Depolarization Steps: 1) Negative charge inside of membrane (due to K ions) positive charge on outside (Na), more negative than positive. 2) Action potential causes the sodium channels to open and Na ions flow into inner membrane; K+ ions flow out. 3) Sodium-potassium pump depolarize cell during refractory period; 2:3 Na:K pumped into cell Actions potential do not vary but the rate/ number of neuron stimulated will result in high-intensity stimulation Axons covered by myelin sheath= insulation/ protective Nodes of Ranvier: section of axon where myelin sheath are not present or absent. Impulses hope along these nodes to get better conductivity and speed. Synapse: connection between neurons (axons and dendrites) Neurotransmission occurs between axon and dendrites in synaptic cleft 5 steps Synthesis- chemicals have made within the neuron Storage- these chemicals are stored within the synaptic vesicles Release- chemicals move across the synaptic cleft from presynaptic neuron (axon) to post synaptic neuron (dendrites) Binding: the vesicle bind to the receptor sites on the neurons. These chemicals will (a) depolarize the neuron by exciting it or (b) hyperpolarize the neuron and inhibit it. Deactivation: shuts off, is depolarized
Exciting Chemicals: Glutamate, Acetylcholine, Norepinephrine, Dopamine Inhibiting Chemicals: GABA, Serotonin, Dopamine Acetylcholine -&gt; (motor movement, sleep, dreaming, muscle) Alzheimer’s disease (lack of) Botulism: blocked Ach, paralysis Dopamine -&gt; Parkinson’s disease (lack of) can be treated; also treats schizophrenia (overload)/ delusions Serotonin (5HT) -&gt; sensitivity to it linked to depression (due to undersupply of it) Endorphins -&gt; reduce pain Neuromodulators -&gt; widespread effect Drugs can mimic some neurotransmitters (block uptake, bind at stop TP) Sensory Neurons: sent info the brain/ spine Motor Neurons: send impulses from brain/ spine to muscles/ organs Interneurons: connective neurons
Somatic Nervous system: voluntary movements (muscles, senses) Autonomic Nervous system: controls glands, heart, etc. Fight-or-Flight: Sympathetic: arousal to stress Parasympathetic: recovery from stress [HOMOEOSTATIS]
Spinal Circuitry and Ascending Neural Pathways On entry into the spinal cord, the central axons of the somatosensory neurons branch extensively and project to nuclei in the spinal gray matter. Some branches become involved in local spinal cord reflexes and directly initiate motor reflexes (e.g., flexor-withdrawal reflex). Two parallel pathways, the rapid conducting discriminative pathway and the slower conducting anterolateral pathway, transmit information from the spinal cord to the thalamic level of sensation, each taking a different route through the CNS. The Discriminative Pathway. The discriminative pathway, which crosses at the base of the medulla, is used for the rapid transmission of sensory information such as discriminative touch. It contains branches of primary afferent axons that travel up the ipsilateral (i.e., same side) dorsal columns of the spinal cord white matter and synapse with highly evolved somatosensory input association neurons in the medulla. The discriminative pathway uses only three neurons to transmit information from a sensory receptor to the somatosensory strip of parietal cerebral cortex of the opposite side of the brain: (1) the primary dorsal root ganglion neuron, which projects its central axon to the dorsal column nuclei; (2) the dorsal column neuron, which sends its axon through a rapid conducting tract, called the medial lemniscus, that crosses at the base of the medulla and travels to the thalamus on the opposite side of the brain, where basic sensation begins; and (3) the thalamic neuron, which projects its axons through the somatosensory radiation to the primary sensory cortex. The medial lemniscus is joined by fibers from the sensory nucleus of the trigeminal nerve (cranial nerve V) that supplies the face. Sensory information arriving at the sensory cortex by this route can be discretely localized and discriminated in terms of intensity. One of the distinct features of the discriminative pathway is that it relays precise information regarding spatial orientation. This is the only pathway taken by the sensations of muscle and joint movement, vibration, and delicate discriminative touch, as is required to differentiate correctly the location of touch on the skin at two neighboring points (i.e., two-point discrimination). One of the important functions of the discriminative pathway is to integrate the input from multiple receptors. The sense of shape and size of an object in the absence of visualization, called stereognosis, is based on precise afferent information from muscle, tendon, and joint receptors. For example, a screwdriver is perceived as being different from a knife in terms of its texture (tactile sensibility) and shape based on the relative position of the fingers as they move over the object. This complex interpretive perception requires that the discriminative system must be functioning optimally and that higherorder parietal association cortex processing and prior learning must have occurred. If the discriminative somatosensory pathway is functional but the parietal association cortex has become discretely damaged, the person can correctly describe the object but does not recognize that it is a screwdriver. This deficit is called astereognosis. The Anterolateral Pathway. The anterolateral pathways (anterior and lateral spinothalamic pathways), which crosses within the first few segments of entering the spinal cord, consists