книги студ / color atlas of physiology 5th ed[1]. (a. despopoulos et al, thieme 2003)

Nociception and Pain

(desensitization) and stimulated by prostaglandin E2 or bradykinin, which is released in response to inflammation (sensitization; !A). Endogenous opioids (e.g., dynorphin, enkephalin, endorphin) and exogenous opioids (e.g., morphium) as well as inhibitors of prostaglandin synthesis (!p. 269) are therefore able to alleviate pain (analgesic action).

Inflammatory sensitization (e.g., sunburn) lowers the threshold for noxious stimuli, leading to excessive

318sensitivity (hyperalgesia) and additional pain resulting from non-noxious stimuli to the skin (allody-

nia), e.g., touch or warm water (37 #C). Once the

nocisensors are stimulated, they start to release neuropeptides such as substance P or CGRP (calcitonin gene-related peptide) that cause inflammation of the surrounding vessels (neurogenic inflammation).

Projected pain. Damage to nociceptive fibers causes pain (neurogenic or neuropathic) that is often projected to and perceived as arising from the periphery. A prolapsed disk compressing a spinal nerve can, for example, cause leg pain. Nociceptive fibers can be blocked by cold or local anesthesia.

Nociceptive tracts (!C1). The central axons of nociceptive somatic neurons and nociceptive afferents of internal organs end on neurons of the dorsal horn of the spinal cord. In many cases, they terminate on the same neurons as the skin afferents.

Referred pain (!B). Convergence of somatic and visceral nociceptive afferents is probably the main cause of referred pain. In this type of pain, noxious visceral stimuli cause a perception of pain in certain skin areas called Head’s zones. That for the heart, for example, is located mainly in the chest region. Myocardial ischemia is therefore perceived as pain on the surface of the chest wall (angina pectoris) and often also in the lower arm and upper abdominal region.

In the spinal cord, the neuroceptive afferents cross to the opposite side (decussation) and are conducted in the tracts of the anterolateral funiculus—mainly in the spinothalamic tract— and continue centrally via the brain stem where they join nociceptive afferents from the head (mainly trigeminal nerve) to the thalamus (!C1). From the ventrolateral thalamus, sensory aspects of pain are projected to S1 and S2 areas of the cortex. Tracts from the medial thalamic nuclei project to the limbic system and other centers.

Components of pain. Pain has a sensory component including the conscious perception of site, duration and intensity of pain; a motor component (e.g., defensive posture and withdrawal reflex; !p. 320), an autonomic component (e.g., tachycardia), and an affective component (e.g., aversion). In addition, pain assessments based on the memory of a previous pain experience can lead to pain-related behavior (e.g., moaning).

In the thalamus and spinal cord, nociception can be inhibited via descending tracts with the aid of various transmitters (mainly opioids). The nuclei of these tracts (!C2, blue) are located in the brain stem and are mainly activated via the nociceptive spinoreticular tract (negative feedback loop).

Plate 12.5 Nociception and Pain

319

Polysynaptic Reflexes

Unlike monosynaptic stretch reflexes, polysynaptic reflexes occur through the co-activa- tion of α and γ motoneurons (!p. 316). The reflex excitability of α motoneurons is largely controlled by supraspinal centers via multiple interneurons (!p. 324). The brain can therefore shorten the reflex time of spinal cord reflexes when a noxious stimulus is anticipated.

Supraspinal lesions or interruption of descending tracts (e.g., in paraplegics) can lead to exaggeration of reflexes (hyperreflexia) and stereotypic reflexes. The absence of reflexes (areflexia) corresponds to specific disorders of the spinal cord or peripheral nerve.

Synaptic Inhibition

GABA (γ-aminobutyric acid) and glycine (!p. 55f.) function as inhibitory transmitters in the spinal cord. Presynaptic inhibition (!B) occurs frequently in the CNS, for example, at synapses between type Ia afferents and α motoneurons, and involves axoaxonic synapses of GABAergic interneurons at presynaptic nerve endings. GABA exerts inhibitory effects at the nerve endings by increasing the membrane conductance to Cl– (GABAA receptors) and K+ (GABAB receptors) and by decreasing the conductance to Ca2+ (GABAB receptors). This decreases the release of transmitters from the nerve ending of the target neuron (!B2), thereby lowering the amplitude of its postsynaptic EPSP (!p. 50). The purpose of presynaptic inhibition is to reduce certain influences on the motoneuron without reducing the overall excitability of the cell.

