With fine microdissection, they were able to strip away the capsule from single corpuscles. They found that the resultant naked nerve terminal is much less sensitive to vibrating stimuli and much more sensitive to steady pressure. Clearly, the capsule modifies the sensitivity of the bare mechanoreceptive axon. The encapsulated Pacini corpuscle is an example of a rapidly adapting sensor, whereas the decapsulated nerve ending behaves like a slowly adapting sensor.
Several other types of encapsulated mechanoreceptors are located in the dermis, but none has been studied as well as Pacini's corpuscle. Meissner's corpuscles (see Fig. 15-26A) are located in the ridges of glabrous skin and are about one tenth the size of Pacini's corpuscles. They are rapidly adapting, although less so than Pacini's corpuscles. Ruffini's corpuscles resemble diminutive Pacini's corpuscles and, like Pacini's corpuscles, occur in the subcutaneous tissue of both hairy and glabrous skin. Their preferred stimuli might be called “fluttering” vibrations. As relatively slowly adapting receptors, they respond best to low frequencies. Merkel's disks are also slowly adapting receptors made from a flattened, non-neural epithelial cell that synapses on a nerve terminal. They lie at the border of the dermis and epidermis of glabrous skin. It is not clear whether it is the nerve terminal or epithelial cell that is mechanosensitive. The nerve terminals of Krause's end bulbs appear knotted. They innervate the border areas of dry skin and mucous membranes (e.g., around the lips and external genitalia) and are probably rapidly adapting mechanoreceptors.
The receptive fields of different types of skin receptors vary greatly in size. Pacini's corpuscles have extremely broad receptive fields (Fig. 15-27A), whereas those of Meissner's corpuscles (see Fig. 15-27B) and Merkel's disks are very small. The last two seem to be responsible for the ability of the fingertips to make very fine tactile discriminations. Small receptive fields are an important factor in achieving high spatial resolution. Resolution varies widely, a fact easily demonstrated by measuring the skin's two-point discrimination. Bend a paper clip into a U shape. Vary the distance between the tips and test how easily you can distinguish the touch of one tip versus two on your palm, your fingertips, your lips, your back, and your foot. To avoid bias, a colleague—rather than you—should apply the stimulus. Compare the results with standardized data (see Fig. 15-27C).
FIGURE 15-27 Receptive fields and spatial discrimination of skin mechanoreceptors. A, Each of the two black dots indicates an area of maximal sensitivity of a single Pacini corpuscle. Each blue-green area is the receptive field of a corpuscle (i.e., the corpuscle responds when stimulus strength increases sufficiently anywhere within the area). B, Each dot represents the entire receptive field of a single Meissner corpuscle. Note that the fields are much smaller than in A. C, The horizontal bars represent the minimum distance at which two points can be perceived as distinct at various locations over the body. Spatial discrimination depends on both receptor density and receptive-field size. (A and B, Data from Vallbo AB, Johansson RS: Properties of cutaneous mechanoreceptors in the human hand related to touch sensation. Hum Neurobiol 3:3–14, 1984; C, data from Weinstein S: Intensive and extensive aspects of tactile sensitivity as a function of body part, sex and laterality. In Kenshalo DR [ed]: The Skin Senses. Springfield, IL, Charles C Thomas, 1968.)
The identities of somatosensory transduction molecules remain elusive. A variety of TRP channel subtypes transduce mechanical stimuli in invertebrate species (e.g., Drosophila, Caenorhabditis elegans). In mammals, rapidly adapting ion channels are associated with receptors for light touch, and several of the TRPC channels appear to be involved in sensitivity to light touch in mice. A non-TRP protein named Piezo2 is associated with rapidly adapting mechanosensory currents in mouse sensory neurons, and knocking down the expression of Piezo2 expression causes deficits in touch. Other mechanosensory channels are expressed in some sensory neurons, including TRPA1 and TRPV4, two-pore potassium channels (KCNKs), and degenerin/epithelial sodium channels (especially ASIC1 to ASIC3 and their accessory proteins), but their roles in mammalian mechanosensation are still controversial.
One reason it is difficult to identify mechanosensory channels is that they often need to be associated with other cellular components in order to be sensitive to mechanical stimuli. The mechanisms by which mechanical force is transferred from cells and their membranes to mechanosensitive channels are unclear. Ion channels may be physically coupled to either extracellular structures (e.g., collagen fibers) or cytoskeletal components (e.g., actin, microtubules) that transfer energy from deformation of the cell to the gating mechanism of the channel. Mechanically gated ion channels of sensory neurons, including those requiring Piezo2, depend on the actin cytoskeleton. Some channels may be sensitive to stress, sheer, or curvature of the lipid bilayer itself and require no other types of anchoring proteins. Other channels may respond to mechanically triggered second messengers such as DAG (acting directly on the channel) or IP3 (acting indirectly via an IP3 receptor).
