THE SOMATOSENSORY SYSTEM
Cutaneous and deep receptors
Type of receptors. In the skin: free and encapsulated receptors according to their structures. Functionally, skin receptors can be classified by their adequate stimulus as mechanoreceptors, thermoreceptors, and nociceptors.
Nociceptors are free receptors. Functionally, skin nociceptors are high-threshold mechanoreceptors or polymodal receptors. Axons responding to mechanical stimulus only if it is very intense. Most of them are in the Adelta range (15-30m/sec). Almost half of the unmyelinated axons of peripheral nerve respond well not only to intense mechanical stimuli, but also to heat and noxious chemicals. Axons of these polymodal nociceptors make up the majority of very slowly conducting (1m/s) C fibers in a peripheral nerve. Their receptors respond to minute punctures of the epithelium, with a response magnitude that depends on the degree of tissue deformation. They also respond to temperatures in the range of 40-60oC and change their response rates as a linear function of warming (in contrast with the saturating responses displayed by non-noxious thermoreceptors at high temperatures). The relatively rapidly conducting Adelta and the slowly conducting C fibers are responsible for two very different qualities of pain. The rapidly transmitted signal, often with high spatial resolution is called first pain or cutaneous pricking pain. It is well localized and easily tolerated (fast conducting Adelta fibers). The much slower, highly affective component is called second pain or burning pain (poorly localized and poorly tolerated). The third or deep pain, arising from viscera, musculature and joints. It is poorly localized, can be chronic and often associated with referred pain.
Thermoreceptors. According to combined physiological and histological analysis the free endings are also responsible for the perception of heat and cold. Specific thermoreceptors respond with a sustained response over a narrow range of skin temperature but do not respond to skin indentation. Axons of warm receptors are unmyelinated, slowly conducting C fibers, whereas axons of cold receptors are lightly myelinated, mostly Adelta fibers. Thermoreceptors are very poor indicators of absolute temperature but are very sensitive to changes in skin temperature.
Mechanoreceptors can be free receptors, for example, those found at the roots of hairs, or encapsulated ones such as those in the glabrous[hairless] skin (e.g.Meissner and Pacinian corpuscles: rapidly adapting [RA]; Ruffini corpuscles and Merkel's disks: slowly adapting[SA]).
Sensory information from Meissner corpuscles and RA afferents leads to adjustment of grip force when objects are lifted. These afferents respond with a brief burst of action potentials when objects move a small distance during the early stages of lifting. In response to RA afferent activity, muscle force increases reflexively until the gripped object no longer moves. Such a rapid response to a tactile stimulus is a clear indication of the role played by somatosensory neurons in motor activity.
Activating Merkel's disks and the SA axons terminating in them are responsible for form and texture perception. As would be expected for receptors mediating form perception, Merkel disks are present at high density in the digits and around the mouth (50/mm2 of skin surface) at lower density in other glabrous surfaces and at very low density in hairy skin. This innervations density shrinks progressively with the passage of time so that by the age of 50, the density in human digits is reduced to 10/mm2. SA axons contacted by Merkel cells display, low threshold responses to cutaneous stimuli. Unlike RA axons, SA fibers respond not only to the initial indentation of skin, but also to sustained indentation up to several second in duration.
Stimulating axons that appear to end in Pacinian corpuscles gives a feeling of vibration. Sensory axons at the core of Ruffini corpuscles display slowly adapting responses to the latareal movement or stretching of skin.
Proprioceptors. The term proprioceptive or kinesthetic sense is used to refer to the perception of joint position, joint movements, and the direction and velocity of joint movement. There are numerous mechanoreceptors in the muscles, the muscle fascia, and in the dense connective tissue of joint capsules and ligaments. There are two specialized encapsulated, low-threshold mechanoreceptors: the muscle spindle and the tendon organ (Golgi). Their adequate stimulus is stretching of the tissue in which they lie.
Muscle spindles, joint and skin receptors all contribute to kinesthesia. Muscle spindles appear to provide their most important contribution to kinesthesia with regard to large joints, such as the hip and knee joints, whereas joint receptors and skin receptors may provide more significant contributions with regard to finger and toe joints.
Muscle Spindle and the golgi tendon organ (stretch receptors)
Scattered throughout virtually every striated muscle in the body are long, thin, stretch receptors called muscle spindles. They are quite simple in principle, consisting of a few small muscle fibers with a capsule surrounding the middle third of the fibers. These fibers are called intrafusal fibers, in contrast to the ordinary extrafusal fibers. The ends of the intrafusal fibers are attached to extrafusal fibers, so whenever the muscle is stretched, the intrafusal fibers are also stretched. The central region of each intrafusal fiber has few myofilaments and is non-contractile, but it does have one or more sensory endings applied to it. When the muscle is stretched, the central part of the intrafusal fiber is stretched, and each sensory ending fires impulses.
