Features of Sensory Systems Receptors
Afferent (First-Order) Neurons
Pathways From the Body, Limbs, and Back of Head
Major Classes of Functionally Defined Neurons and the Spinothalamic Tracts Wall’s Concept of Pain in Target Motor Responses
Pathways From the Anterior Head Temperature (Thermal) Sense Perception of Pain
The Gate Control Theory of Pain Modulation
Descending Control Mechanisms of Pain Modulation Endogenous Pain Control
Referred (Transferred) Pain
Stimulus-Induced and Stressed-Induced Analgesia Central Pain Syndrome (Thalamic Syndrome) Phantom Limb Sensation
Somatotopic Organization of the Lateral Spinothalamic Tract
155
detectors in humans.) The specificity of each modality is maintained within the nervous sys-tem by being segregated into discrete anatomi-cal pathways and processing centers. As a schema, every general sensory system consists of a core sequence of primary afferent fibers, relay nuclei located in the spinal cord, brain-stem, and thalamus, together with interconnec-tions and culminating at the cerebral cortex.
Each processing nucleus not only consolidates inputs from adjacent receptors but also inte-grates signals from inhibitory neurons and descending projections to transform and enhance the sensory information (see Fig. 3.13).
The nervous system responds to stimuli from a variety of environmental energies that are sensed by receptors associated with each modality. The recipient information is transmit-ted by neurons with their cell bodies locatransmit-ted in the dorsal root ganglia or its equivalent ganglia in the cranial nerves to neurons within the cen-tral nervous system (CNS). The receptor for each modality has a singular morphological and functional specialization that monitors a specific type of environmental stimulus.
Pain sensations are mediated by nociceptors (free nerve endings) that are stimulated by tissue-damaging impacts such as pinching or injury and chemical substances released from tissue cells physically damaged or injured from extreme heat or cold resulting from burns and frostbite (Chap. 9). Temperature is sensed by naked nerve endings of unmyelinated or lightly myelinated nerve fibers. These endings sense what is then processed into the everyday per-ceptions of cool, cold, warmth, and hot sensa-tions. Discriminative touch is a mental response to signals from encapsulated recep-tors sensitive to physical distortions, indenta-tions, and movements across the skin (Chap.
10). Proprioception refers to stretch or contrac-tions of muscles and joint movements involv-ing the head, trunk, and limbs (Chap. 10).
Spatial resolution, mediated by mechanorecep-tors, is most accurate on the fingertips and lips, where these sensors are most abundant. Propri-oceptors utilize pressure and motion to sense the shape and surface texture of objects handled.
FEATURES OF SENSORY SYSTEMS The term sensory is used to include all affer-ent input from the peripheral nerves, whether consciously perceived or not. Sensations are conscious perceptions and experiences associ-ated with stimuli arising directly from the stim-ulation of receptors of the sense organs. The sensory systems are involved in (1) the aware-ness of sensations, (2) the unconscious inputs that underlie the control of movements and many bodily functions, and (3) neural activities associated with arousal. The sensory systems have evolved to provide information from both the internal and external environments of the organism. Receptors are the monitors sensing the environment. They are involved with trans-duction, which is the conversion of stimulus energy into neural activity. The quality of each stimulus results in a form of sensation called a modality, such as pain, thermal sense, touch, or vision. Each modality has submodalities (e.g., vision—perceptions of color, form, depth, and motion). The three receptor types and some associated modalities are (1) mechanoreceptors such as temperature (thermal), noxious (pain or nociceptors), auditory (sound) and touch recep-tors. (2) chemoreceptors (taste and smell) and (3) photoreceptors (light). Transduction in a mechanoreceptor is brought about by the direct mechanical interaction of a stimulus with the channels on a receptor membrane. In an unstimulated membrane, only a few channels are open. When the receptor membrane is deformed by a stimulus, more channels open and Na+and K+shift to produce depolarization, called the receptor potential. Transduction in a chemoreceptor results from the interaction of a chemical with a receptor linked to a second-messenger system to mediate channel open-ings. This is the means utilized by olfactory receptors and certain gustatory receptors. The transduction in a photoreceptor is associated with absorption of light by the membranous disks of the rods and cones of the retina. The resulting change in receptor membrane perme-ability involves a second-messenger system.
