Why do animals have a nervous system?
The nervous system (NS) is a complex collection of cells that transmits and integrates signals to control the movement. Structurally, the NS may be divided in central nervous system (CNS) and peripheral nervous system (PNS). The CNS is made up by the encephalon and the spinal cord, whereas the PNS is formed by the nerves. Functionally, the NS it is divided in two components: somatic and visceral. The somatic component of the NS regulates the muscles and the skin, and the visceral component or autonomic nervous system (ANS) regulates the normal function of the structures with involuntary control, like the heart, smooth muscle and glands maintaining homeostasis.
The CNS is divided into two parts: the brain (encephalon) and the spinal cord. The parts of the brain are: cerebrum, cerebellum and brain stem. In the clinical setting, the terms forebrain, midbrain and hindbrain are commonly used. The forebrain refers to the prosencephalon, formed from the diencephalon and the cerebral hemispheres (telencephalon). The midbrain refers to the mesencephalon. The hindbrain refers to the rhombencephalon, and consists of the pons, the medulla oblongata and the cerebellum.
The PNS refers to the cranial and spinal nerves with their associated ganglia (somatic and autonomic). The fibers forming the PNS may be afferent (sensory) and/or efferent (motor) component. The afferent fibers transmit impulses from somatic or visceral body structures to the CNS. The bodies of afferent neurons are grouped together forming cranial and spinal ganglia. Efferent fibers transmit the impulses from the CNS to a striated muscle (somatic component), and smooth, muscle gland and internal organs (visceral component). Their bodies are grouped, forming nuclei in the brain stem and in the spinal cord.
The name given to the efferent neuron of the peripheral nervous system which connects the CNS with the musculoskeletal apparatus is motor neuron or lower motor neuron (LMN). The motor neurons are of two types: alpha motor neurons and gamma motor neurons. The alpha motor neurons innervate the extrafusal muscle fibers and the gamma neurons innervate the intrafusal muscle fibers. In the ANS, the efferent system involves two neurons: a preganglionic neuron and a postganlionic neuron. The first neuron has the soma located in the CNS, and the axon synapses with a second one outside the CNS. The soma of the postganglionic neurons is grouped in autonomic ganglia. Some authors refer to the postganglionic neuron as a LMN and to the preganglionic neuron as interneuron.
The nerves are formed by fibers that can be either axons or dendrites. So, motor neurons in the PNS are formed by axons. In the case of the sensory nerves that run from the receptor to the ganglion is formed by dendrites, while the part from the ganglion to the CNS is formed by axons. The nerve fibers are surrounded by loose connective tissue, the endoneurum, and grouped in bundles separated from each other by the perineurium. The fiber bundles are surrounded by a layer of connective tissue called the epineurium. The nerve fibers may be myelinated or unmyelinated.
Lower motor neuron clinical signs
An injury affecting the LMN may be located at four levels: central nervous system, nerve roots, nerve branches or motor end plate. The clinical signs are: muscular weakness with paresis or paralysis, hypotonia with absent (areflexia) or diminished reflexes (hyporeflexia) and neurogenic atrophy.
In sensory neuropathies and in myopathies, the clinical signs are similar to those of an injury of the LMN. Given that a motor neuron requires a minimum number of active synaptic connexions in order to work, a sensory neuropathy produces a decrease in the number of afferent signals resulting in hypotonia.
The concept of the upper motor neuron (UMN) system refers to the neurons located entirely within the CNS. They are responsible for the activation and inhibition of the LMNs in voluntary and involuntary movements, and for maintaining muscle tone in order to retain balance and control posture.
Upper motor neuron clinical signs
Disfunctions in the UMN system cause different degrees of paresis with hypertonia, stiff gait (spasticity), and exaggerated reflexes (hypereflexia) due to the loss of the regulating function of the UMN over the muscle tone and reflexes.
Given that the UMN acts on the extensor and flexor muscles, how can we explain the increase in extensor muscle tone with spasticity and hypereflexia? The answer must be sought at the LMN level and by the absence of inhibitory signals coming from the descending tracts. Any stimulus produced at the intrafusal level results in an increase of muscle tone in the extrafusal fibers of the same muscle. As the extensor muscles have a greater tone than the flexors to maintain posture and resist gravity, they receive a larger number of gamma motor neurons and possess more muscle spindles. Thus, with UMN lesions, a loss in regulation of the myotatic reflex results in an extensor tone greater than the flexor one.
The function of the NS
The main function of the NS is to react to stimuli and to coordinate motor activity with the purpose of having smooth and skilled movements, to fight gravity, and keep the individua alive. These mechanisms may be activated unconsciously, through reflexes, or consciously. The reflexes are a primary survival mechanism however conscious control is necessary to perform dangerous movements. In order to do that, a part of the NS has to be deeply involved in generating thoughts, feelings and memories as they are of vital importance to avoid nasty experiences from the past, and to make good choices to avoid dangerous situations.
