Centrally the butterfly-shaped grey matter of the cord is divided in the midline by the central canal. The grey matter passing dorsally to the central canal is referred to as the posterior grey commissure and the grey matter passing ventrally to the central canal is referred to as the anterior grey commissure. Arising from the area of the ventral lateral sulci are the ventral roots of the spinal cord, which just as they exit the vertebral foramina combine with the afferent axons of the dorsal root ganglion neurons as they enter the vertebral foramina to form the root of the spinal nerve. Entering the spinal cord at the dorsal lateral sulcus are the sensory dorsal roots, completing their journey to the cord from the dorsal root ganglion cells (Fig. 7.5). The areas of grey matter that give rise to or receive the afferent and efferent input resemble the shape of a horn and are thus termed the anterior and posterior horns. The anterior horn does not extend through the anterior funiculus and reach the surface of the cord. The posterior horn projects much more deeply into the dorsal funiculus and except for a small band of translucent neurons, the substantia gelatinosa, it would extend to the posterior surface of the cord. A small angular projection from the intermediate areas of the cord forms the lateral horn of grey matter that only occurs between the levels of the first thoracic to the second lumbar segment. This lateral outgrowth of grey matter houses many of the presynaptic neurons of the sympathetic nervous system.

Figure 7.5 The various structures and nerve fibre pathways in a cross-sectional view of the spinal cord.

The neurons of the grey matter form a complex intermingled array involving multiple synaptic connections with many of the axons crossing the midline via the anterior and posterior commissures. Some of the neurons are intrasegmental and their axons and dendrites remain within the same segment of the spinal cord as the neuron soma. Other neurons are intersegmental and their axons and dendrites spread over many segments both rostrally and caudally. In many parts of the neuraxis groups of neurons, usually with a related functional activity, cluster together into nuclei or, when large enough, ganglia. Several nuclei have been identified in the grey matter of the spinal cord. The most predominant neurons in the ventral grey areas are the large multipolar neurons whose axons emerge from the spinal cord to form the anterior horn, and contribute to the spinal nerves, to ultimately innervate the skeletal muscles of the body. These neurons are also referred to as alpha-efferents or alpha motor neurons. Also present in large numbers in the anterior horn are slightly smaller neurons whose axons supply the intrafusal fibres of the muscle spindle called gamma-efferents or gamma motor neurons (Fig. 7.6).

Figure 7.6 The various locations of grey matter nuclei of the spinal cord.

The neuron groupings in the posterior horns involve four main nuclei, two of which extend through the length of the cord and two that are present only at selective levels of the cord. The substantia gelatinosa of Rolando extends throughout the cord and composes the extreme tip of the dorsal horn. These neurons are involved with signal processing of afferent information from the dorsal root ganglion neurons and are thought to play an essential role in the initial processing of pain due to extensive connections with incoming axons destined to form the spinothalamic tracts (Fig. 7.6).

A second nuclear group that extends throughout the spinal cord is located ventral to the substantia gelatinosa and is referred to as the dorsal funicular group or the nucleus proprius (Fig. 7.6). Lying ventral to the nucleus proprius in the basal region of the dorsal horn and extending from the eighth cervical region of the cord to the fourth lumbar region of the cord is the nucleus dorsalis or Clark’s nucleus (Fig. 7.6). Finally, a small group of nuclei known as the visceral grey area, or nucleus centrobasalis, is present only in the lower cervical and lumbosacral segments of the cord.

The intermediate region of the grey matter is composed of relatively small neurons that function as the presynaptic sympathetic neurons of the autonomic nervous system. Two regions are usually identified, the intermediolateral group (IML), which houses the presynaptic sympathetic neurons and the intermediomedial group (IMM), where similar small neurons to the IML reside and probably act as multimodal integrators for the output IML neurons. Neurons from both the IML and IMM send axons via the white rami communicants to the paravertebral ganglia that extend from T1 to L2 vertebral levels.

Rexed’s laminae can be used to classify functional aspects of grey matter

In the 1950s and early 1960s an architectural scheme was developed to classify the structure of the spinal cord, based on the cytological features of the neurons in different regions of the grey substance. It consists of nine laminae (I–IX) that extend throughout the cord, roughly paralleling the dorsal and ventral columns of the grey substance, and a tenth region (lamina X) that surrounds the central canal (Rexed 1964) (Fig. 7.8).

Figure 7.8 The laminar divisions of the spinal grey matter as per Rexed.

Quick facts 7.4

Alar and basal plate development

Figure 7.7 During embryonic development the alar or roof plate of the spinal cord develops into the neurons that receive afferent information from the dorsal root ganglion cells. The basal or floor plate develops into the motor output neurons of the spinal cord.

A brief description of the functional characteristics of these laminae follows.

Laminae I–IV

These areas are considered the main receiving junctions for primary afferent information. This region is characterised by complex multisynaptic networks of both intra- and intersegmental neurons. Many of the pathways cross the midline of the cord and ascend or descend in contralateral tracts (Fig. 7.9).

Figure 7.9 Another view of the grey matter laminae which illustrates the groupings of neurons forming small nuclear units.

Laminae V and VI

Quick facts 7.5

Various rexed laminae can be referred to by more than one name

Laminae	Names
I	Lamina marginalis
	Layer of Waldeyer
II and III	Substantia gelatinosa
III and IV	Nucleus proprius
V	Deiter’s nucleus
VII	Clark’s column
	Thoracic nucleus
X	Substantia gelatinosa centralis

These areas receive proprioceptive primary afferent information as well as descending collateral input from axons of the corticospinal and reticulospinal tracts. This area is probably very involved in multimodal integration and regulation of movement (Fig. 7.9).

Lamina VII

The lateral aspect of this area receives extensive efferent and afferent connections from the cerebellum, spinocerebellar, spinotectal, spinoreticular, and rubrospinal tracts and is involved in the multimodal integration of posture and movement.

The medial aspect of this area contains numerous complex networks of connections between propriospinal neurons. This area is probably involved in the integration of the complex propriospinal reflex network of the spinal cord concerned with both movement and autonomic function (Fig. 7.9).

Lamina VIII

This area receives collateral projections from adjacent laminae, medial longitudinal fasciculus, and vestibulospinal and reticulospinal tracts and profuse projections from the contralateral lamina VIII region. Output of this area influences both ipsilateral and contralateral neuron pools through both direct projections to the alpha motor neurons and projections to the gamma motor neuron pools (Fig. 7.9).