Four distinct elementary general somatic modalities are recognized: (1) pain elicited by noxious stimuli in damaged tissue (Chap. 9), (2) thermal sensations elicited by warm and cool stimuli, (3) touch elicited by mechanical stimuli applied to the body (Chap. 10), and (4) proprioceptive sensations elicited by the mechanical displacement of muscles and joints (Chap. 10).
Two major general sensory systems are associated with sensory input from the spinal nerves from the body. Equivalent systems are associated with similar input from the head (e.g., from the trigeminal nerve). They are (1) the anterolateral system of pathways for pain and temperature and somewhat for touch and (2) the dorsal column–medial lemniscal sys-tem of pathways for touch and proprioception (Chap. 10). Each of the systems is organized (1) with most of the sensory submodalities conveyed by functionally separate pathways, (2) hierarchically with successive serial pro-cessing centers (called relay nuclei) terminat-ing at the cerebral cortex, and (3) for parallel processing at each level (Chap. 3). These two systems and their pathways converge on dis-tinct and separate populations of neurons within the ventral posterior nucleus of the thalamus. From the thalamus, neural informa-tion is projected to the sensory areas of the cerebral cortex, where the various submodali-ties are integrated into the experience of per-ception. It is at these higher centers that the several aspects of sensations are finely honed, including (1) quality (e.g., pain), (2) intensity, (3) location on body, (4) duration, and (5) affect (e.g., range from pleasant to unpleas-ant). It is these attributes that make a percep-tion more than a sensapercep-tion.
The pathways of the general sensory sys-tems usually consist of a sequence of first-order, second-first-order, and third-order neurons.
The first-order neurons are those peripheral sensory neurons with cell bodies in spinal dor-sal root ganglia, or cranial nerve ganglia, and axons that terminate in the spinal cord or brain-stem. Second-order neurons are those with cell bodies in the nuclei of the spinal cord and/or
brainstem with axons that ascend to terminate in the thalamus. An assembly of axons of second-order neurons is called a tract (fascicu-lus or pathway) in the white matter of the spinal cord and could be called a lemniscus (ribbon) in the brainstem. Third-order neurons are those with cell bodies in the thalamus and axons that terminate in the somatosensory cortex (areas 3, 1, and 2) of the parietal lobe.
The centers and nerve fibers involved with the processing and transmission of signals resulting in the conscious appreciation of pain and temperature are in such close proximity that their pathways are collectively called the pain and temperature pathways.
RECEPTORS
Receptors have been variously classified.
Exteroceptors, located near the body surface, are generally stimulated by external environ-mental energies. They are sensed as touch, light touch, pressure touch, pain (noxious stimuli), temperature, odor, sound, taste, or light. Proprioceptors are located within deep structures of the head, body wall, and extrem-ities. Proprioception includes such modalities as position sense, vibratory sense, balance, and sense of movement. Interoceptors monitor the viscera and project information sensed as cramps, pain, and fullness and are utilized in visceral reflexes (e.g., carotid sinus reflex).
Mechanoreceptors respond to mechanical stimuli (touch, hearing). Chemoreceptors respond to chemical stimuli (taste, smell).
Chemesthesis is now recognized as a common chemical sense comprising irritant-detecting receptors, resembling pain receptors (nocicep-tors), that are sensitive to chemicals applied to the skin, mucosal membranes of the oral cav-ity, nasal cavities, respiratory tract, and genital orifices. The free nerve endings that respond to chemicals including irritants do not constitute a separate, independent sense, but, rather, are part of the general somatic nervous system.
The chemosensitive fibers appear to be a sub-set of pain and temperature fibers.
Thermore-Chapter 9 Pain and Temperature 157
ceptors (temperature receptors) respond to various degrees of warmth and cold.