The pathways needed to generate a movement are the input and the output. Sensory (afferent) information coming from the outside or inside the body, reaches integration centers located in the CNS. Then, after processing the information, motor signals (efferent) reach the effector organs. These two pathways, afferent and efferent, are located in the CNS, forming tracts and lemnisci, and in the PNS forming nerves.
For a smooth integration of the sensory and motor signals, impulses have to reach centers located in the brain. Depending on the skill capacity of movements among species, these coordination centers are being more or less developed.
For performing basic movements, the integration centers in the brain have to be present and equally developed in all kind of species. The CNS structures that all of them share are similar among vertebrates. This basic structures are located in the brain stem and in the spinal cord. In these two parts of the CNS, the organization is primitive. In the spinal cord, the arrangement of gray and white matter follow a basic pattern: gray inside, and white outside. However, in the brain stem, neuroblast cells from the mantle layer are displaced to a more external localization.
The parts of the CNS that, due to their higher integration functions, need more neurons are the cerebrum and the cerebellum. In them most of the neurons are located on the periphery, forming the cortex, and included in the white matter, forming nuclei. The more cognitive and skilled functions are needed, the bigger the cerebrum and the cerebellum are. Being the most developed in the primates.
For skilled movements of hands and feet, direct connections are needed between higher centers (cerebrum and cerebellum) and motor neurons. The so called pyramidal system or corticospinal tract is in charge of these activities. This system is better developed in primates and, among the rest of mammals, in cats. The pyramidal or corticospial tract is a large inhibitory pathway. More than 80% of axons have an inhibitory effect on motorneurons. This inhibition enables the execution of fine movements and reciprocally inhibits the antagonistic muscles to the voluntary movement. A great percentage of corticospinal fibers decussate (pyramidal decussation) in the caudal portion of the medulla oblongata, and form the lateral corticospinal tract in the lateral funiculus of the spinal cord. These fibers control the distal limb muscles. The fibers that not decussate in the pyramidal decussation, form the medial corticospinal tract that runs caudally in the ventral funiculus of the spinal cord. In its pathway along the ventral funiculus, fibers from the medial corticospinal tract cross the midline in the white commissure of the spinal cord, and synapse on interneurons that control the proximal muscles of the limbs. The corticospinal fibers synapse on interneurons of laminae V, VI and VII. In humans, monkeys and raccoons they synapse on alpha motorneurons of lamina IX. They influence flexor muscles being excitatory over alpha motorneurons, and extensor muscles being inhibitory over extensor motorneurons. Most of the pyramidal fibers synapse on the cranial nuclei and form the corticonuclear tract (poorly developed in the cat), in the mesencephalic tectum and tegmentum, in the red nucleus, in the pontine nuclei (corticopontine tract), and in the reticular formation.
For less skilled movements, the extrapyramidal system is in charge. Among the extrapyramidal tracts, the rubrospinal tract controls the proximal parts of the limbs. In cats, the red nucleus receives corticorubral fibers from the sensory cortex that are important in contact placing. The reticulospinal and the vestibulospinal tracts, control the muscles of the trunk and neck, and the antigravitatory muscles of the limbs.
The vestibulospinal tract is formed by a lateral and medial tracts. The lateral vestibulospinal tract is formed by axons that descend from the lateral vestibular nucleus to ipsi- and contralateral interneurons (lamina VII and VIII) and motor neurons (IX) in the ventral horn. The medial vestibulospinal tract is formed by axons from the rostral, medial and caudal vestibular nuclei that reach cervical spinal cord segments. The fibers of the medial vestibulospinal tract travel in the medial longitudinal fasciculus in the brain stem and in the ventral funiculus, up to cervical spinal cord segments. The end on interneurons of lamina VII and VIII).
The reticulospinal tract comes from the reticular formation of the pons and medulla oblongata.. The pontine reticulospinal tract is formed by fibers from the pontine reticular formation that descend in the ipsilateral ventral funiculus to end in ipsi- and contralateral motorneurons of the ventral horn. Being faciliatory to extensor muscles. The fibers of the medullary reticulospinal tract originate in the reticular formation of the medulla oblongata and descend bilaterally in the lateral funiculus of the spinal cord to inhibitory motorneurons to extensor muscles. The spinoreticular fibers in cats end at all leaves of the spinal cord in laminae I, V, VI, VII, VIII, IX and the cervical nucleus.
The tectospinal tract originates from the rostral colliculus, and receives fibers from the caudal colliculus. The axons cross de midline at the dorsal tegmental decussation and join the medial longitudinal fasciculus, to continue in the ventral funiculus of the cervical spinal segments and first thoracic ones. They end on interneurons in laminae VI and VII. They are responsible for the turning of the head towards visual and auditory stimuli.