Numerous specializations occur in this simple basic organization, so that in fact the muscle spindle is one of the most complex receptor organs in the body. Only three of these specializations are described here; their overall effect is to make the muscle spindle adjustable and give it a dual function, part of it being particularly sensitive to the length of the muscle in a static sense and part of it being particularly sensitive to the rate at which this length changes.
1. Intrafusal muscle fibers are of two types. All are multinucleated, and the central, non-contractile region contains the nuclei. In one type of intrafusal fiber, the nuclei are lined up single file; these are called nuclear chain fiber. In the other type, the nuclear region is broader, and the nuclei are arranged several abreast; these are called nuclear bag fibers. There are typically two or three nuclear bag fibers per spindle and about twice that many chain fibers.
2. There are also two types of sensory endings in the muscle spindle. The first type, called the primary ending, is formed by a single Ia (A-alpha) fiber, supplying every intrafusal fiber in a given spindle (although it innervates the bag fibers more heavily than the chain fibers). Each branch wraps around the central region of the intrafusal fiber, frequently in a spiral fashion, so these are sometimes called annulospiral endings. The second type of ending is formed by a few smaller nerve fibers (II or A-Beta) on both sides of the primary endings. These are the secondary endings, which are sometimes referred to as flower-spray endings because of their appearance. Primary endings are selectively sensitive to the onset of muscle stretch but discharge at a slower rate while the stretch is maintained. Secondary endings are less sensitive to the onset of stretch, but their discharge rate does not decline very much while the stretch is maintained. In other words, both primary and secondary endings signal the static length of the muscle (static sensitivity) whereas only the primary ending signals the length changes (movement) and their velocity (dynamic sensitivity). The change of firing frequency of group Ia and group II fibers can then be related to static muscle length (static phase) and to stretch and shortening of the muscle (dynamic phases).
3. Muscle spindles also receive a motor innervation. The large motor neurons that supply extrafusal muscle fibers are called alpha motor neurons, while the smaller ones supplying the contractile portions of intrafusal fibers are called gamma neurons. Gamma motor neurons can regulate the sensitivity of the muscle spindle so that this sensitivity can be maintained at any given muscle length.
Presumably, there are two types of efferent gamma neurons. One consists of gamma-dynamic cells innervating predominantly the intrafusal-bag fibers. The other represent gamma-static cells predominantly stimulating the intrafusal nuclear chain-fibers.
The Golgi tendon organ. Is located at the musculotendinous junction. There is no efferent innervation of the tendon organ, therefore its sensitivity cannot be controlled from the CNS. The tendon organ, in contrast to the muscle spindle, is coupled in series with the extrafusal muscle fibers. Both passive stretch and active contraction of the muscle increase the tension of the tendon and thus activate the tendon organ receptor, but active contraction produces the greatest increase. The tendon organ, consequently, can inform the CNS about the muscle tension. In contrast, the activity of the muscle spindle depends on the muscle length and not on the tension. The muscle fibers attached to one tendon organ appear to belong to several motor units. Thus the CNS is informed not only of the overall tension produced by the muscle but also of how the workload is distributed among the different motor units.
Joint receptors. The joint receptors are low-threshold mechanoreceptors and have been divided into four groups. They signal different characteristics of joint function (position, movements, direction and speed of movements). The free receptors or type 4 joint receptors are nociceptors.
Primary Sensory Fibers and Neurotransmitters
Afferent fibers from the receptors follow the peripheral nerves toward the CNS. The sensory fibers of the spinal nerves have their perikarya in the dorsal root ganglia. Likewise, the sensory fibers in the cranial nerves have their perikarya in ganglia close to the brain stem. The ganglion cells are pseudounipolar and send one long process peripherally, ending freely or in encapsulated sense organs. The central process enters the cord and then divides into an ascending and a descending branch. These branches give off several collaterals ventrally to the gray matter of the cord. The different kinds of sensory receptors are supplied with axons of characteristic thickness. Impulses from low-threshold mechanoreceptors are, for example, conducted in the thick myelinated fibers (A alfa and A beta). Impulses from cold receptors are conducted in thin myelinated fibers (A delta), whereas unmyelinated (C) fibers conduct from heat receptors. Impulses from nociceptors are conducted in A delta and C fibers. In the spinal cord, the termination of A delta and C fibers are almost completely separated from those of the A alfa and A beta fibers.
The most likely candidate for dorsal root neurons is the excitatory amino acid transmitter glutamate. Several neuropeptides have been demonstrated in the perikarya of spinal ganglion cells, such as substance P, VIP, cholecystokinin, somatostatin, calcitonin gene related peptide (CGRP), galanin and others. The functions of these peptides are largely unknown, but they presumably mediate slow, modulatory synaptic actions in the dorsal horn. Neuropeptides present in the peripheral ramifications of primary sensory neurons are involved in axon reflex.