Peripheral Pain Mechanisms
Receptors of “painful” stimuli are collec-tively referred to as nociceptors. They are free (naked) nerve endings that respond to direct stimulation and to chemical products associ-ated with local injury (noxious stimuli) (see Figs. 10.1 and 10.2). Three types of free nerve ending receptor are associated with two types of afferent fiber. On the basis of functional cri-teria, they are (1) mechanosensitive nocicep-tors with A-delta fibers, (2) mechanothermal nociceptors with A-delta fibers, and (3) poly-modal nociceptors (respond to thermal, mechanical, thermal, and chemical stimuli)
with C fibers (see Fig. 9.1). Following trauma, chemical mediators are released locally from the damaged tissues that can sensitize and, at times, activate the nociceptors of the A-delta and C fibers. Two such agents are the eicosa-noid prostaglandins that are sensitizers derived from injured cells and the peptide bradykinin that is an activator derived from plasma kinino-gens. The activation of nociceptors results in the release from C fiber terminals of the pep-tide substance P that, in turn, causes mast cells to release histamine, which excites nociceptors.
The edema associated with an injury results from the actions of substance P, which pro-duces plasma extravasations, and of calcitonin gene-released peptide that results in the dilation of blood vessels. In addition, the edema causes
Figure 9.1: Spinal cord terminations of dorsal root fibers that mediate pain. The A-delta fibers (pain, temperature, and touch) terminate in laminae I and V, where they synapse with projection neurons (P) whose axons ascend in the pain pathways illustrated in Fig. 9.2. The C fibers (pain and temperature) terminate in lamina II. Interneurons (I) in lamina II have axons that synapse with pro-jection neurons in laminae I and V. (Refer to Table 7.4.)
release of more bradykinin. Other chemical mediators include (1) serotonin (5HT) derived from platelets, (2) potassium ions derived from damaged tissue cells acting as activators of nociceptors, and (3) substance P released from the afferent nerve terminals acting as a sensi-tizer of nociceptors. The effectiveness of aspirin and other anti-inflammatory analgesics in the control of pain occurs because they inhibit an enzyme involved in the synthesis of prosta-glandins. The subjective perception elicited by a brief, intense stimulus is of a sharp, short-duration pain (first pain) followed by a dull, prolonged pain (second pain). First, pain is transmitted by the A-delta fibers that convey information from the thermal and mechanical receptors. Second, pain is transmitted by C fibers activated by polymodal receptors. The viscera contain silent receptors. Usually, these receptors are activated by noxious stimuli.
However, their stimulation (firing threshold) is markedly reduced by inflammation and a vari-ety of chemicals that produce a syndrome called hyperalgesia (excessive response to a minimal stimulus that is often perceived spontaneously).
To distinguish between nociception and pain is basic to an understanding of sensory sys-tems. Nociception implies the reception by nociceptors of stimuli that form signals to pro-vide information to the CNS of tissue damage eliciting a noxious stimulus. Pain is the percep-tion of an unpleasant sensapercep-tion. Perceppercep-tions, such as pain, are abstractions of the sensory input by the CNS. Pain is said to be a subjec-tive perception with a psychological dimen-sion. A noxious stimulus that triggers a nociceptor to respond is not necessarily per-ceived as pain.
Neurologists usually test for cutaneous pain simply by pricking the skin with a sterile, dis-posable, hypodermic needle. Thermal sensibil-ity is evaluated by applying a tube containing ice (40°F) and another containing warm water (110°F) to a body part. Temperature differences of 5–10°F are normally detected subjectively.
The thermal receptors sensing heat and cold are located in free nerve endings. Small shifts in the skin temperature, of about 0.2°F, are
suf-ficient to alter the firing rate of the endings. In essence, thermoreceptors are not objective sen-sors of actual skin temperature; rather, their role is to signal information resulting in adjust-ments to the environment. A perception is espe-cially vigorous when the change is rapid. For example, the perception of hot occurs when a
“cold” hand is placed in lukewarm water. Also, a momentary distorted feeling of coolness is perceived when a foot is placed in a bathtub with hot water.