The role of the rubrospinal system is to allow the initiation of movement, acting mainly over interneurons that synapse on motor neurons that innervate flexor muscles. The rubrospinal tract is almost absent in humans. The red nucleus has a facilitatory effect on the contralateral alpha motor neurons to flexor muscles and inhibitory on the contralateral alpha motor neurons to extensor muscles. In all mammals and birds that have been studied, the tract crosses in the ventral tegmental decussation and descends in a position ventral to the spinal trigeminal tract and lateral to the superior olive and facial nucleus. The rubrospinal tract is well stablished in cat and monkey and extends the length of the spina cord. The fibers synapse on interneurons in the dorsal part of lamina VII and in laminae V and VI. It is important to point out that the red nucleus has afferences from the cerebellum and from the cerebral cortex, being significantly important the ones that come from the interpositus nucleus of the cerebellum. The regression of the rubrospinal tract was a consequence of taking up corticospinal systems in the control of forelimb muscles, in bipedal species. The role of the pontine, reticulospinal, and vestibulospinal tracts is concerned on fighting against gravity, by acting on extensor muscles. The pontine reticulospinal tract acts on gamma (to a lesser extend on alpha) excitatory motorneurons that innervate extensor muscles. The vestibulospinal tract is excitatory, trough interneurons, to ipsilateral alpha (to a lesser extend gamma) motorneurons, and inhibitory to contralateral motorneurons. The medullary reticulospinal tract opposes the antigravitatory muscles by inhibiting the gamma motorneurons that innervate extensor muscles.
The difference between primates and the rest of mammals is the grade of development of the pyramidal system. It has been pointed out that the regression of the rubrospinal tract in humans is a consequence of taking over of the corticospinal tract (pyramidal). It has been proved that when the corticospinal tract (pyramidal system) is damaged in humans, the role of the poorly developed rubrospinal tract, takes over. In the domestic mammals the rubrospinal tract is more developed than in humans. This explains why non primates have less fine movements of hands and feet than the primates. In horses, ruminants and pigs the corticospinal tract reaches only the cervical spinal segments. In non primates, the parts of the body that require skilled movements are the mouth and eyes. This are controlled by the pyramidal system, through the corticonuclear tract.
The antigravitatory tracts must act constantly to fight gravity so these have to be constantly inhibited. This regulatory activity comes from the cerebellum and from the cerebrum. The lateral vestibulospinal tract, that also increases its activity by vestibular stimuli, is inhibited from the cerebellum. Inhibitory (GABA) Purkinje neurons of the paravermis of the rostral lobe of the cerebellum reach the lateral vestibular nucleus (Dietrich nucleus) through the corpus juxtarestiforme (medial portion of the caudal cerebelellar peduncle) and inhibit its facilitating activity over extensor muscles. The medullary reticulospinal tract is inhibitory over the extensor (antigravitatory) muscles. This tract has to be constantly activated through prosencephalic descending neurons. When decerebellate (alpha rigidity) or decerebrate (gamma rigidity) postures are clinically presented, pathologies affecting these inhibitions over centers that control antigravitatory muscles must be suspected.
The above mentioned extrapyramidal centers in the brain stem receive stimuli from the cerebrum in order to activate voluntarily, and from the cerebellum to control its activity. The projection fibers from the motor cortex of the cerebrum form part the internal capsule to become the corticospinal and corticonuclear tracts acting on extrapyramidal centers that are the starting point of extrapyramidal tracts.
Function of the motor systems
According to its location and destination, it is possible to stablish a somatotopical organization of the descending motor systems. The tecto and tegmentospinal tracts coordinate the head, neck and eyes in response to visual or auditory stimuli. The reticulospinal and vestibulospinal tracts act on axial and appendicular muscles to control muscle tone. The rubrospinal tract acts on proximal muscles of limbs, and the corticospinal tract acts on distal muscles of limbs. Both, rubrospinal and corticospinal, are involved in the execution of voluntary movement.
The descending tracts (UMN) end in alpha (α) and gamma (γ) motor neurons. The γ motor neurons innervate the intrafusal fibers, and the α motor neurons the extrafusal fibers. These motor neurons are activated by descending tracts (UMN) and by afferents neurons (types II, Ia and Ib) from intrafusal fibers. In the presence of an UMN lesion there is extensor hypertonia. If the the dorsal root (afferent fibers) is sectioned, the the clinical signs are abolished. This means that the extra activity of the gamma motor neurons is the cause of the rigidity. In this case, the rigidity is considered a gamma rigidity. If the rigidity does not disappear, means that the cause of the rigidity is an extra activity of the alpha motor neurons. Then, the rigidity is considered an alpha rigidity.
Decerebrate vs decerebellate rigidity
The decerebrate posture is caused by a severe mesencephalic lesion located at the level of the red nucleus or between the red nucleus and the vestibular nuclei. In this situation, the descending excitatory neurons of the rubrospinal tract are damaged and the prosencephalic control over the medullary reticular formation (inhibitory over extensor muscles) is inhibited. Additionally, the reticular activating system over the cerebrum is disappears resulting in diminished or absent consciousness. On the other hand, the pontine reticular tract (excitatory over extensor muscles) does not receive inhibitory action from upper centers and, together with the vestibulospinal tract, keep exerting their excitatory action over the extensor muscles. The resulting effect is a rigid extension of the limbs and opisthotonus. This rigidity is considered a gamma rigidity.