Dorsal Column-Medial Lemniscus System
This pathway is important for touch, pressure, vibration and kinesthesia. The thick dorsal root fibers, conducting impulses from the low-threshold, rapidly adapting mechanoreceptors of the skin, muscles and joints, ascend in the dorsal column to terminate in the gracile and cuneate nuclei. As the fibers ascend in the dorsal columns, they send off collaterals ventrally to the spinal gray matter. Most of these collaterals terminate on interneurons, but some reach as far as the ventral horn motorneurons. Pathways from the face are carried through the lemniscus trigeminalis. Fibers form the spinal cord end in the thalamic ventroprosterolateralis (VPL) and from the lemniscus trigeminalis in the thalamic VPM. Fribers from the VPL and VPM terminate in the primary somatosensory (SI) cortex. In addition, some fibers from the VPL and VPM end in the secondary somatosensory area (SII), situated in the upper wall of the lateral cerebral fissure.
Experiments with cutting of the dorsal columns in monkeys and observations in humans with damage more or less limited to the dorsal columns indicate that the dorsal column-medial lemniscus system is important in spatial and temporal comparisons of stimuli, that is the discriminative sensation. Such sensory information is of crucial importance for the performance of many voluntary movements. Indeed, most studies indicate that damage to the dorsal columns produces severe ataxia.
The Spinothalamic Tract (anterolateral system)
The spinothalamic tract is of primary importance for the perception of pain and temperature. A relatively crude sense of touch and pressure can also be mediated by this pathway The A-delta fibers terminate in LI and V, while the C fibers in LII. Spinothalamic cells are located in LI, IV-V, VII and VIII. Most thin dorsal root fibers do not synapse directly onto spinothalamic cells but rather influence them indirectly via spinal interneurons. Interneurons of the dorsal horn, especially those of the substantia gelatinosa, have a decisive role on whether the signals from nociceptors will be transmitted to higher levels of the nervous system.The spinothalamic cells in the cord can be classified by their response properties: 1) low threshold units - cells that react only to light mechanical stimuli (light touch of the skin); 2) wide dynamic range units (WDR) - cells that react to stimuli of high intensity (activating nociceptors) and to light stimuli. The impulse frequency of these cells increases with increasing stimulus intensity; 3) high-threshold units - cells that respond only to stimuli of an intensity sufficient to activate nociceptors, and 4) thermosensitive units.
Thalamic termination sites: VPL,
Additional Pathways for Transmission of Somatosensory Information
Spinocervicothalamic tract: primarily from neurons located in LIV there is a projection through the lateral cervical nucleus (located on the lateral aspect of the posterior horn in the uppermost part of the cervical cord)-contralateral VPL. This pathway apparently transmit signals from hair receptors. The fibers ascend in the dorsolateral fasciculus. Position sense from the leg is primarily located in the dorsolateral funiculus. The fibers (spinomedullary) terminate close to the gracile nucleus. Axons from this cell group cross the other side of the medulla and join the medial lemniscus.
Spinoreticulothalamic tract: Neurons from LVII-VIII terminate in the reticular formation (RF). Many of the neurons in the RF from here project to terminate in the intralaminar thalamic nuclei of both sides. The pathway lacks somatotopic organization. It has been assumed that it is of particular importance for emotional, affective aspects of pain perception.
Central Control of Sensory Transmission
There are descending fiber connections from the cerebral cortex and the brain stem ending in various relay nuclei of the somatosensory pathways. These connections are somatotopically organized and enable selective control of sensory signal transmission from particular parts of the body and from particular receptor types. Among the various aspects of central control of sensory impulse transmission, those related to pain in particular have received much attention in recent years. According to one hypothesis, the periaqueductal gray (PAG) stimulation through connections to the nucleus raphe magnus (NRM) and hence to the cord could elicit inhibition of spinothalamic cells so that they are less readily activated by impulses from nociceptors. Part of the analgesia is mediated through the binding of opiates to their receptors in the PAG, the NRM and parts of the spinal cord (LI, II and V). Microinjection of morphine in the PAG can produce analgesia in experimental animals that depend at least partly on connections from NRM to the spinal cord. The transmitter of fibers from the raphe magnus is serotonin. Also some of the dorsal horn interneurons contain opioid peptides. Suppression of pain may enable continuation of intense physical activity for a while, which may be of vital importance. Also analgesia may also be produced by stimulation of peripheral nerves (acupuncture) or in stressful situations. Depending on the nature of the stress, the analgesia may be mediated by liberation of endorphins or by apparently endorphin independent mechanisms. There is also evidence to suggest that the emotional state of the animal is of importance for whether analgesia is produced or not.