Lamina IX

This area is populated with both alpha and gamma motor neurons as well as interneurons.

Lamina X

This area comprises the grey matter in close approximation to and surrounding the central canal. This area also consists of the dorsal and ventral commissures and the central gelatinous substance.

The spinal cord itself consists of columns of cells and axon fibre tracts that allow communication throughout the length of the spinal cord and with supraspinal levels of the neuraxis. It is convenient to describe the axon fibre tracts of the spinal cord with respect to the funiculus in which they are located.

Axon fibre tracts of the dorsal funiculus

The dorsal columns are composed of the medially located fasciculus gracilis and the more laterally located fasciculus cuneatus (Figs 7.10, 7.11, 7.12). These pathways transport information from receptors in the periphery about fine and discriminative touch, conscious proprioception, pressure, two-point discrimination, and vibration sense. The primary afferent axons enter the spinal cord grey matter through the dorsal horn and synapse on the neurons in laminae V and VI. The secondary afferents ascend in the ipsilateral dorsal columns. Information from the lower limb and trunk is carried in the gracile funiculus and information from the upper limb and hand by the cuneate funiculus and synapse ipsilaterally in the gracile and cuneate nuclei of the caudal medulla.

Figure 7.10 The projections of the dorsal columns to the neurons in the cuneate and gracile nuclei in the caudal medulla region of the neuraxis.

Figure 7.11 The fibre tracts in a cross-sectional view of the spinal cord.

Figure 7.12 The pathway of the dorsal column/medial lemniscal system through the various levels of the neuraxis.

Neurons then decussate in the caudal medulla as the internal arcuate fibres and ascend to the contralateral thalamus via the medial lemniscus of the brainstem. Some fibres contained in the cuneate fasciculus arising from proprioceptive afferents project to the cerebellum. These projection fibres form the external arcuate fibres and form the cuneocerebellar tract.

Axon fibre tracts of the lateral funiculus

The anterolateral system contains the fibre tracts of the spinothalamic tract and some of the fibres comprising the spinoreticular and spinomesencephalic tracts. These last two pathways provide the afferent limb for neuroendocrine and limbic responses to nociception (Figs 7.11 and 7.13).

Figure 7.13 The pathway of the anterior and lateral spinal thalamic tracts (anterolateral system) through the various levels of the neuraxis.

The spinothalamic pathway, from a clinical standpoint, carries pain and temperature sensation from the entire body, excluding trigeminal distributions, to the thalamus. Primary afferent fibres have cell bodies located in the dorsal root ganglion (DRG) and their central processes synapse in the dorsal horn laminae I, II, and V, predominately. Secondary afferents, which form the spinothalamic tract proper, decussate (cross the spinal cord) about 2–3 levels higher in the spinal cord and ascend in the anterolateral funiculus to the ventral posterior lateral (VPL) nucleus of the thalamus. Sensory modulation can occur in the brain, thalamus, or spinal cord, especially in lamina II, and is also influenced by visceral afferents in lamina V where convergence of afferent information can result in referred pain phenomena.

The spinocerebellar pathways include the ipsilateral dorsal and the contralateral ventral pathways. These pathways convey unconscious proprioception mainly from the joint receptors and muscle spindle fibres of the muscles and joints of the body and integrated data from multimodal neuron systems in the spinal grey matter to the cerebellum.

The ventral spinocerebellar pathway conveys information about the ongoing status of interneuronal pools in the spinal cord to the cerebellum. It therefore provides continuous monitoring of ascending and descending information concerning locomotion and posture. The neurons of this tract originate in laminae V–VII between L2 and S3. Their projection axons decussate to the other side so that they ascend in the contralateral anterolateral funiculus. These fibres then decussate again via the superior cerebellar peduncle to synapse on neurons in the anterior part of the ipsilateral cerebellum (see Fig. 7.11).

The dorsal spinocerebellar tract neurons originate medially to the IML column of the spinal cord between C8 and L2/3.

The primary afferent cell bodies are located in the DRG and their central processes synapse with the above-mentioned neurons near the entry level or after ascending for a short distance in the dorsal columns. Secondary afferents ascend in the ipsilateral dorsolateral funiculus, lateral to the corticospinal tracts, and enter the ipsilateral cerebellum via the inferior cerebellar peduncle. Via this pathway, the cerebellum is provided with ongoing information about joint and muscle activity in the trunk and limbs. The cuneocerebellar pathway carries the same type of information from the upper limb and cervical spine via the cuneate fasciculus of the dorsal columns (see Fig. 7.11).

The anterior and lateral corticospinal tracts are important spinal tracts in the control of volitional movement. The fibre tracts are composed of axons from many different areas of the cortex as well as about 50% of their axons from unidentified areas. These tracts contain about 50% of their axon projections from the large pyramidal neurons of the primary motor cortex and association motor cortex. The lateral corticospinal tract descends in the spinal cord anterolateral to the posterior horn of grey matter and medial to the posterior spinocerebellar tract (Figs 7.11 and 7.14). It contains a large number of motor axon projections from cortical areas 1–4 and 6 to the hands, arms, legs, and feet. Its defining role is to convey motor signals to the ventral horn cells (VHCs) at the lower aspect of the cervical and lumbosacral enlargements of the spinal cord, thus controlling distal limb movements and coordinating distal and proximal muscles to achieve specific trajectories in space. Each corticomotoneuronal cell can achieve these complex goals by synapsing on interneuronal cells that communicate with whole groups of VHCs.

Figure 7.14 The pathway of the anterior (ventral) and lateral corti-cospinal tracts through the various levels of the neuraxis.

Axons from the projection neurons in the cortex descend in the internal capsule of the cerebrum through the cerebral peduncle of the mesencephalon and continue through the ventral areas of the pons until they enter the pyramids of the medulla oblongata. As the fibres descend in the medulla, about 68% of the fibres cross to form the lateral corticospinal tracts in the lateral funiculus of the contralateral side of the spinal cord; about 30% of the fibres do not cross and form the anterior corticospinal tracts in the ventral funiculus of the ipsilateral side of the spinal cord. The remaining fibres continue as uncrossed fibres of the lateral corticospinal tracts (Fulton & Sheenan 1935).