AFFERENT (FIRST-ORDER) NEURONS Pain and temperature inputs are conveyed via two types of first-order afferent neuron whose cell bodies are in dorsal root ganglia, or the trigeminal ganglion: (1) faster-conducting, lightly myelinated A-delta fibers and (2) slow-conducting, unmyelinated C fibers (see Fig.
9.1); maximum velocities are 30 and 2 m/s, respectively (see Table 7.4). The A-delta affer-ents have low-threshold receptors and conduct signals perceived as sharp localized pain. The C fiber afferents have high threshold receptors and are involved in diffuse persistent pain that might possess aching, burning, or itching qual-ities. Diffuse pain, presumably the result of released chemicals, often is preceded by sharp stabbing pain.
Neurons excited exclusively by nociceptors are called nociceptive-specific neurons. Other first-order neurons involved with the pain path-way conveying input from low-threshold mechanoreceptors are called wide dynamic range neurons. Both the A-delta and C fibers release the excitatory transmitter glutamate and various neuropeptides, especially substance P.
The A-delta afferents, with low-threshold receptors, conduct impulses perceived as sharp, pricking sensations that are accurately local-ized and categorlocal-ized as fast or initial pain.
The C afferents, with high-threshold recep-tors, sense pain as a burning sensation with a slower onset and as a more persistent and less distinctly localized modality known as slow or delayed pain. Both fast pain and slow pain are
Chapter 9 Pain and Temperature 159
essentially somatic sensations from superficial receptors in the body.
In addition, deep or visceral pain, subjec-tively characterized as aches with at times a burning quality, results from stimulation of deep somatic and visceral receptors. This form of pain is associated with inputs conveyed by A-delta and C fibers in both somatic and visceral nerves.
Stimulation of mechanoreceptor nocicep-tors (e.g., from a knife cut or pin prick) and thermal nociceptors in free nerve endings evokes a neural code that is conveyed via A-delta fibers and perceived as sharp and pricking pain (or temperature). Stimulation of thermal and polymodal nociceptors (mechani-cal, heat, and chemical noxious stimuli) in free nerve endings evokes codes that are conveyed by C fibers and perceived as slow, burning pain (or temperature). Thermal nociceptors respond selectively to heat and cold. In humans, heat receptors respond selectively when the temper-ature exceeds the heat pain threshold of 113°F.
Cold receptors respond to noxious cold stimuli.
Pain in Dermatomes
A dermatome is a sensory segment of skin innervated by fibers from one dorsal root (see Fig. 7.3). Dermatomes from successive spinal segments overlap. Hence, the interruption of one complete dorsal root could result in only the diminution (not loss) in sensation in part of the dermatome. However, the irritation of a dorsal root can produce pain in one or more dermatomes. In herpes zoster (shingles), there is an intense and persistent pain in one or more dermatomes. This pain is a consequence of the activation of pain fibers by vericella zoster virus, which primarily affects one or more dorsal root ganglia or the trigeminal ganglion.
Mechanical compression (e.g., following a slipped disk) of a dorsal root can irritate the dorsal root and produce pain over a dermatome.
PATHWAYS FROM THE BODY, LIMBS, AND BACK OF HEAD Pain and temperature pathways from the body, limbs and back of the head, posterior to
the coronal plane through the ears (see Fig. 9.2), are components of the anterolateral pathway (located in the white matter of the anterolateral quadrant of the spinal cord). The tracts are the (1) (lateral) spinothalamic tract, terminating in the thalamus, (2) spinomesencephalic tract, ter-minating in the periaqueductal gray (PAG) of the midbrain, and (3) spinoreticular tract, ter-minating in the brainstem reticular formation.
The anterior spinothalamic tract conveying light touch is included in the anterolateral path-way (see Fig. 10.3). Additional fibers conveying nociception are incorporated in the spinocervi-cothalamic pathway located in the dorsal columns of the lemniscal system (Chap. 10).