When a similar situation of opisthotonus is observed with rigid extension of the forelimbs but and flexion of the hips without impairment of consciousness, a decerebellate posture must be considered. This is caused by a damage in the rostral lobe of cerebellum or in the inhibitory efferent cerebellar fibers. This situation causes an increase of the lateral vestibulospinal tract activity over the extensor muscles. This rigidity is considered an alpha rigidity. The decerebellate animal may present the hind limbs flexed or extended depending on the cerebellar lobes affected. If only the rostral cerebellar lobe is damaged, there is an extension of the fore limbs. If the posterior lobe is also damaged, the hind limbs may be also extended. But the hip is always flexed.
The flexion of the hip is caused by contraction of the iliopsoas muscle. This muscle is used to stabilize the column when the pelvic limbs are fixed, and to initiate the movement of propulsion in quadrupeds by pulling forwards the femur. As the cerebellum helps to stabilize the column by inhibiting the tone of the hypaxial muscles, a lesion of the cerebellum causes a contraction of the iliopsoas muscle.
Considering the prosencephalon
Cerebrum and diencephalon (specially the thalamus) have to be considered as a single unit because they are involved in the same function of being an upper center for motor coordination.
The main functions of the cerebrum are: sensory, will and thoughts. The primary motor cortex of the cerebrum is only important in animals that have a well developed pyramidal system (primates). Lesions affecting the prosencephalon impair the above mentioned functions, with loss of attention, misbehaviour and diminished consciousness, and slow or absent proprioceptive reactions due to a diminished sensory function. However, the movements that do not require will may not be affected as these movements are elicit by the brain stem and/or spinal cord. In order to move properly, memories are needed. Experiences of the past help to avoid undesirable situations. Remembering is another important function of the cerebrum. In order to do this, interrelation between different parts of the cerebral hemispheres are needed.
A special group of nuclei are present in the cerebrum, the basal nuclei. These nuclei function as a system to allow wanted movements and impede unwanted ones. They are also involved in behavior. One of them, the amygdala, is located ventromedially to the insular cortex inside the piriform lobe related with behavior. Concerning the motor function, the basal nuclei have connections with the cerebral cortex, thalamus, substantia nigra and subthalamus. When sensory information reaches de cerebral cortex, cortical excitatory fibers activate the striated body. This, in turn, projects inhibitory signals to the pallidum. The medial portion of the pallidum activates the thalamus, whereas the lateral portion of the pallidum inhibits it. The cerebral cortex, the striated body and the thalamus also activate the dopaminergic neurons of the pars compacta of the substantia nigra. This inhibit the basal nuclei. This complex circuitry regulates the signals that have to be transmitted from the motor cortex to brain stem centers and to the spinal cord facilitating the movements and preventing unwanted ones. In the center of these circuit, the thalamus plays a key role. This explains the origin of the word thalamus meaning internal chamber. Animals presenting lesions in the basal nuclei show uncoordinated movement with unwanted movements (as tremor) and misbehavior. In that sense, the compulsive circling movement may be a misbehavior sign. In humans many of the movement disorders (as myoclonus) may be originated by wrong connections at the level of the motor cortex with extrapyramidal cerebral nuclei (basal nuclei) and substantia nigra. However, as de Lahunta proposes, in animals, the origin of these undesired wrong movements may involve the pacemaker or movement generator located at the level of motor neuron (LMN).
Considering the cerebellum
The cerebellum coordinates the movement through connections with the prosencephalon, and centers of the brain stem. The brain stem centers are involved in keeping the muscle tone in order to fight gravity. The part of the cerebellum related with the prosencephalon is the cerebrocerebellun or neocerebellum, and the dentate and interpositus nuclei. The part of the cerebellum involved in keeping the muscle tone forms the paleocerebellum or spinocerebellum and the fastigial nucleus. The part of the cerebellum directly implicated in the equilibrium is the vestibulocerebellum (flocculonodular lobe).
According to the previous phylogenetic classification of the cerebellum, lesions of the neocerebellum may cause cerebellar hypermetria and intention tremor. Lesions of the paleocerebellum may cause increase of the tone of the antigravitatory muscles and titubation. Lesions in the vestibulocerebellum may cause loss of balance.
In relation to the increase of muscle tone, we should consider the antigravitatory limb muscles and the hypaxial muscles. The first ones help the animal to maintain a stand position, and the last ones prevent the column from collapsing ventrally. In that sense, contraction of lumbar hypaxial muscles compensate the ventral flexion of the column. When cerebellar lesions diminish the inhibitory action over the hypaxial muscles, a dorsally curved column may be present with a flexed hip (the iliopsoas muscle is responsible for this situation). On the other hand, the epaxial muscles are responsible for the propulsion, the stance of the animal and holding the head.