The anterior corticospinal tract runs adjacent to the anterior median fissure and descends to about the middle of the thoracic region. It contains most of the uncrossed motor projection fibres from the cortex and is thought to modulate axial musculature involved in strut stabilisation and postural control.

Traditionally, the anterior and lateral corticospinal tracts were referred to as the pyramidal tracts. These tracts have the distinction among motor pathways of forming a continuous non-interrupted pathway from the cortex to the grey matter of the spinal cord. A number of other tracts also involved in motor control, including the rubrospinal, vestibulospinal, and other tracts that form intermediate synaptic connections in the brainstem, are referred to as the extrapyramidal tracts.

Most of the axons of both the anterior and lateral corticospinal tracts synapse on interneurons located in laminae IV to VII of the grey matter of the spinal cord (Nyberg-Hansen 1969). Most physiological evidence suggests that the majority of the corticospinal fibres of both tracts act to facilitate flexor groups of muscles and inhibit extensor groups of muscles, which is the opposite effect observed by projections of the vestibulospinal tracts. Injuries involving the corticospinal tracts affect the motor control of the peripheral muscles differently at different levels of the neuraxis. Injuries above the medulla decussation affect the contralateral peripheral muscles. Injuries below the decussation affect the peripheral muscles ipsilateral to the lesion. It must be remembered that not all of the corticospinal fibres cross the midline so that a lesion to a motor cortical area on one side of the corticospinal tract above the decussation will affect the motor control on both sides of the body to a certain extent. This contributes to the understanding of the ipsilateral pyramidal paresis observed when a decreased cortical function (hemisphericity) occurs.

Vestibulospinal tract

The vestibulospinal tracts, lateral and medial, descend in the ventral funiculus, and mediate reflexes (vestibulospinal) that enable an individual to maintain balance and posture despite the effect of gravity and changes in the centre of mass due to movement of the trunk, head, and limbs. The lateral segments, the lateral vestibulospinal tract, descend from the lateral vestibular nucleus uncrossed and exert modulatory effects on the ipsilateral anterior column neurons in the grey matter through the length of the cord. The medial segments of this pathway, the medial vestibulospinal tracts, arise from the medial and inferior vestibular nuclei and descend first in the medial longitudinal fasciculus before entering the vestibulospinal tracts of the cord. This pathway is both crossed and uncrossed and only projects to the cervical and thoracic levels of the cord and as such is probably only involved with upper limb and neck movements (Figs 7.11 and 7.15).

Figure 7.15 The pathway of the vestibulospinal tracts through the various levels of the neuraxis.

The vestibulospinal tracts transport afferent information from the vestibular apparatus of the inner ear and descending efferent information from the inferior and lateral vestibular nuclei. The pathway descends in the ipsilateral ventral funiculus of the spinal cord, dorsal to the tectospinal tract and immediately adjacent to the anterior median fissure. The axon projections of both pathways synapse predominately on alpha and gamma VHCs of laminae VII and VIII. The physiological evidence to date suggests that this pathway has a facilitory effect on extensor muscles and an inhibitory effect on flexor groups.

Tectospinal tract

The fibres of this tract originate from the deep layers of the contralateral superior colliculus in the dorsal midbrain (mesencephalon). The tectospinal tract crosses in the dorsal tegmental decussation of the midbrain, which is ventral to the oculomotor nucleus and the medial longitudinal fasciculus (MLF). It maintains a close relationship with the MLF until it reaches the level of the internal arcuate fibres at the decussation of the medial lemniscus. At this point it passes laterally so that it comes to lie in the ventral lateral white matter of the spinal cord. It then descends in the contralateral medial ventral funiculus of the spinal cord, synapsing on interneurons in laminae VI to VIII that communicate with the alpha and gamma motor neurons of the cervical spine (Szentagothai 1948) (Fig. 7.16).

Figure 7.16 The pathways of the mesencephalic, ponto, and medullary reticulospinal tracts (green) and the tectospinal tract (blue) through the various levels of the neuraxis.

The superior colliculus is a remnant of the optic lobe in primitive animals and is involved in visual reflexes in addition to integration of somatic (especially neck and head), auditory, and visual afferents for spatial orientation of incoming stimuli and associated reflex head and eye movements. It facilitates accurate head and eye movements in response to sound and light stimuli.

Rubrospinal tract

The rubrospinal pathway has been rumoured to be vestigial in humans because of the evolutionary advancement of the corticospinal pathways; however, its presence in primates probably indicates it will eventually be found in humans as well and an open mind needs to prevail. It originates mainly from the large (magnocellular) neurons of the red nucleus in the rostral mesencephalon, decussates slightly more caudally, and descends just ventrally to the corticospinal fibres in the dorsolateral funiculus of the spinal cord contralaterally (Fig. 7.17).

Figure 7.17 The pathway of the rubrospinal tract through the various levels of the neuraxis.

Neurons of the red nucleus share extensive interaction with the cerebellum and basal ganglia and partly mediate their control over spinal motor output. The red nucleus is composed of a magnocellular or large cell and parvicellular or small cell components. Magnocellular components are homologous to the large diameter neurons of the primary motor cortex, while the parvicellular components are homologous to the premotor and supplementary motor areas of the cerebral cortex. The latter component acts as a relay and modulatory centre for feedforward connections between the cerebellum and the cortex.

The rubrospinal tract acts much like the corticospinal tracts in that it affects enhancement flexor tone and inhibition of extensor tone, especially in the proximal limb muscles.

Quick facts 7.7

The history of motor function of the spinal nerve

The anterior spinal nerve roots contain only motor fibres and posterior roots only sensory fibres.

• Charles Bell’s work of 1811 contains the first reference to experimental work on the motor functions of the ventral spinal nerve without, however, establishing the sensory functions of the dorsal roots. In 1822 François Magendie definitively discovered that the anterior root is motor and that the dorsal root is sensory.

• Magendie announced that ‘section of the dorsal root abolishes sensation, section of ventral roots abolishes motor activity, and section of both roots abolishes both sensation and motor activity’.

• This discovery has been called ‘the most momentous single discovery in physiology after Harvey’. In the same volume of Journal de physiologie expérimentale et de pathologie, Magendie gave experimental proof of the Bell–Magendie Law.