The A-delta and C fibers enter the spinal cord as the lateral bundle of the dorsal root.
They bifurcate into branches that ascend and descend one or two spinal levels in the postero-lateral fasciculus (tract of Lissauer; see Fig.
7.6), from where they enter and terminate in the dorsal horn (see Fig. 9.2). The A-delta fibers have excitatory synapses with projection neu-rons. The C fibers synapse with interneurons interacting with (1) projection neurons whose axons ascend to higher centers in the brain and (2) inhibitory interneurons that modulate the flow of nociceptive information to higher cen-ters. The A-delta fibers synapse with neurons in laminae I, II, and V; C fibers synapse with neu-rons in laminae I and II. Branches of each fiber terminate in several spinal levels. According to the gate control theory (see Fig. 9.3), process-ing of these inputs occurs within the dorsal horn by interactions involving nociceptive-spe-cific neurons, wide dynamic range neurons, interneurons, and projection neurons. Descend-ing control mechanisms also are important in pain modulation (see Fig. 9.4).
Cells in several laminae contribute differen-tially to separate components of the spinothal-amic tract. About half of the fibers arise from lamina I, and the rest arise equally from lami-nae IV–V, and VII–VIII. Roughly 90% of the second-order fibers decussate; the remainder ascends ipsilaterally.
The pain and temperature pathways termi-nate in several thalamic nuclei including but
Chapter 9 Pain and Temperature 161
Figure 9.2: The pain and temperature pathways originating in the spinal cord: the lateral spinothalamic tract, spinomesencephalic (spinotectal), and spinoreticulothalamic fibers. Note that the ventral posterolateral (VPL) thalamic nucleus projects to the body regions of both SI and SII of somatosensory cortex and that the intralaminar thalamic nuclei project diffusely and widely to the cerebral cortex. The lamination of the lateral spinothalamic tract is shown on the right side of the cross-sections of the spinal cord (C, cervical; T, thoracic; L, lumbar; S, sacral levels).
not limited to the ventral posterolateral nucleus (VPL), posterior nucleus (PTh), and intralami-nar nuclei (Chap. 23). VPL and the ventral pos-teromedial nucleus (VPM), which receives somatosensory information from the head, are called the ventrobasal complex (VB). In terms of the nature of the nociceptive inputs, there are two significant differences between these thal-amic nuclei: (1) The intralaminar nuclei, acti-vated via the spinoreticulothalamic pathway, receive input from neurons of spinal laminae VI, VII, and VIII conveying information from large complex nociceptive fields; (2) VB and PTh, part of the ventral group of thalamic nuclei, receive input from laminae I and V via
the spinothalamic pathway, which conveys information primarily from nociceptive-spe-cific and wide dynamic range neurons.
The (lateral) spinothalamic tract originates from projection neurons of laminae I, V, VI, and VII. After the axons of its second-order neurons decussate in the anterior white com-missure (anterior to central canal), they ascend in the anterolateral pathway and terminate pri-marily in VPL and PTh thalamic nuclei (see Fig. 9.2). Some collateral branches terminate in the brainstem reticular formation. This tract conveys information perceived with an overlay of the discriminative aspects associated with various subtleties associated with the sensation
Figure 9.3: Gate control model for pain modulation. The model postulates the interaction of (1) the C pain fibers that have inhibitory synapses with an interneuron and excitatory synapses with a projection pain neuron, (2) the myelinated A-alpha and A-beta non-nociceptive fibers that have excitatory synapses with both the interneuron and the projection pain neuron, and (3) the interneu-rons that have inhibitory synapses with the projection pain neuron. See text for further explanation.
of sharp pain and, in addition, with thermal sense (temperature).