In postsynaptic inhibition (!C), an inhibitory interneuron increases the membrane conductance of the postsynaptic neuron to Cl– or K+, especially near the axon hillock, thereby short-circuiting the depolarizing electrical currents from excitatory EPSPs (!p. 54 D).

The interneuron responsible for postsynaptic inhibition is either activated by feedback from axonal collaterals of the target neurons (recurrent inhibition of motoneurons via glycinergic Renshaw cells; !C1) or is directly activated by another neuron via feed-forward control (!C2). Inhibition of the ipsilateral extensor (!A2, A3) in the flexor reflex is an example of feed-forward inhibition.

12 Central Nervous System and Senses

322

Motor System

The motor cortex consists of three main areas (!C, top; !see p. 311 E for area numbers):

(a) primary motor area, M1 (area 4), (b) premotor area, PMA (lateral area 6); and (c) supplementary motor area, SMA (medial area 6). The motor areas of the cortex exhibit somatotopic organization with respect to the target

324muscles of their fibers (shown for M1 in B) and their mutual connections.

Cortical afferents. The cortex receives motor input from (a) the body periphery (via thalamus ! S1 [!p. 323 A] ! sensory association cortex ! PMA); (b) the basal ganglia (via thalamus ! M1, PMA, SMA [!A2] ! prefrontal association cortex); (c) the cerebellum (via thalamus ! M1, PMA; !A2); and (d) sensory and posterior parietal areas of the cortex (areas 1–3 and 5–7, respectively).

Cortical efferents. (!C, D, E, F) Motor output from the cortex is mainly projected to (a) the spinal cord, (b) subcortical motor centers (see below and p. 328), and (c) the contralateral cortex via commissural pathways.

The pyramidal tract includes the corticospinal tract and part of the corticobulbar tract. Over 90% of the pyramidal tract consists of thin fibers, but little is known about their function. The thick, rapidly conducting corticospinal tract (!C) project to the spinal cord from areas 4 and 6 and from areas 1–3 of the sensory cortex. Some of the fibers connect monosynaptically to α and γ motoneurons responsible for finger movement (precision grasping). The majority synapse with interneurons of the spinal cord, where they influence input from peripheral afferents as well as motor output (via Renshaw’s cells) and thereby spinal reflexes.

Function of the Basal Ganglia

Circuitry. The basal ganglia are part of multiple parallel corticocortical signal loops. Associative loops arising in the frontal and limbic cortex play a role in mental activities such as assessment of sensory information, adaptation of behavior to emotional context, motivation, and long-term action planning. The function of the skeletomotor and oculomotor loops

(see below) is to coordinate and control the velocity of movement sequences. Efferent projections of the basal ganglia control thalamocortical signal conduction by (a) attenuating the inhibition (disinhibiting effect, direct mode) of the thalamic motor nuclei and the superior colliculus, respectively, or (b) by intensifying their inhibition (indirect mode).

The principal input to the basal ganglia comes from the putamen and caudate nucleus, which are collectively referred to as the striatum. Neurons of the striatum are activated by

!

A.Events from decision to move to execution of movement

C. Descending motor tracts

Photo: M. Jeannerod

Tongue

Throat

325

12 Central Nervous System and Senses

326

!

tracts from the entire cortex and use glutamate as their transmitter (!D). Once activated, neurons of the striatum release an inhibitory transmitter (GABA) and a co-transmitter— either substance P (SP) or enkephalin (Enk.,

!D; !p. 55). The principal output of the basal ganglia runs through the pars reticularis of the substantia nigra (SNr) and the pars interna of the globus pallidus (GPi), both of which are inhibited by SP/GABAergic neurons of the striatum (!D).