• Magendie proved Bell’s Law by severing the anterior and posterior roots of spinal nerves in a litter of puppies. Stimulation of the posterior roots caused pain. Magendie sums it up: ‘Charles Bell had had, before me, but unknown to me, the idea of separately cutting the spinal roots; he likewise discovered that the anterior influences muscular contractility more than the posterior does. This is a question of priority in which I have, from the beginning, honored him. Now, as for having established that these roots have distinct properties, distinct functions, that the anterior ones control movement, and the posterior ones sensation, this discovery belongs to me’ (F. Magendie (1847) Comptes rendus hebdomadaires des séances de l’Académie des sciences, 24: 3).

Autonomic modulatory projection fibres from supraspinal centres to the preganglionic neurons of the autonomic nervous system are known to exist but have been very difficult to isolate as a solid tract of fibres, probably because they are composed of polysynaptic columns of neurons and interneurons that range throughout wide areas of the white matter. The best indications are that most of these projections are located in the lateral fasciculus, with a smaller number also located in the anterior funiculus. Some findings suggest that some of the pyramidal neurons in the frontal cortex that form the corticospinal tracts are actually autonomic modulatory neurons. Other projections are undoubtedly from various hypothalamic and reticular nuclei.

Local spinal cord reflex circuits are also important in volitional movement in that descending motor pathways converge on interneurons to allow complex movement patterns to occur – i.e. corticomotoneuronal cells of the brain alter the trajectory of a limb in space by activating these reflex circuits involving agonist, antagonist, synergist, and neighbouring joint muscle groups. Feedback and feedforward mechanisms are employed by the cerebellum to assist plastic changes in the brain and spinal cord. Some stereotypical reflexes mediated by the spinal cord are state- or phase-dependent. For example, activation of Golgi tendon organs (GTOs) in the soleus and gastrocnemius muscles will trigger a different set of interneurons in the spinal cord, depending on whether the individual is in a state of locomotion or is non-ambulatory, and whether the individual is in the swing or stance phase of gait (Fig. 7.18).

Figure 7.18 (A) The simple muscle spindle (tendon) reflex. The reflex hammer strikes the tendon and causes a stretch of the muscle spindle fibres. This fires the afferent nerve pathway, which then synapses on the ventral horn cell, causing a depolarisation of the ventral horn neuron, which in turn produces a contraction of the extrafugal muscles innervated by the ventral horn neurons. (B) The complex array of modulating inputs that the ventral horn neuron is exposed to at any given moment. Thus even the simple reflex arc that we are all familiar with is much more complex than first imagined.

This is analogous to the stumbling-correction reflex observed in cats. Sensory stimuli to the dorsum of the foot will activate a different set of interneurons, depending on whether the individual is in the stance or swing phase of gait. For example, during stance, the reflex would result in lower limb extension on that side, while during swing, the reflex would result in powerful flexion withdrawal response.

Flexor reflex afferent (FRA) responses result in a whole limb response of flexion and withdrawal. These FRA responses are stereotypical responses serving a protective function. An example includes the response to plantar stimulation of the foot, which results in the withdrawal of the entire lower limb.

When faced with motor or sensory signs and symptoms, it is important to consider the level of decussation in different pathways to assist in identifying the location of a lesion in the various planes of the neuraxis.

A unilateral spinal cord lesion may affect motor control, joint position sense, and discriminatory sensation ipsilaterally, while pain and temperature sensation may be affected contralaterally.

Laminar organisation in the spinal cord is not as complete or as accurate as previously thought. The traditional understanding of the laminar distribution of pathways in the white matter of the spinal cord was that the projections to and from the most distal areas of the body were more lateral in the spinal cord except in the dorsal columns where the reverse occurs. Some variability of these laminar patterns has been demonstrated; however, the general pattern in dorsal column, spinothalamic, and corticospinal tracts is important to understand from a clinical perspective.

Quick facts 7.8

Summary of afferent tracts

The dorsal root neuron receptors that detect pain and temperature synapse on neurons in the substantia gelatinosa area of the grey matter. These neurons then cross the midline of the spinal cord to ascend in the contralateral spinothalamic tracts to the contralateral thalamus. In comparison, the dorsal root ganglion receptors that detect position and proprioception project ipsilaterally to the appropriate nucleus (gracilis/cuneatus) in the caudal medulla. The projections from the nuclear neurons then cross the midline and ascend in the contralateral medial lemniscal tracts to the contralateral thalamus. All of the neurons in the thalamus then project to the appropriate area of the somatosensory cortex. The representation of the somatotopic map of the body in the cortex is referred to as the sensory homunculus. Note the neurons in the trigeminal ganglia are the embryological homologues of the dorsal root ganglion neurons of the spinal cord.

Figure 7.19 Summary of afferent tracts.

There are 31 pairs of spinal nerves divided into cervical (8), thoracic (12), lumbar (5), sacral (5), and coccygeal (1) levels. The spinal nerves are composed of afferent ascending fibres from the dorsal root ganglion neurons and efferent descending fibres from the anterior and lateral horn neurons. These fibres are separated into sensory and motor fibres as the dorsal (sensory) and ventral (motor) roots of the spinal cord.

Quick facts 7.9

Summary of efferent tracts

The pyramidal cells of the cortex form the output neurons of the motor cortex. The pyramidal axons that supply the muscles and effector organs of the face form the corticobulbar tracts and are referred to as the upper motor neurons of the cranial nerves. These projections are crossed for the most part but some ipsilateral projections are also present. The pyramidal axons that supply the muscles and effector organs of the rest of the body are referred to as the corticospinal tracts. The majority of the corticospinal projections or tracts cross the midline to synapse on effector neurons on the contralateral side to their origin, but as in the corticobulbar projections some ipsilateral projections are also present.

Figure 7.20 Summary of efferent tracts.

The spinal nerves represent the neural division of the embryological somite and contain motor, sensory, and autonomic components. The spinal nerves separate into dorsal and ventral rami as they exit the vertebral foramina (Fig. 7.21). The somatic component of the spinal nerve contains the motor nerves to skeletal muscle and the afferent information from a variety of receptors. The visceral component contains the afferent and efferent fibres of the autonomic nervous system.

Figure 7.21 A three-dimensional view of the spinal cord, spinal nerve roots, and paraspinal ganglia. Note the dural layers covering the spinal cord and spinal root pathways.