At successively higher levels of the spinal cord, new fibers join the tract on its medial
aspect; this produces a laminated somatotopi-cally organized tract; that is, each body seg-ment (or dermatome) is represented in a portion of the tract (see Fig. 7.6). As a
conse-Chapter 9 Pain and Temperature 163
Figure 9.4: Pain control and modulation. Pain can be modulated by the release of opioid pep-tides. Neurons of the periaqueductal gray in the midbrain have excitatory synaptic connections with serotonergic neurons in nucleus raphe magnus and with noradrenergic neurons in the lower brain-stem reticular formation. The serotonergic neurons (1) have inhibitory synapses with nociceptive projection neurons and (2) excitatory synapses with endorphin-containing interneurons (E), which have inhibitory synapses with the nociceptive projection neurons (P). The noradrenergic (norepi-nephrine) neurons also have excitatory synapses with the endorphin-containing interneurons. These activities modulate the excitatory synaptic influences of the glutamate and substance P transmitters of the A-delta fibers with the nociceptive projection neurons.
quence, in the upper spinal cord, pain and tem-perature fibers from the sacral region are located posterolaterally and those from the sacral region are located anteromedially. The VPL thalamic nucleus is also somatotopically organized with the sacral and lumbar (lower body) levels located laterally and the thoracic and cervical levels medially. This tract is also called the lateral pain system or neospinothal-amic tract (meaning new phylogenetically).
Axons of the third-order pain and tempera-ture neurons located in the thalamus ascend through the posterior limb of the internal cap-sule and corona radiata and terminate in the parietal lobe of the cerebral cortex (Chap. 25).
Fibers from VPL terminate in lamina IV of the primary somatosensory cortex (SI; areas 3, 1, and 2 of the postcentral gyrus), whereas fibers from PTh terminate in lamina IV of the sec-ondary somatosensory cortex (SII; areas 3, 1, and 2 near the lateral fissure; Chap. 25). The thalamus might be associated with the percep-tion of pain, whereas the parietal lobe and other cortical areas are involved in the appreciation and the localization of pain and of the integra-tion of stimuli from the pain pathways with the other sensory modalities.
The spinomesencephalic tract is composed of the fibers of projection neurons in laminae I and V that decussate in the anterior white com-missure and ascend in the anterolateral path-way. It terminates in the periaqueductal gray (PAG) of the midbrain (see Fig. 9.4) and is involved in the modulation of pain and in the functioning of the reticular system (Chap. 22).
The spinoreticular tract is integrated into the spinoreticulothalamic pathway terminating in the intralaminar thalamic nuclei (Chap. 21).
The spinoreticular fibers originate from neu-rons in laminae VII and VIII, which receive inputs from large, complex, receptive fields in the periphery. The spinoreticular tract consists of crossed and a few uncrossed fibers that, along with collateral fibers from the spinothal-amic tract, terminate in the multineuronal, mul-tisynaptic complex known as the brainstem reticular formation (Chaps. 13 and 22). Reticu-lothalamic fibers terminate in the intralaminar
nuclei of the thalamus, in the hypothalamus, and in limbic structures. From the spinal cord, there are direct projections to the hypothala-mus. This slowly conducting multisynaptic pathway conveys diffuse poorly localized pain from both somatic and visceral sources. The intralaminar nuclei project to widespread areas of the cerebral cortex, including the frontal lobes. The influences exerted by this pathway are integrated into autonomic and reflex responses to pain and to affective–motivational responses. As a consequence, this pathway is also called the paramedian pain pathway or the paleospinothalamic pathway (old phylogenetic pathway) or medial pain system.
The neospinothalamic pathway, via the VPL nucleus, projects to the primary and secondary somatic sensory areas of the cerebral cortex.
These are essential for spatial and temporal dis-crimination of painful sensations. In contrast, the paleospinothalamic pathway mediates the autonomic and reflexive responses associated with pain and, in addition, the emotional and affective responses.
The roles of the cerebral cortex and the thal-amus in the perception of pain are complex.