When the lesion affects the flocculonodular lobe, vestibular signs may be present. These include loss of balance, head tilt and nystagmus. Head tilt requires a specific explanation: when the animal turns the head towards one side, the excitation of the lateral vestibular nucleus increase the tone of the ipsilateral extensor muscles to keep the balance (through the lateral vestibulospinal tract), and the eyes turn towards the turned side of the head (mediated by the medial longitudinal fasciculus). This is the slow phase of nistagmus that will be followed bay a quick phase in the opposite direction. The rostral, medial and caudal vestibular nuclei cause the head to tilt to the opposite side in order to keep the balance of the body (trough the medial vestibulospinal tract). This contralateral tilting of the head is a swinging movement coordinated with the increase of tone of the extensor muscles. As the rostral, caudal and medial vestibular nuclei receive inhibitory fibers from the flocculonodular lobe of the cerebellum, a lesion in this lobe may cause an increase of activity of these nuclei causing a tilt of the head to the opposite side of the lesion. This presentation is named paradoxical vestibular syndrome.
Voluntary movement is generated through cognitive (cerebral cortex) and emotional (limbic) components, and automatic movement (position and balance) through motor centers of the brain stem and spinal cord. External and internal sensory stimuli are transmitted to the central nervous system where they are processed to trigger movement. Memory plays a relevant role in this process in order to adapt movement to learned or unknown situations.
The movement is controlled by networks of central pattern generators (CPGs) that determine appropriate sequences of muscle activation. They are located in the prosencephalon (basal nuclei), brain stem (subthalamus, midbrain, reticular formation) and in the spinal cord (one for each limb that are synchronized). The brain CPGs act on the spinal cord CPGs. The CPGs are controlled by reflexes. However they may be activated in voluntary movements generated by the cerebral cortex. The cerebral cortex is needed only in fine movements and visuomotor coordination (locomotor coordination in unfamiliar locations). The CPGs are responsible for basic movements (eating, breathing, fight, and basic locomotion). For this reason, the “walking therapy” is useful in reactivating the CPGs after a mild spinal cord injury.
In cats, when a lesion is located between the subthalamus and specific nuclei of the midbrain or mesencephalon (the cuneiform nucleus and the pedunculopontine tegmental nucleus), the movement is triggered just by electrical stimulation of these nuclei. However, when the lesion is located rostral to the subthalamus the cat can spontaneously initiate movements. The mesencephalic locomotor nuclei have direct connections with movement centers as the locus coeruleus (activate muscle tone) and pontomedullary reticular formation (controls asymmetrical postural reflexes by regulating different types of muscles). The cuneiform nucleus elicits movement, and the pedunculopontine tegmental nucleus suppresses muscle tone via the reticular formation. These nuclei appear to be present in all classes of vertebrates and must maintain connection with the subthalamus to generate gait. In both cases the walking is neither goal-directed nor adaptative to the environment.
In domestic animals, the cerebral cortex and the basal nuclei seem to be not as important in movement generation as they are in primates. When experimental or natural lesions destroy the motor cortex or the adjacent internal capsule, or the basal nuclei, the gait generation is not impeded. However, the postural reactions are delayed contralateraly. This may be due to a lack of correlation between general proprioception and motor activity. According to de Lahunta, these cases shouldn’t be considered hemiparesis or hemiplegia unless there is a partial or complete motor deficit. The animals that present general proprioception deficit with preserved motor activity, the lesion should be located in the prosencephalon. When there is motor impairment (paralysis or paresis), the lesion should be located caudal to the prosencephalon. We are not considering neither the fine movements nor the accuracy of the movement as these fine movements are controlled by the pyramidal system. Some authors point out the possibility that the association cortex is a memory-related motor-planning generator that triggers the activity of the frontal motor cortex.
The basal nuclei and the cerebellum are connected with the cerebral cortex and thalamus in order to modulate and coordinate fine movements. They program the execution of movement, and control behavior (lesions in the basal nuclei in animals lead to present compulsive movements). The connections of the accumbens with the limbic system control the locomotor behavior in rewarding experiences. For its part, the substantia nigra regulates the activity of the basal nuclei by receiving influences from the cerebral cortex, the thalamus and the striatum (caudate nucleus and putamen).
When the motor cortex sends impulses, through the internal capsule, towards the brain stem and spinal cord, its functions have already been modulated. First, sensory information reaches the thalamus and the cerebellum, and the cerebellum also projects to the thalamus. In turn, the thalamus projects to the sensory cerebral cortex. The sensory cortex contacts the association cortex for integration, and with the archicortex for memory. From there, information reaches the motor cortex. Among these connections, the basal nuclei receive afferences from the entire cerebral cortex and from the dentate nucleus of the cerebellum. They are also connected with the subthalamus and substantia nigra. Once the information has been modulated in this circuit cortico-thalamo-basal nuclei-subthalamus-substantia nigra, it reaches the thalamus again and returns to the motor cortex for starting the motor activity. The projection fibers from the motor cortex act on brain stem nuclei and on spinal cord motor neurons. This complex motor system, in addition to the cerebelovestibular system that help to maintain antigravitatory postures, is responsible for the execution of the movements.