Two things determine the sensitivity of spatial discrimination in an area of skin. The first is the size of the receptors' receptive fields—if they are small, the two tips of your paper clip are more likely to stimulate different sets of receptors. The second parameter that determines spatial discrimination is the density of the receptors in the skin. Indeed, two-point discrimination of the fingertips is better than that of the palm, even though their receptive fields are the same size. The key to finer discrimination in the fingertips is their higher density of receptors. Crowding more receptors into each square millimeter of fingertip has a second advantage: because the CNS receives more information per stimulus, it has a better chance of detecting very small stimuli.
Although we rarely think about it, hair is a sensitive part of our somatic sensory system. For some animals, hairs are a major sensory system. Rodents whisk long facial vibrissae (hairs) and feel the texture, distance, and shape of their local environment. Hairs grow from follicles embedded in the skin, and each follicle is richly innervated by free mechanoreceptive nerve endings that either wrap around it or run parallel to it. Bending of the hair causes deformation of the follicle and surrounding tissue, which stretches, bends, or flattens the nerve endings and increases or decreases their firing frequency. Various mechanoreceptors innervate hair follicles, and they may be either slowly or rapidly adapting.
Separate thermoreceptors detect warmth and cold
Neurons are sensitive to changes in temperature, as are all of life's chemical reactions. Neuronal temperature sensitivity has two consequences: first, neurons can measure temperature; but second, to work properly, most neural circuits need to be kept at a relatively stable temperature. Neurons of the mammalian CNS are especially vulnerable to temperature changes. Whereas skin tissue temperatures can range from 20°C to 40°C without harm or discomfort, brain temperature must be near 37°C to avoid serious dysfunction. The body has complex systems to control brain (i.e., body core) temperature tightly (see pp. 1198–1201). Even though all neurons are sensitive to temperature, not all neurons are thermoreceptors. Because of specific membrane mechanisms, some neurons are extremely sensitive to temperature and seem to be adapted to the job of sensing it. Although many temperature-sensitive neurons are present in the skin, they are also clustered in the hypothalamus and the spinal cord (see pp. 1198–1199). The hypothalamic temperature sensors, like their cutaneous counterparts, are important for regulation of the physiological responses that maintain stable body temperature.
Perceptions of temperature apparently reflect warmth and cold receptors located in the skin. Thermoreceptors, like mechanoreceptors, are not spread uniformly across the skin. When you map the skin's sensitivity to temperature with a small cold or warm probe, you find spots ~1 mm across that are especially sensitive to either warmth or cold, but not to both. In addition, some areas of skin in between are relatively insensitive. The spatial dissociation of the hot and cold maps shows that they are separate submodalities, with separate receptors to encode each. Recordings from single sensory fibers have confirmed this conclusion. The responses of both warmth and cold thermoreceptors adapt during long stimuli, as many sensory receptors commonly do. Most cutaneous thermoreceptors are probably free nerve endings, without obvious specialization. Their axons are small, either unmyelinated C fibers or the smallest-diameter myelinated Aδ fibers (see Table 12-1).
We can perceive changes in our average skin temperature of as little as 0.01°C. Within the skin are separate types of thermoreceptors that are sensitive to a range of relatively hot or cold temperatures. Figure 15-28A shows how the steady discharge rate of both types of receptors varies with temperature. Warmth receptors begin firing above ~30°C and increase their firing rate until 44°C to 46°C, beyond which the rate falls off steeply and a sensation of pain begins, presumably mediated by nociceptive endings (see the next section). Cold receptors have a much broader temperature response. They are relatively quiet at skin temperatures of ~40°C, but their steady discharge rate increases as the temperature falls to 24°C to 28°C. Further decreases in temperature cause the steady discharge rate of the cold receptors to decrease until the temperature falls to ~10°C. Below that temperature, firing ceases and cold becomes an effective local anesthetic.
FIGURE 15-28 Temperature sensitivity of cutaneous thermoreceptors. A, The curves represent the mean steady firing rates of neurons from warmth receptors and cold receptors. B, These data from two experiments on cold receptors show the effects of cooling steps of similar magnitude but starting from different temperatures (20.5°C and 35°C). In both instances, the transient (phasic) responses are the same: an increase in the firing rate. When the starting temperature is 20.5°C, the final firing rate is less than the initial one. However, when the initial temperature is 35°C, the final rate is greater than the initial one. (Data from Somjen GG: Sensory Coding in the Mammalian Nervous System. New York, Appleton-Century-Crofts, 1972.)