of bilateral multisynaptic slow-conducting tracts. These pathways provide for transmission of sensory information such as pain, thermal sensations, crude touch, and pressure that does not require discrete localization of signal source or fine discrimination of intensity. The fibers of the anterolateral pathway originate in the dorsal horns at the level of the segmental nerve, where the dorsal root neurons enter the spinal cord. They cross in the anterior commissure of the cord, within a few segments of origin, to the opposite anterolateral pathway, where they ascend upward toward the brain. The spinothalamic tract fibers synapse with several nuclei in the thalamus, but en route they give off numerous branches that travel to the reticular activating system of the brain stem. These projections provide the basis for increased wakefulness or awareness after strong somatosensory stimulation and for the generalized startle reaction that occurs with sudden and intense stimuli. They also stimulate autonomic nervous system responses, such as an increase in blood pressure and heart rate, dilation of the pupils, and the pale, moist skin that results from constriction of the cutaneous blood vessels and activation of the sweat glands. There are two subdivisions in the anterolateral pathway: the outer neospinothalamic tract and the inner paleospinothalamic tract. The neospinothalamic tract, which carries bright pain, consists of a sequence of at least three neurons with long axons. It provides for relatively rapid transmission of sensory information to the thalamus. The paleospinothalamic tract, which is phylogenetically older than the neospinothalamic system, consists of bilateral, multisynaptic slowconducting tracts that transmit sensory signals that do not require discrete localization of signal source or discrimination of fine gradations in intensity. This slower-conducting pathway also projects into the intralaminar nuclei of the thalamus, which have close connections with the limbic cortical systems. This circuitry provides touch with its affective or emotional aspects.
Classical and non-classical views of pain transmission and pain modulation (a). Classical pain transmission pathway. When a noxious (painful) stimulus is encountered, such as stepping on a nail as shown, peripheral “pain”-responsive A-delta and C nerve fibers are excited. These axons relay action potentials to the spinal cord dorsal horn. Here, neurotransmitters are released by the sensory neuron and these chemicals bind to and activate postsynaptic receptors on pain transmission neurons (PTNs) whose cell bodies reside in the dorsal horn. Axons of the PTNs then ascend to the brain, carrying information about the noxious event to higher centers. The synapse interconnecting the peripheral sensory neuron and the dorsal horn PTN is shown in detail in (b) and (c). (b): Normal pain. Under basal conditions, pain is not modulated by glia. Under these circumstances, glia are quiescent, and thus not releasing pain modulatory levels of neuroexcitatory substances. Information about noxious stimuli arrives from the periphery along A-delta and C fibers, causing the release of substance P and excitatory amino acids (EAAs) in amounts appropriate to the intensity and duration of the initiating noxious stimulus. Activation of neurokinin-1 (NK-1) receptors by substance P and activation of AMPA receptors by EAAs cause transient depolarization of the PTNs, thereby generating action potentials that are relayed to brain. NMDA-linked channels are silent as they are chronically “plugged” by magnesium ions. (c) Pain facilitation: classical view. In response to intense and/or prolonged barrages of incoming “pain” signals, the PTNs become sensitized and over-respond to subsequent incoming signals The intense and/or prolonged barrage depolarizes the PTNs such that the magnesium ions exit the NMDA-linked channel. The resultant influx of calcium ion activates constitutively expressed nitric oxide synthase (cNOS), causing conversion of L-arginine to nitric oxide (NO). Because it is a gas, NO rapidly diffuses out of the PTNs. This NO acts presynaptically to cause exaggerated release of substance P and EAAs. Postsynaptically, NO causes the PTNs to become hyperexcitable. Glia have not been considered to have a role in creating pain facilitation in this neuronally driven model. (d): Pain facilitation: new view. Here, glial activation is conceptualized as a driving force for creating and maintaining pain facilitation. The role of glia is superimposed on the NMDA-NO-driven neuronal changes detailed in (c), so only the aspects added by including glia in the model are described here. Glia are activated (shown as hypertrophied relative to (b), as this reflects the remarkable anatomical changes that these cells undergo on activation) by three sources: bacteria and viruses which bind specific activation receptors expressed by microglia and astrocytes; substance P, EAAs, fractalkine, and ATP released by A-delta and/or C fiber presynaptic terminals (shown here) or by brain-to-spinal cord pain enhancement pathways (not shown); and NO, prostaglandins (PGs) and fractalkine released from PTNs. Following activation, microglia and astrocytes cause PTN hyperexcitability and the exaggerated release of substance P and EAAs from presynaptic terminals. These changes are created by the glial release of NO, EAAs, reactive oxygen species (ROS), PGs, proinflammatory cytokines (for example, IL1, IL6 or TNF), and nerve growth factor. Modified by Journal of Internal Medicine with permission, from Trends in Neuroscience.