The dorsal and ventral rami of the spinal nerves than continue to separate into smaller and smaller peripheral nerves, all of which contain both afferent and efferent fibres of the somatic and visceral components. The anatomy of the visceral or autonomic division is discussed in Chapter 8. The functional distribution of the muscular and sensory divisions, including dermatomes and motor actions of peripheral nerves, has been discussed in Chapter 4.

Peripheral nerve fibre classification

The peripheral nerves are made up of nerve fibres of different diameters. Several schemes have attempted classifications of peripheral nerve fibres based on various parameters such as conduction velocity, function, fibre diameter, and other attributes. The two main classification systems in use are the Erlanger and Gasser system and the Lloyd system. Both schemes have two basic categories which divide the fibres into myelinated and unmyelinated groups. Over time and through convention, a combination of the two classification systems has evolved: Erlanger and Gasser is used for efferent fibre classification and Lloyd for afferent fibre classification.

Quick facts 7.10

Peripheral nerves

Figure 7.22 Peripheral nerves. Peripheral nerves can be classified as cranial or spinal nerves. Each peripheral nerve consists of efferent and/or afferent fibres or both. They may be myelinated or non-myelinated, and have a series of connective tissue blankets called endoneurium, perineurium, and epineurium.

Erlanger and Gasser (1937) divided peripheral nerve fibres based on velocity of conduction. These are the three peaks seen on a compound nerve conduction velocity study and can be classified as follows.

A fibres, which are myelinated and have large diameters (22 μm), transport action potentials at the rate range of 120 to 60 m/s. These are further divided into efferent and afferent type A fibres. Efferent type A fibres include:

Aα—to extrafusal muscle fibres;

Aβ—collaterals of Aα; and

Aγ—to intrafusal muscle fibres.

Afferent type A fibres include:

Aα—cutaneous, joint, muscle spindle, and large alimentary enteroreceptors;

Aβ—Merkel discs, pacinian corpuscles, Meissner corpuscles, Ruffini endings; and

Aγ—thermoreceptors and nociceptors in dental pulp, skin, and connective tissue.

B fibres, which are myelinated and have diameters slightly smaller than that of the A fibres, transport action potentials at the rate of 30–4 m/s. Efferent type B fibres compose the fibres of preganglionic autonomic neurons.

C fibres, which are unmyelinated and of small diameter (1.5 μm), transport action potentials at the rate of 4–0.5 m/s. Efferent type C fibres are non-myelinated and compose the fibres of postganglionic autonomic neurons. Afferent C fibres are non-myelinated and convey information from thermoreceptors and nociceptors.

Lloyd’s classification is based on fibre diameters ranging from 22 to 1.5 μm for myelinated fibres and 2–0.1 μm for non-myelinated fibres. Only afferent fibres were classified, and these were arranged into four groups. Myelinated fibres are divided into group I, II, and III, and non-myelinated fibres compose group IV (Table 7.1). Group or type I fibres, which have diameters ranging from 12 to 22 μm, are further divided into groups Ia and Ib. Group Ia fibres are larger, are heavily myelinated, and transmit information from muscle spindles and joint mechanoreceptors. Group Ib fibres are smaller, are moderately myelinated, and transfer information from Golgi tendon organs, and some joint mechanoreceptors.

Table 7.1 Lloyd’s classification of nerve fibres

Quick facts 7.11

Conduction speeds of axons

• Conduction speed depends largely on two factors:

• 1 Axon diameter and

• 2 Myelination.

• Large-diameter fibres conduct faster than small diameter fibres (A, B, C fibres).

• Myelinated fibres conduct faster than unmyelinated fibres.

• Small unmyelinated C fibres conduct at 0.25 m/s.

• Large myelinated fibres conduct at 100 m/s.

Group or type II fibres have a diameter ranging from 6 to 12 μm, are moderately myelinated, and transmit information from secondary sensory fibres in muscle spindles. Group or type III fibres have a diameter ranging from 1 to 6 μm and are composed of unmyelinated nerve fibres ending in connective tissue sheaths which transmit information concerning pressure and pain.

The largest diameter fibres have a number of clinically important, unique properties, which include the following:

1. They have the greatest nerve conduction velocity.

2. They are the most sensitive to hypoxia.

3. They are the most sensitive to compression.

4. They are the most sensitive to thermal changes.

5. They are the most sensitive to bacteraemia and viral toxaemia.

6. They have the lowest threshold to electrical stimuli.

The nociceptive C fibres are the most sensitive to chemicals such as anaesthetic agents.

Quick facts 7.12

Brown–sequard syndrome

Damage to the lateral half of the spinal cord results in motor and sensory disturbances below the level of the lesion. Neural impairment involves:

• Ipsilateral motor paralysis;

• Ipsilateral loss of joint proprioception;

• Ipsilateral loss of vibration sense;

• Ipsilateral loss of two-point discrimination;

• Contralateral loss of pain sensation; and

• Contralateral loss of temperature sensation.

Quick facts 7.13

Brown–sequard syndrome: causes

• Syringomyelia

• Cord tumor

• Haematomyelia

• Trauma (knife/bullet)

• Radiation myelopathy

In contrast to people who fail to feel pain at the time of injury are people that develop pain without apparent injury. Examples of conditions commonly seen in practice include tension headaches, migraines, fibromyalgia, trigeminal neuralgia, and back pain.

The mechanism of pain without cause is thought to occur through central pain mechanisms. In central pain, an arm or a leg that apparently has nothing wrong with it can hurt so much or feel so strange that patients struggle to describe the pain or the feelings that they perceive (Boivie 2005). Central pain syndrome is a neurological condition caused by damage to or dysfunction of the central nervous system (CNS), which includes the brain, thalamus, brainstem, and spinal cord. The thalamus, in particular, has been implicated as a causative lesion site in as high as 70% of cases presenting with central pain (Bowsher et al. 1998). The characteristics of central pain include steady burning, cold, pins and needles, and lacerating or aching pain although no one characteristic is pathognomonic (Bowsher 1996). Central pain can be associated with breakthrough pain and decreased discriminative sensation. Onset can be delayed, particularly after stroke. There are considerable differences in the prevalence of central pain among the various disorders associated with it. The highest incidence of central pain occurs in multiple sclerosis (MS), stroke, syringomyelia, tumour, epilepsy, brain or spinal cord trauma, and Parkinson’s disease (Boivie 1999; Siddall et al. 2003; Osterberg et al. 2005).