The Somatosensory Cortical Regions
Sensory impulses conducted in the medial lemniscus and the spinothalamic tract finally reach the two somatosensory areas, SI and SII. Both of these cortical regions receive somatotopically organized projections from the VPL and VPM. Somatosensory impulses also reach other cortical regions, such as the motor cortex (M1). Within each of the cytoarchitectonic subdivisions (areas 3a, 3b, 1, 2) of the primary sensory cortex it appears that the whole body has its representation; thus there are probably four body maps within S1.
The body maps contain many distortions, the most dramatic of which are the greatly enlarged representations of the hand, particularly the digits and that of the face. Representations of the digits occupies more than 100 times the cortical surface area devoted to the trunk. By this relative enlargement in cortical representation, the digits and lips are said to be magnified, and the degree of overrepresentation is called the magnification factor.
Neurons in area 3b and area 1 are primarily activated by stimulation of cutaneous receptors. In contrast, areas 3a and area 2 are responsive to deep stimuli, with area 3a particularly responsive to muscle afferents and area 2 to joints. Even though many neurons in SI are activated only or most easily from one receptor type -that is, they are modality-specific -there are also neurons in SI with more complex properties. In an fMRI study in humans (Moore et al., 2000), tactile task activated areas identified by the authors as areas 3b and 1, while motor/kinaesthetic task also activated regions deep in the postcentral gyrus consistent with the putative location of area 3a.
SII is located in the upper bank of the lateral sulcus within the parietal operculum. Receive input from SI. Neurons of SII, in turn, give rise to axons that innervate the insular cortex and from there somatosensory information reaches the perirhinal cortex and the amygdala. By this scheme, SII is vital as the obligatory route taken by sensory inputs mediating tactil learning and memory. A second major role for SII apparent from its intracortical connectivity is that of sensory-motor integration. In monkeys, at least 3 separate somatosensory representation have been found in SII, though surfaces are represented at a coarser grain than in anterior parietal regions (SI) and large proportion of the units responsive to bilateral stimulation of skin sites. It has been speculated that such bilateral responsiveness facilitates the integration of information between hands for tasks requiring bimanual coordination. Studies have also found that the responses of neurons in SII area are modulated by attentional state of the animal.
Cortical Map Plasticity (Ramachandran, Merzenich)
Further Processing of Sensory Information:
The posterior parietal cortex Areas 5 and 7 belongs to the so-called association areas of the cortex. They do not receive direct sensory information from the large somatosensory pathways but via numerous association fibers from SI and SII. Most electrophysiological recording studies have stressed the complexity of single and multiunit responses. Recording in area 5, for example, some units responded to stimulus conjuction, such as simultaneous skin and joint stimulation. The activity of neurons in area 5, and 7 may depend not only on what is occurring in the periphery but also on whether the attention of the monkey is directed toward the actual stimulus. Area 5 has been identified as a higher order somatosensory association region that is involved in planning movements that require visual guidance or as a command area required to match appropriate motor responses to sensory inputs. Area 7a and 7b seem to code the locations of external objects or body parts in space, although there is a controversy whether the coordinate systems used by these neurons are head- torso or eye-centered.
There is a controversy whether or not parallel or serial processing is used in somethesis by the human cortex. EEG and MEG support a serial processing scheme, with anterior parietal activity present as early as 20 ms after the delivery of tactile stimuli and lateral sulcal sources peaking in the 100-180 ms range. There is some evidence from MEG, however, that under certain conditions anterior parietal neurons and lateral sulcal neurons contralateral to a tactile stimulus may be active concurrently around 20-30 ms after the stimulus.
In somesthesis, similar to vision, it is suggested (Mishkin, 1979) that information is segregated into a dorsal stream (‘where’) and a ventral system (what), although it is not as clear-cut in the somatosensory system as in the visual one. Lesion to the dorsomedial cortex (including the SMA, and medial BA5, BA7) resulted in the disruption of the somesthetic processing per se, whereas ventrolateral lesions (around the lateral sulcus) were more likely to disrupt tactile object recognition (Caselli, 1993). A hierarchical processing scheme for somesthesis was suggested by Bodegard et al (2000, 2001). Accordingly, BA3b and BA1 active indiscriminately to all forms of tactile stimuli, BA2 showing differential responses when subjects had to distinquish surface curvatures and the posterior parietal regions being specifically active during the active and passive shape discrimination task, which the authors interpret as being selectively involved in the processing of global object shape.
Finally, imaging studies suggest that higher visual areas may also play a role in some aspect of tactile processing in the human brain and play a functional role in Brail reading in the blind (Sadato et al., 1999). In an fMRI study it has been demonstrated, that an occipitotemporal region (from posterior fusiform gyrus to post inf temporal sulcus) responded equally well to visually presented objects as haptically explored obejcts