Several clinical observations following certain surgical procedures are relevant to an under-standing of the perception of pain. Surgical intervention in various locations, both of the peripheral and central nervous systems, has not proven to be effective in permanently relieving pain. Surgery can abolish the perception of pain temporarily, but it subsequently can return with new manifestations that are unpleasant and frequently different than any pain the patient has experienced previously. These include shooting pain, numbness, cold, burn-ing, and aching sensations. Some procedures in the brain can elicit more distress to the patient than the original pain. Spontaneous lesions can result in marked distortions of pain and pain-related symptoms (see Thalamic Syndrome, Chap. 23). The bizarre sensations perceived by an amputee in a phantom limb are expressions of processing within neural centers deprived of normal stimulation (see later). Destructive sur-gical lesions of the intralaminar and posterior
thalamic nuclei can alleviate intractable pain;
in time, the pain might return.
Several surgical interventions suggest some functional roles for various regions of the brain:
(1) Nociceptive information from one half of the body is conveyed to the same side of the spinal cord and then crosses over to the con-tralateral side to ascend as the neospinothala-mic pathway to where aspects of perception occur in the thalamus and the somatosensory areas of the cortex. Painful stimuli can be per-ceived on the contralateral side of the body fol-lowing ablation of the somatosensory cortex of a hemisphere. This is accomplished when the entire thalamus and other subcortical structures are intact. (2) The cortex of the frontal lobe and cingulate gyrus are involved in some way with the psychological responses to pain (Chap. 25), as are the dorsomedial and anterior thalamic nuclei with connections to the cortex of the frontal lobe (Chap. 22). Lesions of these nuclei, or of the nerve fibers linking them to the frontal lobe (called prefrontal leukotomy), lowers the agony associated with the persistent pain by altering the psychological response to the painful stimuli. The downside to this approach is the negative changes in the personality and intellectual status of the patient (Chap. 25).
Bilateral severing of the fibers linking the cin-gulate gyrus to the frontal lobe (cingulotomy) can relieve the response to pain without the concomitant personality changes.
MAJOR CLASSES OF FUNCTIONALLY DEFINED NEURONS AND THE
SPINOTHALAMIC TRACTS Major Classes of Neurons in the Spinal Cord Associated with “Pain”, and Ascending Projections
Lamina I contains three major classes of lat-eral spinothalamic tract neurons (Figs. 9.1 and 9.4). Nociceptive-specific neurons (NS) with small cutaneous receptive fields respond to noxious mechanical and/or thermal stimuli, but not to innocuous stimulation. In addition, they respond to noxious stimulation of muscles,
joints, and viscera, Polymodal nociceptive neu-rons (PC), dominated by C fiber input, respond to noxious heat, cold, or pinch and also might respond to stimulation of muscles, joints, or viscera. Thermoreceptive-specific neurons (COLD) respond to innocuous cooling.
Laminae IV and V contain two major types of anterior spinothalamic tract cell. Low-threshold cells (LT) respond only to innocuous mechanical stimulation such as brushing (hair) or to both brushing and graded pressure. Wide dynamic range nociceptive neurons (WDR) respond to innocuous and noxious stimuli over fairly large cutaneous fields in a graded manner.
Functional Considerations
Studies of the anatomy of the pain system indicate that painful stimuli activate multiple pathways and, therefore, multiple nuclei, gan-glia, and cortical areas of the forebrain, The processing nuclei assimilate past experiences and present context that collectively produce and result in the total multidimensional pain experience. These pathways and centers can contribute different aspects of pain sensation.
The conscious pain–emotion content is con-structed by the integration of contributions of the constellation of neural activity within the processing centers of the pain pathways.
Recent functional positron-emitting tomog-raphy (PET) and magnetic resonance imaging (MRI) investigations of the cerebrum have shown cortical areas that are activated by nox-ious heat and noxnox-ious cold stimuli, including the primary and secondary somatosensory cor-tices, lateral operculum (Chap. 25), insula and anterior cingulate gyrus ((see Fig. 1.5).
Accompanying the perception of pain, PET activation has been observed in the periaque-ductal gray, hypothalamus, amygdala, cerebel-lum, and some nuclei of the basal ganglia, structures that all receive some ascending noci-ceptive input.