Treatment of central pain syndrome is difficult and often frustrating for both the patient and the practitioner. Anti-depressants and anti-convulsants may provide some relief. Pain medications are generally only partially effective. The functional neurological approach has been as effective as any therapies at decreasing the symptoms of central pain. The approach includes assessing the central integrated state of all levels of the neuraxis and determine how pain modulation may be achieved most effectively. The following questions are helpful as a guide to approaching the treatment necessary for each individual:

The kidney may, under certain conditions, concentrate some components in the urine so that these compounds precipitate out of the urine and form small kidney stones or renal calculi. Small pieces of the stones break off and pass into the ureter that leads from the kidney to the bladder. In size, they are not more than twice the size of the normal diameter of the normal ureter. Pressure builds up behind the plug formed by the stone, tending to drive it into the ureter and, as a result, the muscle in the wall of the ureter goes into localised strong contraction. This band of contraction moves down the ureter to produce peristaltic waves to drive the stone down. During this process called ‘passing a stone’ agonising spasms of pain sweep over the patient in such a way that even the toughest and most stoical of characters usually collapse. The patient is pale with a racing pulse, knees drawn up, with a rigid abdomen and motionless. Even crying out because of the pain is restrained because all movement exaggerates the pain. As the stone passes into the bladder there is immediate and complete relief of the pain resulting in an exhausted patient. The reason for describing this event here is that in physiological terms, and mechanical terms, this is a rather trivial event. Furthermore, it occurs in a structure which is poorly innervated when compared to other areas of the body. This process of passing kidney stones is described by the patient as painful beyond any expectation that pain can reach such intensity (Melzack & Wall 1996).

Several terms are used to describe pain disproportionate to the injury or not appropriate to the stimulus causing the pain.

Hyperalgesia is the term used to describe an excessive response to noxious stimulation. Hyperalgesia can be classified as either primary or secondary in nature. Primary hyperalgesia results from the release of various chemicals at the site of injury, leading to sensitisation of nociceptive afferents. Secondary hyperalgesia involves collateral branches of the nociceptive afferents at the level of the spinal cord, which results in the regions surrounding the site of injury becoming more sensitive to pain.

Allodynia is the term used to describe pain produced by normally innocuous stimulation. For example, stroking the skin would not normally be painful; however, stroking the skin after a sunburn may produce pain. With allodynia there is no pain if there is no stimulus, unlike other types of pain that can occur spontaneously without the presence of a stimulus.

Motorcycle accidents are typically associated with injuries of the head and shoulder. On hitting a solid structure such as the road or a light standard, the rider is catapulted forwards and hits the road or other obstacle at high speed. Crash helmets have effectively decreased head injuries, but the next vulnerable point that hits the road is often the shoulder, which may be wrenched down the back. The arm is supplied by a network of nerves, the brachial plexus, which leaves the spinal cord at the level of the lower neck and upper chest and funnels into the arms. In the most severe of these injuries the spinal roots are avulsed, that is, ripped out of the spinal cord, and no repair is possible. When this type of injury occurs, the arm is commonly paralysed from the shoulder down to the hand. The muscles of the arm become thin and limp with no sensation in the arm. Occasionally, people with this injury have reported feeling a phantom limb, which they can sense very clearly as an entire arm, but which had no relationship to the real arm. These phantom arms seem to be placed in various positions, which do not coincide to the position of the real arm at their side. The phantom arm commonly feels as though it is on fire.

Occasionally, people who have experienced amputations of limbs may feel the presence of that limb even though the limb has been amputated. This is known as phantom pain (Melzack & Wall 1996). This shows that in certain cases pain may persist long after all apparent physical healing has occurred.

The term phantom limb was introduced by Silas Weir Mitchell. It is used to describe malrepresentation of actual limb position or existence following amputation or nerve blocks and is recognised by the patient as an ‘illusion’ rather than being the patient’s delusion (Ramachandran & Hirstein 1998). Phantoms occur in 90–98% of all amputees almost immediately, but less commonly in children.

The intensity of the phantom presence appears to depend on both the degree of cortical representation present and the subjective vividness of that part in one’s body image prior to amputation. The perceived postures of phantom limbs are probably related to the patient’s experience prior to amputation, or may be perceived as maintaining a spastic, causalgic, or dystonic posture. The phantom sensations tend to fade after anywhere between days and decades. Some people experience a bizarre sensation referred to as telescoping in which they perceive a gradual shrinking of the limb so that it remains as only the hand on a stump. It is thought that this may occur due to increased representation of the hand in the brain’s somatotopic maps.

When one part of the body is used more than an adjacent part, the somatotopic representation of that part will begin to expand and the receptive fields of the adjacent lesser utilised region of the cortex will become smaller. When an area of the body is amputated, the area of the brain that normally responds to sensory activation of the amputated body part will then begin to respond to sensory activation of adjacent body parts. This process probably occurs because of thalamocortical arborisation or unmasking of previously seldom used, occult synapses in the cortex.

The reduction in activity experienced by cortical neurons as a result of sensory deprivation reduces the amounts of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) released from interneurons, which in turn may allow previously weak synapses to become disinhibited. These normally suppressed inputs probably originate from long-range horizontal collaterals of pyramidal neurons located in cortex adjacent to the area of cortex that has lost its afferent stimulus due to the removal of the limb (Ramachandran & Hirstein 1998). Conversely, high levels of GABA brought about by persistent intense sensory input can cause weak synapses to become even more strongly inhibited, resulting in a surround inhibition of cortical areas not of immediate concern. In other words, the extensive use of the fingers of the left hand, as would be the case in learning to play the guitar, will ‘focus’ the cortical area representing the fingers of the left hand and inhibit adjacent areas of cortex representing the elbow and shoulder.

Tinnitus, which is the subjective sensation of noise in the ears, has also been referred to as a phantom auditory sensation that may occur due to reorganisation of the auditory cortex following some degree of deafferentation from the cochlea of the inner ear. Cochlear lesions resulting in loss of a specific range of frequencies can lead to reorganisation of the auditory cortex due to replacement of the corresponding cortical areas with neighbouring areas of sound representation (Sexton 2006).