In order to have a good accuracy of movement, associative fibers communicate the occipital (visual), parieto, and frontal (motor) cortices for anticipatory adjustments of posture. Again, short and lasting memory plays a key role to adapt. This is particularly necessary in quadrupeds when avoiding to an obstacle that is no longer in the visual field by the time the hindlimbs are stepping over it. Also the fastigial nucleus of the cerebellum receives information from visual cortex for an error-correction mechanism to control posture by muscle tone.
The general proprioception system is a sensory system that informs the brain about the static position and kynesthesia (reveals the movement of a limb).
. Hind limb:
Myelinated fibers coming from the Golgi tendon neurons reach the thoracic nucleus (from T1 to L4 in lamina VII). Second order neurons cross the mid-plane, through the white commissure and incorporate to the contralateral lateral funiculus, forming the ventral spinocerebellar tract that enters the cerebellum through the rostral cerebellar peduncle.
Myelinated fibers coming from the Golgi tendon neurons and intrafusal receptors reach laminae V, VI and VII of the sacral and lumbar segments. Second order neurons incorporate to the ipsilateral lateral funiculus forming the dorsal spinocerebellar tract that reaches the cerebellum through the caudal cerebellar peduncle.
. Fore limb:
Myelinated fibers coming from the Golgi tendon neurons reach laminae V, VI and VII of the cervical dorsal horn. Second order neurons incorporate to the ipsilateral lateral funiculus giving rise to the cranial spinocerebellar tract. This tract is located medially to the ventral spinocerebellar tract. Their fibers enter the cerebellum through the rostral and caudal cerebellar peduncles.
Myelinated fibers coming from intrafusal receptors enter directly the ipsilateral dorsal funiculus and form the cuneate fascicle reaching the lateral cuneate nucleus. Second order neurons reach the cerebellum through the caudal cerebellar peduncle.
. Hind limb:
Collaterals from myelinated fibers coming from the above mentioned receptors, enter the dorsal funiculus becoming the ipsilateralvgracile fascicle. At the thoracolumbar level, most of the fibers abandon the dorsal funiculus in order to reach the thoracic nucleus (In lamina VII between T1 and L4). Second order neurons become incorporated to the dorsal spinocerebellar tract in the ipsilateral lateral funiculus. At the medulla oblongata, these fibers reach the Z nucleus (it is the medial portion of the gracile nucleus). The fibers that have not abandoned the gracile fascicle reach the gracile nucleus.
. Fore limb:
Collaterals from myelinated fibers coming from the above mentioned receptors enter the dorsal funiculus and become part of the ipsilateral cuneate fascicle reaching the medial cuneate nucleus.
Second order neurons from the Z nucleus, gracile nucleus and medial cuneate nucleus decussate forming the deep arcuate fibers and become the medial lemniscus that reaches the contralateral thalamus.
Pain is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (International Association for the Study of Pain). However, nociception is the reception, conduction and processing of painful information. It involves specific receptors and pathways.
Other related pain definitions are: dyaestesia (burning, itching or pricking caused by damage to the CNS), affective pain (emotional response), hyperalgesia or nociceptive pain (in response to a noxious stimulus), allodynia (painful response to a stimulus that normally does not cause pain), pain threshold (defined as the last experience of pain witch a subject can recognise).
Based on pain duration: we can differentiate between: acute pain (short term pain well localised), episodic pain (transient from acute pain), chronic pain (constant or intermittent daily pain, persisting for grater that three months, usually after the tissues are expected to have healed), paroxysmal pain (sudden severe pain occurring without warning or injury whose symptoms may last for seconds or minutes).
Based on pathophysiology: nociceptive pain and neuropathic pain. The nociceptive pain is transmitted to a conscious level of awareness after nociceptors are activated. The neuropathic pain originates when the nervous system is damaged by a disease or injury. It can be caused by a lesion in the CNC or in the PNS. It can be propagated by two mechanisms: the generation of ectopic impulses at demyelinated lesions in response to a neural damage, and by interruption of inhibitory impulses from the brain that diminished the threshold that generates pain.
Several pathways have been identified for transmission of nociceptive impulses in the spinal cord: the spinothalamic tract, the spinocervicothalamic tract, the spinoreticular tract, the spinomesencephalic tract. The fascilus gracilis has also been pointed out as a nociceptive pathway. These tracts are shown on the attached images.
The response to a noxious stimulus in an animal may be the turning of the head, attempt to escape or vocalization. The absence or presence of pain is a valuable tool to provide prognostic information. A complete loss of nociception is a clear indicator of an acute or severe injury. On the other hand, the presence of pain can be al helpful localizer of a lesion on palpation.