In addition to the tonic response just described (i.e., the steady discharge rate), cold receptors also have a phasic response that enables them to report changes in temperature. As shown in Figure 15-28B, when the temperature suddenly shifts from 20.5°C to 15.2°C (both points are to the left of the peak in Fig. 15-28A), the firing rate transiently increases (i.e., the phasic response). However, the new steady-state level is lower, as suggested by the left pair of points in Figure 15-28A. When the temperature suddenly shifts from 35°C to 31.5°C (both points are to the right of the peak in Fig. 15-28A), the firing rate transiently increases, and the new steady-state level is higher, as suggested by the right pair of points in Figure 15-28A.
The transduction of relatively warm temperatures is carried out by several types of TRPV channels (specifically TRPV1 to TRPV4—see Table 6-2, family No. 5) expressed in thermoreceptors. TRPV1 is a vanilloid receptor—it is activated by the vanilloid class of compounds that includes capsaicin, the pungent ingredient that gives spicy foods their burning quality. Aptly enough, chili peppers taste “hot” because they activate some of the same ion channels that heat itself activates! TRPV1 and TRPV2 channels have painfully high temperature thresholds (~43°C and ~50°C, respectively) and thus help mediate the noxious aspects of thermoreception (see p. 387). Other TRPV channels (TRPV3 and TRPV4) are activated at more moderate temperatures and presumably provide our sensations of warmth.
Yet another TRP channel, TRPM8, mediates sensations of moderate cold. TRPM8 channels begin to open at temperatures below ~27°C and are maximally activated at 8°C. In a remarkable analogy to the hot-sensitive TRPV1 channel (the capsaicin receptor), the cool-sensitive TRPM8 channel is a menthol receptor. Menthol evokes sensations of cold because it activates the same ion channel that is opened by cold temperatures.
Nociceptors are specialized sensory endings that transduce painful stimuli
Physical energy that is informative at low and moderate levels can be destructive at higher intensity. Sensations of pain motivate us to avoid such situations. Nociceptors are the receptors mediating acutely painful feelings to warn us that body tissue is being damaged or is at risk of being damaged (as the Latin roots imply: nocere [to hurt] + recipere [to receive]). The pain-sensing system is entirely separate from the other modalities we have discussed; it has its own peripheral receptors and a complex, dispersed, chemically unique set of central circuits. Nociceptors are free nerve endings, widely distributed throughout the body. They innervate the skin, bone, muscle, most internal organs, blood vessels, and heart. Ironically, nociceptors are generally absent from the brain substance itself, although they are in the meninges.
Nociceptors vary in their selectivity. Mechanical nociceptors, some of which are quite selective, respond to strong pressure—in particular, pressure from sharp objects. A subset of nociceptors expresses Mas-related G protein–coupled receptor D (MrgprD); genetic ablation of just these neurons makes mice insensitive to noxious mechanical stimuli without affecting their responses to painful heat or cold. TRPA1 channels are involved in some forms of pain-related mechanosensation, and they may transduce stimuli that trigger pain originating from viscera such as the colon and bladder.
Thermal nociceptors signal either burning heat (above ~45°C, when tissues begin to be destroyed) or unhealthy cold; the heat-sensitive nociceptive neurons express the TRPV1 and TRPV2 channels, whereas the cold-sensitive nociceptors express TRPA1 and TRPM8 channels. A uniquely cold-resistant Na+ channel, Nav1.8, allows cold-sensitive nociceptors to continue firing action potentials even at temperatures low enough to silence other neurons.
Chemical nociceptors, which are mechanically insensitive, respond to a variety of agents, including K+, extremes of pH, neuroactive substances such as histamine and bradykinin from the body itself, and various irritants from the environment. Some chemosensitive nociceptors may express TRP channels that respond to, among other things, plant-derived irritants such as capsaicin (TRPV1), menthol (TRPM8), and the pungent derivatives of mustard and garlic (TRPA1).
Finally, polymodal nociceptors are single nerve endings that are sensitive to combinations of mechanical, thermal, and chemical stimuli. Nociceptive axons include both fast Aδ fibers and slow, unmyelinated C fibers. Aδ axons mediate sensations of sharp, intense pain; C fibers elicit more persistent feelings of dull, burning pain. The Na+ channel Nav1.7 has a particularly interesting relationship to pain. Patients with loss-of-function mutations of Nav1.7 are insensitive to noxious stimuli and experience repeated injuries because they lack protective reflexes. Several gain-of-function Nav1.7 mutations cause channel hyperexcitability and syndromes of intense chronic pain.