Both theories focus on the neurophysiologic basis of pain, and both probably apply. Specific nociceptive afferents have been identified; however, almost all afferent stimuli, if driven at a very high frequency, can be experienced as painful.
Primary pain pathways. The transmission of incoming nociceptive impulses is modulated by dorsal horn circuitry that receives input from peripheral touch receptors and from descending pathways that involve the limbic cortical systems (orbital frontal cortex, amygdala, and hypothalamus), periaqueductal endogenous analgesic center in the midbrain, pontine noradrenergic neurons, and the nucleus raphe magnus (NRM) in the medulla. Dashed lines indicate inhibition or modulation.
Evaluates pain threshold. Standardized (1.52cm2) flat circular probe is pushed against subject’s skin until pain threshold is reached. (lbs. and kgs).
Analgesia is the absence of pain on noxious stimulation or the relief of pain without loss of consciousness. The inability to sense pain may result in trauma, infection, and even loss of a body part or parts. Inherited insensitivity to pain may take the form of congenital indifference or congenital insensitivity to pain. In the former, transmission of nerve impulses appears normal, but the appreciation of painful stimuli at higher levels appears to be absent. In the latter, a peripheral nerve defect apparently exists such that transmission of painful nerve impulses does not result in perception of pain. Whatever the cause, persons who lack the ability to perceive pain are at constant risk of tissue damage because pain is not serving its protective function. Myofascial trigger points are foci of exquisite tenderness found in many muscles and can be responsible for pain projected to sites remote from the points of tenderness. Trigger points are widely distributed in the back of the head and neck and in the lumbar and thoracic regions. These trigger points cause reproducible myofascial pain syndromes in specific muscles. These pain syndromes are the major source of pain in clients at chronic pain treatment centers.
In the acute infection, proportionately more of the large nerve fibers are destroyed. Regenerated fibers appear to have smaller diameters. Because there is a relative loss of large fibers with age, elderly persons are particularly prone to suffering because of the shift in the proportion of large- to small-diameter nerve fibers. Older patients have pain, dysesthesia, and hyperesthesia after the acute phase; these are increased by minor stimuli. Early treatment of shingles with high doses of systemic corticosteroids and an oral antiviral drug such as acyclovir or valacyclovir, a medication that inhibits herpesvirus DNA replication, may reduce the incidence of postherpetic neuralgia. Initially, postherpetic neuralgia can be treated with a topical anesthetic agent. A tricyclic antidepressant medication may be used for pain relief. Regional nerve blockade (i.e., stellate ganglion, epidural, local infiltration, or peripheral nerve block) has been used with limited success.