Salient Features of the Spinothalamic and Trigeminothalamic Pain Pathways
The lateral spinothalamic tract pain and tem-perature system (LSTT; see Fig. 9.2) arises
Chapter 9 Pain and Temperature 165
from neurons called cold cells, polymodal nociceptive cells, and nociceptive-specific cells located in lamina I of the spinal cord that decussate and form the ascending LSTT. Dur-ing its ascent into the thalamus, the tract emits collateral branches that terminate in parts of the brainstem reticular formation (Chap. 22) and the periaqueductal gray. Within the thalamus, fibers are distributed to several nuclei and their subdivisions, including the ventral caudal por-tion of the dorsomedial nucleus (DM), the ven-tral posterolateral nucleus (VPL), venven-tral posterior inferior nucleus (VPI), the central lat-eral and parafascicular intralaminar nuclei, and the posterior portion of the ventral medial nucleus (VMpo), part of the posterior thalamic group (see Fig. 9.5). In turn, DM projects to the base of the anterior cingulate gyrus; when acti-vated, the sensation of burning pain can be felt.
The densest LSTT terminations are in VMpo, which projects to the dorsal margin of the insula within the lateral fissure and is involved in “sensory representation of the physiological condition of the body” (lesions of this area have a minimal effect on the pain sensation) and in VPI, which also projects to the insula (activated by noxious heat or cold stimuli).
Trigeminothalamic pain pathways are basically similar to the spinothalamic pain pathways except that fibers to the ventrobasal complex ter-minate in VPM rather than VPL (see Fig. 9.6).
The anterior spinothalamic tract crude touch and movement sensation system (ASTT) projects from neurons called wide dynamic range and low-threshold neurons in lamina 5) whose axons decussate and form the ascending ASTT (see Figs. 10.3 and 10.4). As the tract ascends, its collateral branches terminate in some brainstem reticular formation nuclei before terminating in the central lateral (CL) nucleus of the intralaminar nuclear group, VPL, and VPI. VPL projects somatotopically mainly to the primary somatosensory cortex (areas 3 and 1) and VPI projects mainly to sec-ondary somatosensory cortex in the insula (Chap.25). The trigeminothalamic tracts have equivalent connections, which within the ven-trobasal complex involve VPM. The functional
roles of the pain pathways are subtlety influ-enced by the tracts and nuclei of the reticular system (ascending reticular activating system [ARAS], Chap 22). These include (1) the spin-oreticular and spinomesencephalic tracts from the spinal cord (see Fig. 9.2) reticuloreticular and reticulothalamic tracts from the reticular formation of the brainstem, and the thalamo-cortical projections to the cerebral cortex and (2) nuclei such as the reticular nuclei of the brainstem and the CL and other intralaminar thalamic nuclei.
An insight into the intricacies of pain is provided by Craig and Dostrovsky (1999), who wrote “The most parsimonious and prospective view is that the activity of all of these ascend-ing pathways must be integrated in the fore-brain in the context of current conditions and past experience in order for all aspects of the sensation of pain to be generated.” Elimination of a portion of the system or a given pathway, such as by a partial lesion in the periphery, in the spinal cord or in the forebrain, could cause an imbalance that could have variable effects on integrated sensation or in the central pain syndrome (see later). For example, it may result in pain without a noxious stimulus as in the phantom limb and central pain syndromes.
These conditions emphasize the complexity of the spinal and supraspinal connections still to be identified that are involved in the experience of pain.
WALL’S CONCEPT OF PAIN IN TARGET MOTOR RESPONSES
“Pain for me arrives as a complete package,”
at the same time painful and miserable” (Wall and Melzack, 1999). Pain is also thought of as a subjective phenomenon perceived both as a sensation (cognitive) and as an affective (e.g., fear, miserableness) feeling tone. Thus patients suffering from intense pain and given morphine describe affect perceptions in the absence of cognitive pain. Other definitions are that pain is an abstraction of nociception or that pain is not a sensation, but a perception. Pain has been