The pain is a sensation localized in the cerebrum. In this part of the encephalon, the decision that the tissue is in danger and if something has to be done to avoid the damage or to prevent of worsening will be taken. The encephalon may decide to diminish the nociceptive signals that reach the cerebrum in order to accommodate momentarily to the situation. Some specific areas of the encephalon may be activated to send inhibitory signals that reach the pool of neurons on the dorsal horn of the spinal cord in order to block the ascending nociceptive tracts. This is referred as pain inhibition system. Among these structures are the periaqueductual gray matter, the basal nuclei, the septal nuclei and the locus coeruleus.
The periaqueductal gray matter (PAGM) receives afferences from the thalamus, hypothalamus, cerebral cortex, and from the spinothalamic and spinomesencephalic tracts. The PAGM activates to the noradrenergic cells of the medullary reticular formation (MRF) and the serotoninergic cells of the raphe nuclei (RN). Both, the MRF and the RN, excite inhibitory neurons that are localized in the dorsal horn by releasing inhibitory neurotransmitters such as γ-aminobutyric acid (GABA), glycine and enkephalin that inhibit the ascending fibers to the thalamus.
The basal nuclei are also involved in pain processing including the sensory-discriminative, emotional, affective, cognitive dimension and modulatory of pain. The amygdala plays an important role in the emotional evaluation of sensory stimuli, emotional learning, memory, and of affective states. It receives information form all sensory modalities, including nociceptive information, and has access to pain modulatory systems through forebrain and brainstem connections. There is evidence that the amygdala integrates nociceptive information with affective content, contributes to the emotional response to the pain, and serves as a neuronal interface for reciprocal relationship between pain and the negative affect of it.
Other brain nuclei also contribute to control pain. These are the septal nuclei (that produce acetylcholine, noradrenaline and opioid peptides) and the locus coeruleus (that synthesizes, store and releases noradrenaline).
The gate control theory of pain transmission was proposed in 1965 by Melzak and Wall. It consists of neural networks in the dorsal horn that respond to afferent collaterals fibers that enter the spinal cord from the PNS. These nociceptive, myelinated and unmyelinated, collateral fibers synapse on interneurons of the neural networks that release endorphin, and encephalin. These neurotransmitters block the synapsis of the afferents fibers on second order neurons which axons form ascending tracts.
Nociception from blood vessels and nerves
Heart and blood vessels are densely innervated by sensory nerve endings that express chemo-, mechano- and thermo sensitive receptors. The nociceptive impulses control the sympathetically mediated constrictor effect.
All layers of the nerve are innervated and have an important plexus of nociceptors. The majority of these fibers are unmyelinated . They supply sympathetic and nociceptive fibers to the vessels and they originate from the nerve trunk and from the perivascular plexuses.
Nociception from intervertebral disk
The longitudinal ligaments, the anulus fibrosus from the intervertebral disks and intervertebral joints are somatosensory innervated by nerves derived from meningeal rami, and sympathetically innervated from gray communicating rami .
 Franklin, S. in Conn’s Translational Neuroscience. 2017pp. 113-129.
 Dickman, J.D., in Fundamental Neuroscience for Basic and Clinical Applications (Fifth Edition), 2018.
 Sengul, G. and Watson, Ch., in The Human Nervous System (Third Edition), 2012.
 Rea, P., in Essential Clinical Anatomy of the Nervous System, 2015.
 Darby, S.A., Frysztak, R.J., in Clinical Anatomy of the Spine, Spinal Cord, and ANS, Third Edition, 2014.
 Belhaj-saif and Cheney. Plasticity in the distribution of the red nucleus output to forearm muscles after unilateral lesions of the pyramidal tract. J. Neurophysiol. 2000 May; 83 (5): 3147-53.
 These corticonuclear or corticobulbar fibers terminate on motor nuclei of the cranial nerves. This tract has not been clearly stablished in cats.
 In Veterinary neuroanatomy and clinical neurology. Fourth edition. Elsevier. Pag. 516.
 The intention tremor is a dyskinetic disorder that increases on attempted voluntary movement. It increases as an extremity approaches the endpoint of deliberate and visually guided movement. It usually increases by the initiation of voluntary movements.
 The lateral vestibulospinal tract is formed by axons that descend from the lateral vestibular nucleus and travel in the ventral funiculus. It facilitates the ipsilateral extensor muscles. Some fibers cross the midlane at different sites of the white comissure and inhibit the contralateral extensor muscles.
 The medial vestibulospinal tract is formed by axons from the rostral, medial and caudal vestibular nuclei that reach cervical spinal cord segments. The fibers of the medial vestibulospinal tract travel in the medial longitudinal fasciculus in the brain stem, and in the ventral funiculus in the cervical spinal cord.