The disease typically follows a progressive course, with a mean survival period of 2 to 5 years from the onset of symptoms. ALS affects motoneurons in three locations: the anterior horn cells of the spinal cord; the motor nuclei of the brain stem, particularly the hypoglossal nuclei; and the UMNs of the cerebral cortex. The fact that the disease is more extensive in the distal, rather than the proximal, parts of the affected tracts in the lower spinal cord suggests that affected neurons first undergo degeneration at their distal terminals and that the diseasem proceeds in a centripetal direction until ultimately the parent nerve cell dies. A remarkable feature of the disease is that the entire sensory system, the regulatory mechanisms of control and coordination of movement, and the intellect remain intact. The neurons for eye movement and the parasympathetic neurons in the sacral spinal cord also are spared. Degeneration and loss of neurons in the primary motor cortex leads to loss of fibers within the corticospinal tract and lateral and anterior columns of the spinal cord.6 It is this fiber atrophy, called amyotrophy, that appears in the name of the disease. The loss of nerve fibers in lateral columns of the white matter of the spinal cord along with fibrillary gliosis imparts a firmness or sclerosis to this CNS tissue; the term lateral sclerosis designates these changes. The cause of LMN and UMN destruction in ALS is uncertain. Five percent to 10% of cases are familial; the others are believed to be sporadic, with no family history of the disease. Recently, mutations to a gene encoding superoxide dismutase 1 (SOD1) was mapped to chromosome. This enzyme functions in the prevention of free radical formation. The mutation accounts for 20% of familial ALS, with the remaining 80% being caused by mutations in other genes. Five percent of persons with sporadic ALS also have SOD1 mutations. Possible targets of SOD1-induced toxicity include the neurofilament proteins, which function in the axonal transport of molecules necessary for the maintenance of axons. Another suggested mechanism of pathogenesis in ALS is exotoxic injury through activation of glutamate-gated ion channels, which are distinguished by their sensitivity to N-methyl-D-aspartic acid. The possibility of glutamate excitotoxicity in the pathogenesis of ALS was suggested by the finding of increased glutamine levels in the cerebrospinal fluid of patients with sporadic ALS. Although autoimmunity has been suggested as a cause of ALS, the disease does not respond to the immunosuppressant agents that normally are used in treatment of autoimmune disorders.
The prevalence of MS varies considerably around the world. The disease is more prevalent in the colder northern latitudes; it is more common in the northern Atlantic states, the Great Lakes region, and the Pacific Northwest than in the southern parts of the United States. Other high-incidence areas include northern Europe, Great Britain, southern Australia, and New Zealand. The incidence among women is almost double that of men. Although MS is not directly inherited, there is a familial predisposition in some cases, suggesting a genetic influence on susceptibility. For example, there is evidence of a genetic linkage of MS susceptibility to the inherited major histocompatibility complex DR2 haplotype. The pathophysiology of MS involves the demyelination of nerve fibers in the white matter of the brain, spinal cord, and optic nerve. In the CNS, myelin is formed by the oligodendrocytes, chiefly those lying among the nerve fibers in the white matter. The properties of the myelin sheath—high electrical resistance and low capacitance—permit it to function as an electrical insulator. Demyelinated nerve fibers display a variety of conduction abnormalities, ranging from decreased conduction velocity to conduction blocks. The lesions of MS consist of hard, sharp-edged demyelinated or sclerotic patches that are macroscopically visible throughout the white matter of the CNS. These lesions, which represent the end result of acute myelin breakdown, are called plaques. The lesions have a predilection for the optic nerves, periventricular white matter, brain stem, cerebellum, and spinal cord white matter. In an active plaque, there is evidence of ongoing myelin breakdown. The sequence of myelin breakdown is not well understood, although it is known that the lesions contain small amounts of myelin basic proteins and increased amounts of proteolytic enzymes, macrophages, lymphocytes, and plasma cells. Oligodendrocytes are decreased in number and may be absent, especially in older lesions. Acute, subacute, and chronic lesions often are seen at multiple sites throughout the CNS. The lesions of MS are generally thought to result from an immune-mediated inflammatory response that occurs in genetically susceptible individuals. The demyelination process in MS is marked by prominent lymphocytic invasion in the lesion. The infiltrate in plaques contains both CD8+ and CD4+ T cells as well as macrophages. Both macrophages and cytotoxic CD8+ T cells are thought to induce oligodendrocyte injury. There also is evidence of antibody-mediated damage involving myelin oligodendroglial protein. Magnetic resonance imaging has shown that the lesions of MS may occur in two stages: a first stage that involves the sequential development of small inflammatory lesions, and a second stage during which the lesions extend and consolidate and when demyelination and gliosis (scar formation) occur. It is not known whether the inflammatory process, present during the first stage, is directed against the myelin or against the oligodendrocytes that produce myelin. There is evidence that remyelination can occur in the CNS if the process that initiated the demyelination is halted before the oligodendrocyte dies
