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The Somatosensory System II: Nociception, Thermal Sense, and Touch
One crucial role of the somatosensory system is to supply the brain with information related to insults that cause tissue damage. These signals ascend the neuraxis in a fiber bundle called the anterolateral system (ALS). Anyone who has used a hammer or hot skillet has had experience with this system. Hit your thumb with a hammer and, if you are lucky, only high-threshold mechanoreceptors that signal excess skin deformation will be activated. If you are unlucky, nociceptors that signal tissue damage will be recruited. Specifically, mechanonociceptors have been stimulated. One common response is to vigorously rub the damaged area. This activates central nervous system (CNS) pathways that decrease the transmission of nociceptive signals and alter the perception of pain.
After the hammer has done its damage, tissues release chemicals that activate another type of pain receptor, chemonociceptors. These receptors may contribute to the mechanism underlying long-term pain and tenderness ( hyperalgesia ). Similarly, the temperature of a skillet is detected by thermoreceptors in the skin and transmitted through the ALS. If a burn is produced, the tissue damage is signaled by high-frequency firing of thermonociceptors. ALS activation can lead to a variety of responses, including withdrawal reflexes, the conscious perception of pain, emotional effects such as suffering, and behavioral changes aimed at avoiding the cause of the pain.
Overview
Nondiscriminative ( poorly localized ) touch, innocuous thermal, and nociceptive ( mechanical, chemical , and thermal ) and itch sensations (from the body, back of the head, and visceral structures) are conveyed by bundles of fibers that collectively make up the ALS. This system transmits signals originating in peripheral receptors to spinal cord and brainstem neurons ( Fig. 18.1 ). These signals are then relayed to lateral and medial thalamic nuclei and from there to the trunk and extremity representations in the primary and secondary somatosensory cortex and limbic cortex. The anterior trigeminothalamic pathway ( Fig. 18.1 ; see also Figs. 18.17 and 18.18 ) carries similar signals that originate from receptors in the face, oral cavity, teeth, and front of the head. These are relayed through brainstem and thalamic nuclei to face areas of the sensory cortex. The touch fibers of the ALS differ from those described for the posterior column–medial lemniscal system (PCMLS) (see Chapter 17 ) in several ways: (1) they yield a generalized feeling of being touched but do not give precise localization, (2) their receptive fields are larger, and (3) they are smaller in diameter and more slowly conducting. Disruption of the ALS can produce symptoms ranging from reduced sensibility ( hypesthesia ), to numbness, tingling, and prickling ( paresthesia ), to a complete loss of sensibility ( anesthesia ).
Anterolateral System
Fibers within the lateral spinothalamic tract were considered to carry only pain and thermal information, whereas the anterior spinothalamic tract was thought to be concerned only with nondiscriminative touch. This older view of separate tracts conveying separate modalities of sensory information is not used in this chapter. Current thinking holds that all parts of the ALS carry all modalities (pain, temperature, and touch) but that there are direct and indirect pathways for this information to reach the brain. The direct pathway is the neospinothalamic pathway (spinal cord → lateral thalamus → somatosensory cortices), and the indirect pathway is the polysynaptic paleospinothalamic pathway (spinal cord → reticular formation → medial thalamus → cingulate, frontal + limbic cortices). Both of these pathways, plus other ascending fibers as defined later, collectively form the ALS.
The ALS is a composite bundle that includes spinothalamic, spinomesencephalic, spinoreticular, spinobulbar, and spinohypothalamic fibers. Spinothalamic fibers project directly from the spinal cord to the ventral posterior nuclei (ventral posterolateral [VPL] and ventral posterior inferior [VPI] nuclei) and the posterior nuclear group (including the ventral medial nucleus VMpo) of the thalamus. Collaterals to the reticular formation arise from some of these axons. Spinomesencephalic axons project to the periaqueductal gray (PAG) and to the tectum; the latter are spinotectal fibers. Although spinoreticular fibers project to the reticular formation of the medulla, pons, and midbrain, collaterals may ascend as reticulothalamic fibers to other targets, such as the intralaminar and dorsomedial nuclei of the thalamus. Thus ascending axons originating in the spinal cord can have multiple collaterals terminating in different locations throughout the brainstem. Spinohypothalamic fibers terminate in hypothalamic areas and nuclei, including some that give rise to hypothalamospinal axons. Projections of less relevance to the somatosensory system, such as spinoolivary fibers, are grouped under the category of spinobulbar fibers.
Cutaneous Nociceptors and Primary Neurons
The receptors for nondiscriminative touch, innocuous thermal stimuli, and nociceptive stimuli are distributed in glabrous and hairy skin as well as in deep tissues, including muscles, joints, blood vessels, and viscera ( Fig. 18.2 and Table 18.1 ). Morphologically, these receptors are all free nerve endings ( Fig. 18.2 ); that is, they lack specialized receptor cells or encapsulations. The basis for their submodality specificity likely depends upon a unique array of membrane receptor complexes (e.g., ionotrophic [ligand-gated ion channels] glutamate receptors [iGluRs] or metabotropic [G protein–coupled] glutamate receptors [mGluRs]).