Musical hallucinations have also occurred in patients who have previously experienced tinnitus and progressive hearing loss. The complex nature of these hallucinations supports the theory of central auditory involvement due to deafferentation, despite the fact that hallucinations represent inappropriate overactivity of auditory neurons.

It is often believed that variations in pain experienced for person-to-person is due to different pain thresholds. There are four different thresholds related to pain, and it is important to distinguish between them.

There is now evidence that suggests that the majority of people, regardless of their cultural background, have a uniform sensation threshold. The sensory conduction apparatus appears to be essentially similar in all people so that a given critical level of input always elicits a sensation. The most striking effect of cultural background, however, is on pain tolerance levels. For example, women of Italian descent tolerate less shock than women of American or Jewish descent.

The importance of the meaning associated with the pain-producing situation is made particularly clear in experiments carried out by Pavlov on dogs. Dogs normally react violently when they are exposed to electric shocks to one of their paws. Pavlov found, however, that when he consistently presented food to a dog after each shock the dog developed an entirely new response. Immediately after each shock the dog would salivate, wag its tail, and turn eagerly towards the food dish. The electric shock now fails to evoke any responses indicative of pain and has become a signal meaning that food was on the way. This type of conditioned behaviour was observed as long as the same paw was shocked. If the shocks were applied to another paw the dog reacted violently. This study shows very convincingly that stimulation of the skin is localised, identified, and evaluated before it produces perceptual experience and overt behaviour (Melzack & Wall 1996). The meaning of the stimulus acquired during earlier conditioning modulates the sensory input before it activates brain processes that underlie perception and response.

If a person’s attention is focused on a painful experience the pain perceived is usually intensified. In fact, the mere anticipation of pain is usually sufficient to raise the level of anxiety and thereby the intensity of the perceived pain. In contrast, it is well known that distraction of attention away from the pain can diminish or abolish it. This may explain why athletes sometimes sustained severe injuries during the excitement of the sport without being aware that they have been hurt.

The power of suggestion on pain is clearly demonstrated by studies using placebos. Clinical investigators have found that severe pain such as postsurgical pain can often be relieved by giving patients a placebo (usually some non-analgesic substance such as sugar or salt in place of morphine or other analgesic drugs). About 35% of the patients report marked relief of pain after being given a placebo (see below).

When psychological factors appear to play a predominant role in a person’s pain, the pain may be labelled as psychogenic pain. The person is presumed to be in pain because they need or want it.

The pain produced by nociceptive mechanisms involves direct activation of nociceptors. This is the commonly understood mechanism of pain production, where receptors sensitive to damage-causing activities, classified as nociceptive receptors or nociceptors, are stimulated and transmit excitatory information to the substantia gelatinosa neurons of the dorsal horn for integration and processing.

Neuropathically produced pain involves direct injury to nerves in the peripheral nervous system (PNS) or the CNS which has a burning or electric quality. Some examples of syndromes or conditions where neuropathic pain is thought to be involved include complex region pain syndrome (CRPS) (see below), post-herpetic neuralgia, phantom limb pain, and anaesthesia dolorosa, which is a condition where pain is perceived in the absence of sensation following treatment for chronic pain. Some neuropathic pains are thought to be sustained, at least in part, by sympathetic efferent activity via the expression of alpha-adrenergic receptors on injured C-fibres (see below).

Inflammatory pain is related to tissue damage. Damage to neurons can result in the release of neurotransmitters, and neuropeptides that can result in neurogenic inflammation. The proinflammatory substance prostaglandin E2 (PGE2) is released from damaged neurons and other cells. PGE2 is a metabolite of arachidonic acid via the cyclo-oxygenase pathway. The cyclo-oxygenase enzyme can be blocked by the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin and is thought to be the mechanism by which these medications exert their effect. Bradykinin, which is also an extremely active proinflammatory and pain-activating substance, is also released when tissue is damaged. Bradykinin activates Ad and C fibres directly and causes synthesis and release of prostaglandins from nearby cells.

Other proinflammatory substances released following injury include substance P and calcitonin-gene-related-peptide (CGRP), which both act on venules to spread inflammation and release histamine from mast cells.

Pains of brief duration are usually recognised as having little consequence and rarely produce more than fleeting attention. These momentary transient pains are often felt as two types of pains. For example, if you drop a heavy book on your foot you experience an immediate pressure-type sensation, followed by the secondary pain that will arrive shortly and when it does it wells up in your consciousness and obliterates all thoughts for the moment.

The characteristics of acute pain are tissue damage, pain, and anxiety. Acute pain is usually related to an identifiable injury or disease focus and self-limited, resolving over hours to days or in a period associated with a reasonable period for healing. It is generally composed of the transitional period between coping with the cause of the injury and preparing for recovery. It is usually of short duration of days to weeks. Acute pain usually responds well to treatment. An injury should be considered to be in the acute phase during the natural history of normal healing for that injury. For example, the natural history of healing for a broken bone could be expected to range from 4 to 6 weeks. Pain experienced during the initial 4–6 weeks should be thought of as acute. However, if pain persists for longer than 6 weeks, the chronic classification should be applied.

This type of pain persists even after all possible physiological healing has occurred. It is no longer a symptom of injury but a pain syndrome. It may reflect separate mechanisms from the original insult and not reflect actual tissue damage or focal disease. The patient will often use vague descriptions of pain with difficulty in describing timing and localisation of the pain.

Patients are beset with a sense of hopelessness or helplessness and often the pain is described in terms that have emotional associations. Marked alteration in behaviour with depression and/or anxiety often result, which may reflect a more cognitive aspect of pain. This condition is usually present for months to years in duration, with the patient experiencing marked reduction in daily activities, excessive amounts of medications, fragmentation of medical services, history of multiple non-productive tests, treatments, and surgeries.

A placebo is a substance or procedure thought to have no intrinsic therapeutic value which is given to an individual to satisfy a physiological or psychological need for treatment. The effects of placebos often produce the same or better results than treatments thought to have an intrinsic value. It was once thought that the effects of placebo were predominantly psychosomatic but current research has revealed that the placebo is indeed a real effect. For example, placebo analgesia can be blocked by naloxone, an opioid antagonist, suggesting that endogenous analgesia systems are likely to be activated during placebo analgesia.