Huntington&apos;s disease is inherited as an autosomal dominant disorder. When disease onset occurs later in life, patients develop involuntary, rapid, jerky movements (chorea) and slow writhing movements of the proximal limbs and trunk (athetosis). When disease onset occurs earlier in life, patients develop signs of parkinsonism with tremor (cogwheeling) and stiffness. The spiny GABAergic neurons of the striatum preferentially degenerate, resulting in a net decrease in GABAergic output from the striatum. This contributes to the development of chorea and athetosis. Dopamine antagonists, which block inhibition of remaining striatal neurons by dopaminergic striatal fibers, reduce the involuntary movements. Neurons in deep layers of the cerebral cortex also degenerate early in the disease, and later this extends to other brain regions, including the hippocampus and hypothalamus. Thus, the disease is characterized by cognitive defects and psychiatric disturbances in addition to the movement disorder. The gene for the disease is located on chromosome 4p and encodes for a 3144-amino acid protein, huntingtin, which is widely expressed and interacts with several proteins involved in intracellular trafficking and endocytosis, gene transcription, and intracellular signaling. The protein contains a trinucleotide (CAG) repeat of 11–34 copies that encodes a polyglutamine domain and is expanded in patients with the disease. Deletion of the gene in mice causes embryonic death, whereas heterozygous animals are healthy. Transgenic mice with an expanded repeat develop a neurodegenerative disorder, suggesting that the disease results from the toxic effect of a gain of function mutation. The mechanisms by which mutant huntingtin causes disease are not certain. The mutant protein is degraded, and the resulting fragments that contain the glutamine repeats form aggregates, which are deposited in nuclear and cytoplasmic inclusions. These fragments may bind abnormally to other proteins and interfere with normal protein processing or disrupt mitochondrial function. Nuclear fragments may interfere with nuclear functions such as gene expression. For example, in the cerebral cortex, mutant huntingtin reduces the production of brain-derived neurotrophic factor by suppressing its transcription. In addition, normal huntingtin is protective for cortical and striatal neurons and blocks the processing of procaspase 9, thereby reducing apoptosis (programmed cell death). Therefore, both loss of neurotrophic support and enhanced caspase activity could promote striatal cell loss in Huntington&apos;s disease.
Alterations in Eye Movements In a fully conscious person, the steady gaze of the eyes at rest results from an intact cerebral cortex exerting control over the brainstem. With brain injury that involves loss of cortical function, the eyes typically rove and move together toward or away from the side of the brain injured, depending on the type of injury. Loss of higher brain centers results in reflexive eye movements, called doll&apos;s head movements. A doll&apos;s head movement is that which occurs when the eyes stare forward, always following the position of the head. Normally, when an individual&apos;s head is passively turned to one side, the eyes move to face the previous, forward direction. With injury to the brainstem, loss of ocular movement occurs, and the eyes become fixed in a direct forward position. A skewed deviation, with one eye looking up and one down, suggests a compressive injury to the brainstem. Normal involuntary cyclic movements of the eyeball (nystagmus responses) in response to ice water delivered into the ear are lost with cortical and brainstem dysfunction.
Pathophysiology of cns
Pathophysiology of thePathophysiology of the
nervous system: violation ofnervous system: violation of
sensory, motor and trophicsensory, motor and trophic
Actuality of the lectureActuality of the lecture
The nervous system as a main regulatory system of an organism in this orThe nervous system as a main regulatory system of an organism in this or
that measure participates in pathogenesis of each diseases. The earliest andthat measure participates in pathogenesis of each diseases. The earliest and
obligatory form of participation of the nervous system in pathology isobligatory form of participation of the nervous system in pathology is
defensive and adaptive the response. The protective reflexes (cough,defensive and adaptive the response. The protective reflexes (cough,
vomiting), protective inhibition, response hypotalamo-hypophysial-adrenalvomiting), protective inhibition, response hypotalamo-hypophysial-adrenal
system belong to such responses.system belong to such responses.