Both SNr and GPi inhibit (by GABA) the ventrolateral thalamus with a high level of spontaneous activity. Activation of the striatum therefore leads to disinhibition of the thalamus by this direct pathway. If, however, enkephalin/GABA-releasing neurons of the striatum are activated, then they inhibit the pars externa of the globus pallidus (GPe) which, in turn, inhibits (by GABA) the subthalamic nucleus. The subthalamic nucleus induces glutamatergic activation of SNr and GPi. The ultimate effect of this indirect pathway is increased thalamic inhibition. Since the thalamus projects to motor and prefrontal cortex, a corticothalamocortical loop that influences skeletal muscle movement (skeletomotor loop) via the putamen runs through the basal ganglia. An oculomotor loop projects through the caudate nucleus, pars reticularis and superior colliculus and is involved in the control of eye movement (!pp. 342, 360). Descending tracts from the SNr project to the tectum and nucleus pedunculus pontinus.

The fact that the pars compacta of the substantia nigra (SNc) showers the entire striatum with dopamine (dopaminergic neurons) is of pathophysiological importance (!D). On the one hand, dopamine binds to D1 receptors (rising cAMP levels), thereby activating SP/GABAergic neurons of the striatum; this is the direct route (see above). On the other hand, dopamine also reacts with D2 receptors (decreasing cAMP levels), thereby inhibiting enkephalin/GABAergic neurons; this is the indirect route. These effects of dopamine are essential for normal striatum function. Degeneration of more than 70% of the dopaminergic neurons of the pars compacta results in excessive inhibition of the motor areas of the thalamus, thereby impairing voluntary motor function. This occurs in Parkinson’s disease and can be due genetic predisposition, trauma (e.g., boxing), cerebral infection and other causes. The characteristic symptoms of disease include poverty of movement (akinesia), slowness of movement (bradykinesia), a festinating gait, small handwriting (micrography), masklike facial expression, muscular hypertonia (rigor), bent posture, and a tremor of resting muscles (“money-counting” movement of thumb and fingers).

Function of the Cerebellum

The cerebellum contains as many neurons as the rest of the brain combined. It is an important control center for motor function that has afferent and efferent connections to the cortex and periphery (!F, top panel). The cerebellum is involved in the planning, execution and control of movement and is responsible for motor adaptation to new movement sequences (motor learning). It is also cooperates with higher centers to control attention, etc.

Anatomy (!F, top). The archeocerebellum (flocculonodular lobe) and paleocerebellum (pyramids, uvula, paraflocculus and parts of the anterior lobe) are the phylogenetically older parts of the cerebellum. These structures and the pars intermedia form the median cerebellum. The neocerebellum (posterior lobe of the body of the cerebellum) is the phylogenetically younger part of the cerebellum and forms the lateral cerebellum. Based on the origin of their principal efferents, the archicerebellum and vermis are sometimes referred to as the vestibulocerebellum, the paleocerebellum as the spinocerebellum, and the neocerebellum as the pontocerebellum. The cerebellar cortex is the folded (fissured) superficial gray matter of the cerebellum consisting of an outer molecular layer of Purkinje cell dendrites and their afferents, a middle layer of Purkinje cells (Purkinje somata), and an inner layer of granular cells. The outer surface of the cerebellum exhibits small, parallel convolutions called folia.

The median cerebellum and pars intermedia of the cerebellum mainly control postural and supportive motor function (!F1,2) and oculomotor function (!pp. 342 and 360). Input: The median cerebellum receives afference copies of spinal, vestibular and ocular origin and efference copies of descending motor signals to the skeletal muscles. Output from the median cerebellum flows through the intracerebellar fastigial, globose, and emboliform nuclei to motor centers of the spinal cord and brain stem and to extracerebellar vestibular nuclei (mainly Deiter’s nucleus). These centers control oculomotor function and influence locomotor and postural/supportive motor function via the vestibulospinal tract.

The lateral cerebellum (hemispheres) mainly takes part in programmed movement (!F3), but its plasticity also permits motor adaptation and the learning of motor sequences. The hemispheres have two-way

!

D.Basal ganglia: afferent and efferent tracts

Efferents of motor cortex

Motor thalamus

Inhibition Excitation

(In parts after Delong)

E.Centers, tracts and afferents for postural motor function

Motor cortex

Cerebellum Basal

ganglia

Vestibular

nuclei Medulla oblongata

Lateral vestibulospinal tract

Activation Inhibition Inhibition Activation

Flexors Extensors

Plate 12.9 Motor System II

327