The gold standard in best practice therapeutics is that the treatment should significantly outperform the placebo effect in order to be considered a viable option for therapy. In the treatment of pain, production of analgesia or loss of pain sensation is the desired effect (Zhuo 2005).

As mentioned above, endogenous analgesia systems are a likely component of the placebo effect. The anterior cingulate gyrus (ACC) has been found to be involved in this placebo analgesia. It has been theorised that ACC activation is responsible for facilitating descending inhibitory systems. However, electrical stimulation or glutamate synaptic activation in the ACC has actually been observed to increase nociceptive reflexes at the level of the spinal cord, and enhanced synaptic transmission and long-term plasticity have been found in ACC neurons after tissue injury, which suggests that the ACC may actually enhance any existing nociceptive effects. This would act in the opposite of the placebo effect and actually increase pain! Several theories have been advanced to incorporate these findings into a model that still allows the involvement of the ACC as a component in the generation of the placebo effect (Zhuo 2005).

The first theory involves the inhibition of pain-producing neurons in the ACC. Many neurons in the ACC respond to acute pain and the amount of this activation is related to pain unpleasantness. Activation of inhibitory neuron in the ACC can affect the excitability of these neurons by releasing GABA onto their postsynaptic receptors. Consequently, the excitability of ACC neurons is reduced, and neurons respond less to noxious stimuli.

The second theory involves the activation of local opioid-containing neurons in the ACC. Similar to the first theory, neurons containing opioid peptides may be activated. Opioid may act presynaptically and/or postsynaptically to inhibit excitatory synaptic transmission and reduce neurons responses to subsequent peripheral noxious stimuli. This mechanism could explain the fact that some placebo effects are sensitive to blockade by naloxone.

A third possibility involves the inhibition of descending facilitatory modulation from the ACC. The release of the inhibitory neurotransmitter GABA and/or opioids will reduce the excitability of ACC neurons that send descending innervations directly or indirectly to rostral ventral medulla (RVM) neurons. Consequently, descending facilitatory influences will be reduced.

The final theory involves a mixed activation of excitatory and inhibitory transmission by placebo treatment with the net result within the ACC being reduced excitatory transmission.

The description of CRPS dates back to at least 1864 when Mitchell first described this condition. Mitchell coined the term ‘causalgia’, meaning burning pain. The most striking feature of this condition is pain that is disproportional to an injury. The onset of CRPS typically follows minor injuries such as sprains, fractures, or surgery. Other names for this condition include:

Due to confusion arising from the many names for this set of symptoms, the International Association for the Study of Pain (IASP) developed nomenclature to more accurately describe chronic pain. IASP coined the term chronic regional pain syndrome and broke CRPS into two categories;

The key symptom of CRPS is continuous, intense pain out of proportion to the severity of the injury, which gets worse rather than better over time. CRPS most often affects one of the arms, legs, hands, or feet. Often, the pain spreads to include the entire arm or leg. Typical features include dramatic changes in the colour and temperature of the skin over the affected limb or body part, accompanied by intense burning pain, skin sensitivity, sweating, and swelling.

The cause is unknown but CRPS affects from 2.3 to 3 times more women than men and is a major cause of disability in that only one in five patients is able fully to resume prior activities. Equally frightening is the increasing diagnosis of CRPS in children and adolescents; although there have been no large-scale studies on the incident of CRPS in children, some generalisations can be made about the children who get this condition. Published case studies indicate that the incident of CRPS increases dramatically between 9 and 11 years old, and it is found predominantly in young girls.

A recent web-based epidemiological survey of 1610 people with CRPS, sponsored by the Reflex Sympathetic Dystrophy Association of America (RSDSA) and conducted by Johns Hopkins University, showed that common events leading to the syndrome were surgery (29.9%), fracture (15%), sprain (11%), and crush injuries (10%). There have also been some reports of increased occurrence of CRPS following the administration of general anaesthetic.

Nearly all drugs currently used during the course of general anaesthesia may lead to hypersensitivity reactions of various types. There may be an acute type I allergic reaction or a more or less severe pseudoallergic reaction, in rare cases with lethal outcome.

In some cases the sympathetic nervous system has been implicated as an important component in sustaining the pain. These abnormal changes in the sympathetic nervous system seem to be responsible in some patients for constant pain signals to the brain, which alters the cortical areas of their brain responsible for pain and sensory reception of those areas of the body. Abnormal function of the sympathetic nervous system can also lead to movement disorders. Recent evidence, however, does not support that the pain of CRPS is solely sympathetically mediated; therefore, a thorough investigation examining the central integrated state of all levels of the neuraxis should be undertaken to determine the true nature of the patient’s persistent or severe pain syndrome. An updated theory concerning the mechanism behind CRPS is that it is caused by supersensitivity of sympathetic nerve neurotransmitters and their metabolites (Rowbotham et al. 2006). Patients with CRPS have been found to have decreased concentrations of norepinephrine in the venous effluent of the affected limb. This suggests that it is not due to increased output of the sympathetic nervous system. CRPS patients have increased concentrations of bradykinin and other local non-specific inflammatory mediators. Sympathetic inhibition may lead to up-regulation of beta-adrenergic receptors on the peripheral nociceptive fibres, making the afferents more sensitive to normal or lower levels of the neurotransmitter. It is more common to observe an initial increase in skin temperature followed by a chronically decreased skin temperature and trophic changes later in the course of the condition. The generation and maintenance of central sensitisation are dependent on the actions of transmitter/receptor systems in the peripheral cord. Activation of receptor systems and second messenger systems leads to changes in receptor sensitivity, which increases the excitability of neurons (Schaible et al. 2002). This is a form of physiological wind-up.

This process can be summarised into six steps:

Pain is not the only reason why patients have difficulty moving. Patients state that their muscles feel stiff and that they have difficulty initiating movement.

Paediatric patients present unique challenges. For example, children have not had sufficient time to develop the psychosocial skills necessary to cope with the pain and suffering due to CRPS. The fear and anxiety that this syndrome produces in a child leads to a further lowering in the child’s pain threshold, making activities of normal life even more painful. The presence of these seemingly unexplainable symptoms has led to a great deal of confusion and frustration among children and their families. Another theory is that CRPS is caused by a triggering of the immune response, which leads to the characteristic inflammatory symptoms of redness, warmth, and swelling in the affected area (Romanelli & Esposito 2004).