Table 18.1
Classification of Cutaneous Mechanical, Thermal, and Nociceptive Receptors by Small-Diameter Fibers and Their Adequate Stimuli
| Receptor | Adequate Stimulus |
|---|---|
| Cutaneous Mechanoreceptors | Respond to nondiscriminative tactile stimuli |
| Aδ and C fiber high-threshold mechanoreceptors | Pinch, rub, stretch, squeeze |
| Cutaneous Thermoreceptors | Respond to transient changes in temperature |
| Warm and cool thermoreceptors | Innocuous warm and cool stimuli |
| Cutaneous Nociceptors | Mediate cutaneous pain |
| Aδ mechanonociceptors | Mechanical tissue damage |
| C-polymodal nociceptors | Mechanical tissue damage, noxious thermal stimuli, algesic compounds |
| Other Cutaneous Nociceptors | Mediate cutaneous pain |
| C fiber mechanonociceptors | Mechanical tissue damage |
| Aδ, heat thermonociceptors | Noxious thermal stimuli, tissue damage (?) |
| Aδ, C fiber cold thermonociceptors | Noxious thermal stimuli, tissue damage (?) |
| C fiber chemonociceptors | Algesic compounds |
Nonetheless, these submodalities are transduced by activation of peripheral branches of either thinly myelinated Aδ (A-delta) fibers or unmyelinated C fibers. The density of free nerve endings and the corresponding size of receptive fields vary over the body surface in the same way as for other cutaneous receptors (see Fig. 17.3 ), being highest on the hands and in the perioral area. Regardless of size or location, however, each field is exquisitely sensitive to thermal, chemical, or mechanical stimuli.
Nondiscriminative touch results from the stimulation of free nerve endings that act as nonnoxious high-threshold mechanoreceptors ( Table 18.1 ). These receptors respond to any rough stimulus, including tapping, squeezing, rubbing, and stretching of the skin, that does not result in tissue damage ( Fig. 18.3 A ). Nerve fibers associated with these receptors generally have no background activity when they are unstimulated; when they are stimulated, they respond with a sustained discharge that signals stimulus duration ( Fig. 18.3 A ).
Nonnociceptive thermoreceptor s fall into two classes: those activated by warmth (35° C to 45° C) and those activated by cooling (17° C to 35° C). They show a graded response to changes in ambient temperature ( Fig. 18.3 B ). With repeated stimulation, these receptors become sensitized and have a decreased activation threshold and a larger response to the application of a stimulus.
Nociceptors are found in cutaneous as well as in deep structures. Two major classes of cutaneous nociceptors have been identified. They are the Aδ mechanical nociceptors and C-polymodal nociceptors. These receptors are found at the end of peripheral processes of thinly myelinated (Aδ) or nonmyelinated (C) fibers ( Fig. 18.2 and Table 18.1 ). The cutaneous receptive field of an Aδ nociceptor consists of a number of small sensitive spots (2 to 30) scattered over an area of skin. Each spot ranges from 50 to 180 μm in diameter. Aδ mechanical nociceptors respond to mechanical injury accompanied by tissue damage. C-polymodal nociceptors respond to mechanical, thermal, and chemical stimuli. The cutaneous receptive field of a C-polymodal nociceptor usually consists of one or two sensitive spots, with each spot covering an area of skin 1 to 2 mm 2 . For a comparable region of skin, the C fiber spots are larger but fewer in number than the Aδ spots, which are smaller but more numerous.
Other cutaneous receptors that respond to high-threshold or noxious stimuli have been identified. They include receptors that respond to extreme temperature changes (thermonociceptors) ( Table 18.1 ) and receptors that respond to chemicals, irritants, or algesic (pain-producing) compounds (chemonociceptors) ( Table 18.1 ). Extreme heat (>45° C) or cold (<17° C) that burns or freezes the skin produces high-frequency firing in both Aδ and C thermonociceptors ( Fig. 18.3 B ). C fiber chemonociceptors ( Table 18.1 ) are activated by the release of endogenous substances associated with tissue damage and inflammation, such as bradykinin and hydrogen ions, and foreign irritants such as insect venoms.
Transient Receptor Potential Channels and Thermal Sensations
Specialized surface membrane receptors called transient receptor potential (TRP) channels have recently been identified in cutaneous Aδ and C thermonociceptors. Several of these channels respond to application of either noxious heat or noxious cold. The most common of these receptors, the capsaicin receptor TRPV1, is activated by capsaicin (the active ingredient of chili peppers), noxious temperatures (>43° C), and protons. A second channel, the TRPV2 receptor, is activated by high intensities of noxious heat (>52° C). The cold receptor TRPA1 responds to very low temperatures (<16° C) and some chemical substances. When activated, these receptors can signal thermal pain.
Nonnociceptive thermal stimuli activate TRP channels in Aδ and C thermoreceptors. Warm thermoreceptors express TRP3 (>33° C) and TRP4 (24° C to 34° C) receptors. Cold thermoreceptors express TRPM8 (<23° C) receptors, which respond to cooling and menthol. Activation of these receptors can signal the range of innocuous thermal sensations.
Peripheral Sensitization and Primary Hyperalgesia
Nociceptors, unlike Meissner corpuscles or Merkel cells, demonstrate a unique phenomenon called sensitization. After an insult, these receptors become more sensitive (lower activation threshold) and thus more responsive (increases in firing rate) to noxious stimulation within their receptive fields. Although the mechanisms responsible for receptor sensitization are not completely known, irritating chemicals (capsaicin), inflammatory mediators (bradykinin, prostaglandins), and neurotransmitters (serotonin, histamine, norepinephrine) released from damaged skin or by-products from plasma, or both, are thought to contribute to this phenomenon. As a result of this heightened sensitivity, the affected area is exquisitely sensitive to painful stimuli, and patients experience a sensory disturbance called hyperalgesia (exaggerated response to a painful stimulus). This condition can be differentiated into primary hyperalgesia and secondary hyperalgesia. Primary hyperalgesia occurs in the region of damaged skin and is probably the result of receptor sensitization. Secondary hyperalgesia occurs in the skin immediately bordering the damaged tissue. Although receptor sensitization may contribute to secondary hyperalgesia, there is likely to be a central (e.g., spinal) component as well.
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