 Tamur, S., Nakamot, Y., Uemura, T., and Tamura, Y. Head Tilting Elicited by Head Turning in Three Dogs with Hypoplastic Cerebellar Nodulus and Ventral Uvula. Frontiers in Veterinary Science. November 2016 Volume 3 Article 104.
 Grillner, S. Biological pattern generation: the cellular and computational logic of networks in motion. Neuron 52, 751-766.2006.
 Takakusaki, K. Functional neuroanatomy for posture and gait control. J. Mov. Disord. 2017, 10 (1): 1-17.
 Grillner, S, Georgopoulos, AP, Jordan, LM. Selection and initiation of motor behavior. In: Stein PSG, Grillner S, Selverston AI, Stuart DG, editors. Neurons, networks, and motor behavior. Cambridge, MA: The MIT Press, 1997;3- 19. In Takakusaki, K. Functional neuroanatomy for posture and gait control. J. Mov. Disord. 2017, 10 (1): 1-17.
 De Lahunta, A. in Veterinary neuroanatomy and clinical neurology. Fourth edition. Elsevier. Pag. 233.
 Lajoie K, Andujar JE, Pearson K, Drew T. Neurons in area 5 of the posterior parietal cortex in the cat contribute to in- terlimb coordination during visually guided locomotion: a role in working memory. J Neurophysiol 2010;103:2234- 2254. In Takakusaki, K. Functional neuroanatomy for posture and gait control. J. Mov. Disord. 2017, 10 (1): 1-17.
 Büttner U, Glasauer S, Glonti L, Guan Y, Kipiani E, Kleine J, et al. Multimodal signal integration in vestibular neu- rons of the primate fastigial nucleus. Ann N Y Acad Sci 2003;1004:241-251. In Takakusaki, K. Functional neuroanatomy for posture and gait control. J. Mov. Disord. 2017, 10 (1): 1-17.
 From Latin: “suffering, grief”.
 From Latín: noceo, “injure” y capio, “to take”.
 Saper, C.B. and Stornetta, R.L., in The Rat Nervous System (Fourth Edition), 2015. Carrive, P. and Morgan, M.M., in The Human Nervous System (Third Edition), 2012. Westlund,, K.N. and D. WillisJr., W., in The Human Nervous System (Third Edition), 2012. McCrimmon, D.R., et al. , in Encyclopedia of Neuroscience,2009. Puelles, L., et al., in The Mouse Nervous System, 2012. Novak, P. , in Neurobiology of Disease, 2007. Johns, P. And Path, F.R.C., in Clinical Neuroscience, 2014. Ashwell, K.W.S. and Mai, J.K., in The Human Nervous System (Third Edition), 2012.
 Borsook et al. A key role of the basal ganglia in pain and analgesia - insights gained through human functional imaging. Molecular Pain. 2010, 6:27.
 Neugebauer, V. Amygdala—Pain Processing and Pain Modulation V. Molecular Pain pp 265-279.
 Nathan, P.W.and Rudge, P. Testing the gate-control theory of pain in man. The Journal of Neurology, Neurosurgery and Psychiatry, 1974, 37, 1366-1372. Ropero Peláez, F.J. and Taniguchi, S. Research Article The Gate Theory of Pain Revisited: Modeling Different Pain Conditions with a Parsimonious Neurocomputational Model. Neural Plasticity. Volume 2016, Article ID 4131395, 14 pages. The gate control theory of pain. Br. Med. J. 1978 Aug 26; 2(6137): 586–587. Melzak, R. Gate control theory: On the evolution of pain concepts. Pain Forum, Vol. 5, Issue 2 Pag: 93-156. Moayedi, M. And Davis, K.D. Theories of pain: from specific to gait control.. J. Neurophysiology 109: 5-12. 2013.
 Premkumar, L.S and Raisinghani, M. Nociceptors in cardiovascular functions: complex interplay as a result of cyclooxygenase inhibition. Molecular Pain 2006, 2:26. 17 August 2006.
 Thomas, G.D. Neural control of the circulation. Adv Physiol Educ 35: 28–32, 2011.
 Bove, G. Epi-Perineurial Anatomy, Innervation, and Axonal Nociceptive Mechanisms. J. Bodyw Mov Ther. 2008 July ; 12(3): 185–190.
 Hromada J. On the nerve supply of the connective tissue of some peripheral nervous tissue system components. Acta Anatomica 1963;55:343–35.
 Reina et al.Morfología de los nervios periféricos, de sus cubiertas y de su vascularización. Rev. Esp. Anestesiol. Reanim. 2000; 47: 464-475.
 N. Bogduk, Wendy Tynan and A. S. Wilson. The nerve supply to the human lumbar intervertebral disc. J.Anat. (1981), 132, 1, pp. 39-56
 García-Cosamalón, J., del Valle, Miguel E. Marta G. Calavia, García-Suárez, .O, López-Muñiz, Alfonso, Otero, J. and Vega, J. A. Intervertebral disc, sensory nerves and neurotrophins: who is who in discogenic pain? J.Anat. (2010), 217, pp. 1-15