Sensations of pain can be modulated in a variety of ways. Skin, joints, or muscles that have been damaged or inflamed are unusually sensitive to further stimuli. This phenomenon is called hyperalgesia, and it can be manifested as a reduced threshold for pain, an increase in perceived intensity of painful stimuli, or spontaneous pain. Primary hyperalgesia occurs within the area of damaged tissue, but within ~20 minutes after an injury, tissues surrounding a damaged area may become supersensitive by a process called secondary hyperalgesia. Hyperalgesia seems to involve processes near peripheral receptors (Fig. 15-29) as well as mechanisms in the CNS.
FIGURE 15-29 Hyperalgesia of inflammation.
Damaged skin releases a variety of chemical substances from its many cell types, blood cells, and nerve endings. These substances—sometimes called the inflammatory soup—include neurotransmitters (e.g., glutamate, serotonin, adenosine, ATP), peptides (e.g., substance P, bradykinin), various lipids (e.g., prostaglandins, endocannabinoids), proteases, neurotrophins, cytokines, and chemokines, K+, H+, and others; they trigger the set of local responses that we know as inflammation. As a result, blood vessels become more leaky and cause tissue swelling (or edema) and redness (see Box 20-1). Nearby mast cells release the chemical histamine, which directly excites nociceptors.
By a mechanism called the axon reflex, action potentials can propagate along nociceptive axons from the site of an injury into side branches of the same axon that innervate neighboring regions of skin. The spreading axon branches of the nociceptors themselves may release substances that sensitize nociceptive terminals and make them responsive to previously nonpainful stimuli. Such “silent” nociceptors among our small Aδ and C fibers are normally unresponsive to stimuli—even destructive ones. Only after sensitization do they become responsive to mechanical or chemical stimuli and contribute greatly to hyperalgesia. For example, the neurotrophin nerve growth factor (NGF)—part of the inflammatory soup—triggers strong hypersensitivity to heat and mechanical stimuli by modulating TRPV1 channels. Activation of TRPA1 and ASICs are also important in hyperalgesia. The cytokine tumor necrosis factor-alpha (TNF-α) potentiates the inflammatory response directly and enhances release of substances that sensitize nociceptors. Drugs that interfere with neurotrophin and cytokine actions can be effective treatments for the pain of inflammatory diseases.
The cognitive sensations of pain are under remarkably potent control by the brain, more so than other sensory system. In some cases, nociceptors may fire wildly, although perceptions of pain are absent; on the other hand, pain may be crippling although nociceptors are silent. Chronic activation of nociceptors can lead to central sensitization, a chronic enhancement of central pain-processing circuits. Prolonged activity in nociceptive axons and their spinal cord synapses causes increased glutamate release, strong activation of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)– and NMDA (N-methyl-D-aspartate)–type glutamate receptors, and eventually a form of long-term potentiation (see pp. 329–337).
Nonpainful sensory input and neural activity from various nuclei within the brain can modify pain. For example, pain evoked by activity in nociceptors (Aδ and C fibers) can be reduced by simultaneous activity in low-threshold mechanoreceptors (Aα and Aβ fibers). This phenomenon is a familiar experience—some of the discomfort of a burn, cut, or bruise can be relieved by gentle massage or rubbing (stimulating mechanoreceptors) around the injured area. In 1965, Melzack and Wall proposed that this phenomenon involves a circuit in the spinal cord that can “gate” the transmission of nociceptive information to the brain; control of the gate could be provided by other sensory information (e.g., tactile stimulation) or by descending control from the brain itself. Gate-like regulation of pain may arise from the modulation of gamma-aminobutyric acid (GABA)–mediated and glycine-mediated inhibitory circuits in the spinal cord.
A second mechanism for modifying the sensation of pain involves the relatively small peptides called endorphins. In the 1970s, it was discovered that a class of drugs called opioids (including morphine, heroin, and codeine) act by binding tightly and specifically to opioid receptors in the brain and, furthermore, that the brain itself manufactures “endogenous morphine-like substances,” collectively called endorphins (see p. 315).
Muscle spindles sense changes in the length of skeletal muscle fibers, whereas Golgi tendon organs gauge the muscle's force
The somatic sensory receptors described thus far provide information about the external environment. However, the body also needs detailed information about itself to know where each of its parts is in space, whether it is moving, and if so, in which direction and how fast. Proprioception provides this sense of self and serves two main purposes. First, knowledge of the positions of our limbs as they move helps us judge the identity of external objects. It is much easier to recognize an object if you can actively palpate it than if it is placed passively into your hand so that your skin is stimulated but you are not allowed to personally guide your fingers around it. Second, proprioceptive information is essential for accurately guiding many movements, especially while they are being learned.
Skeletal muscles, which mediate voluntary movement, have two mechanosensitive proprioceptors: the muscle spindles (or stretch receptors) and Golgi tendon organs (Fig. 15-30). Muscle spindles measure the length and rate of stretch of the muscles, whereas the Golgi tendon organs gauge the force generated by a muscle by measuring the tension in its tendon. Together, they provide a full description of the dynamic state of each muscle. The different sensitivities of the spindle and the tendon organ are due partly to their structures but also to their placement: spindles are located in modified muscle fibers called intrafusal muscle fibers, which are aligned in parallel with the “ordinary” force-generating or extrafusal skeletal muscle fibers. On the other hand, Golgi tendon organs are aligned in series with the extrafusal fibers.
FIGURE 15-30 Golgi tendon organ and muscle spindle fibers. A muscle contains two kinds of muscle fibers, extrafusal fibers (ordinary muscle fibers that cause contraction) and intrafusal fibers (aligned in parallel with the extrafusal fibers). Some of the extrafusal fibers have Golgi tendon organs located in series between the end of the muscle fiber and the macroscopic tendon. The intrafusal fibers contain muscle spindles, which receive both afferent (sensory) and efferent (motor) innervation. The spindle (inset) contains both bag fibers, with nuclei bunched together, and chain fibers, with nuclei in a row.
The Golgi tendon organ consists of bare nerve endings of group Ib axons (see Table 12-1). These endings intimately invest an encapsulated collagen matrix and usually sit at the junction between skeletal muscle fibers and the tendon. When tension develops in the muscle as a result of either passive stretch or active contraction, the collagen fibers tend to squeeze and distort the mechanosensitive nerve endings, triggering them to fire action potentials.
The mammalian muscle spindle is a complex of modified skeletal muscle fibers (intrafusal fibers) combined with both afferent and efferent innervation. The spindle does not contribute significant force generation to the muscle but serves a purely sensory function. A simplified summary of the muscle spindle is that it contains two kinds of intrafusal muscle fibers (bag and chain), with two kinds of sensory endings entwined about them (the primary and secondary endings). The different viscoelastic properties of the muscle fibers make them differentially sensitive to the consequences of muscle stretch. Because the primary sensory endings of group Ia axons coil around and strongly innervate individual bag muscle fibers (in addition to chain fibers), they are very sensitive to the dynamics of muscle length (i.e., changes in its length). The secondary sensory endings of group II axons mainly innervate the chain fibers and most accurately transduce the static length of the muscle; in other words, they are slowly adapting receptors. The discharge rate of afferent neurons increases when the whole muscle—and therefore the spindle—is stretched. ENaC and ASIC2 channels may contribute to the stretch sensitivity of the sensory nerve terminals in muscle spindles.
What is the function of the motor innervation of the muscle spindle? Consider what happens when the α motor neurons stimulate the force-generating extrafusal fibers and the muscle contracts. The spindle, connected in parallel to the extrafusal fibers, quickly tends to go slack, which makes it insensitive to further changes in length. To avoid this situation and to continue to maintain control over the sensitivity of the spindle, γ motor neurons cause the intrafusal muscle fibers to contract in parallel with the extrafusal fibers. This ability of the spindle's intrafusal fibers to change their length as necessary greatly increases the range of lengths over which the spindle can work. It also means that the sensory responses of the spindle depend not only on the length of the whole muscle in which the spindle sits but also on the contractile state of its own intrafusal muscle fibers. Presumably, the ambiguity in this code is sorted out centrally by circuits that simultaneously keep track of the spindle's sensory output and the activity of its motor nerve supply.
In addition to the muscle receptors, various mechanoreceptors are found in the connective tissues of joints, especially within the capsules and ligaments. Many resemble Ruffini, Golgi, and Pacini end organs; others are free nerve endings. They respond to changes in the angle, direction, and velocity of movement in a joint. Most are rapidly adapting, which means that sensory information about a moving joint is rich. Nerves encoding the resting position of a joint are few. We are nevertheless quite good at judging the position of a joint, even with our eyes closed. It seems that information from joint receptors is combined with that from muscle spindles and Golgi tendon organs, and probably from cutaneous receptors as well, to estimate joint angle. Removal of one source of information can be compensated by use of the other sources. When an arthritic hip is replaced with a steel and plastic one, patients are still able to tell the angle between their thigh and their pelvis, even though all hip joint mechanoreceptors are long gone.