At the same time during development of diseases the nervous systemAt the same time during development of diseases the nervous system
becomes the object of a defeat itself. It is defensive and adaptive thebecomes the object of a defeat itself. It is defensive and adaptive the
response of the damaged nervous system are reduced, and it becomes aresponse of the damaged nervous system are reduced, and it becomes a
source of pathological, harmful to an organism reflexes. Itself graving andsource of pathological, harmful to an organism reflexes. Itself graving and
character of violations of nervous activity depend on localization ofcharacter of violations of nervous activity depend on localization of
pathological process and appear as a complex of diverse symptoms.pathological process and appear as a complex of diverse symptoms.
Frequently there is a pain, which on the essence is typical pathologicalFrequently there is a pain, which on the essence is typical pathological
process, but at the same time has signal and adaptive significance. Theprocess, but at the same time has signal and adaptive significance. The
disturbance of nervous activity is always reflected in the function of internaldisturbance of nervous activity is always reflected in the function of internal
The fundamental knowledges of the reasons and mechanisms of disordersThe fundamental knowledges of the reasons and mechanisms of disorders
motor, sensitive and trophic functions of the nervous system are necessary formotor, sensitive and trophic functions of the nervous system are necessary for
understanding of pathogenesis nervous diseases, and also many symptomsunderstanding of pathogenesis nervous diseases, and also many symptoms
of a damage of internal organs.of a damage of internal organs.
• Nervous System: NeuronsNervous System: Neurons
• Division of the Nervous SystemDivision of the Nervous System
• Pain: features of pain as a kind of sensitivity.Pain: features of pain as a kind of sensitivity.
Etiology and pathogenesis of pain.Etiology and pathogenesis of pain.
• Antinociceptive systemsAntinociceptive systems
• Upper Motor NeuronsUpper Motor Neurons and Disordersand Disorders
• Sensory LossSensory Loss
• Spinal Cord InjuriesSpinal Cord Injuries
• Diseases of the Basal GangliaDiseases of the Basal Ganglia
A). Non nervousA). Non nervous or glial cellsor glial cells..
1). Astrocytes1). Astrocytes
2). Microglia2). Microglia
3). Ependymal3). Ependymal
4). Oliodendrocytes4). Oliodendrocytes
5). Satellite cells5). Satellite cells
6).6). Schwann cellsSchwann cells form myelin sheathsform myelin sheaths
Types of cellsTypes of cells
Types ofTypes of
cellscellsB). NeuronsB). Neurons
1). Structure1). Structure
II).). cell bodycell body oror somasoma -- endoplasmicendoplasmic
reticulum called thereticulum called the nissl bodynissl body..
IIII).). ProcessesProcesses oror tracts (nerves)tracts (nerves)
a).a). Dendrites:Dendrites: input regioninput region
b).b). Axon:Axon: Carries information awayCarries information away
c).c). Synaptic knobsSynaptic knobs oror AxonalAxonal
a).a). myelin sheathmyelin sheath -- protects andprotects and
electrically insulates fibers conductelectrically insulates fibers conduct
nerve impulses faster thannerve impulses faster than
nonmylenated fibers.nonmylenated fibers.
b).b). nodes of Ranviernodes of Ranvier::
spaces between the sheathsspaces between the sheaths
The action potential skips to the nodesThe action potential skips to the nodes
Nerve ImpulseNerve Impulse
A). TermsA). Terms
1).1). Resting membrane PotentialResting membrane Potential::
Change in ion concentrationChange in ion concentration
Change in ion concentration insideChange in ion concentration inside
becomes more negativebecomes more negative
4).4). Graded PotentialGraded Potential
Localized change in ion; subthresholdLocalized change in ion; subthreshold
5).5). Action PotentialAction Potential
Change in ion concentration thatChange in ion concentration that
does not decrease over distance.does not decrease over distance.
B).B). Action PotentialAction Potential
Stages of an Action PotentialStages of an Action Potential
polarized resting potentialpolarized resting potential
undershoot phaseundershoot phase
UndershooUndershoott :: the K+ channels stay openthe K+ channels stay open
once resting potential is reached;once resting potential is reached;
hyperpolarizing the cell.hyperpolarizing the cell.
Cannot be depolarized again until the membrane hasCannot be depolarized again until the membrane has
reached resting potential. The action potential moves at areached resting potential. The action potential moves at a
constant velocityconstant velocity
D).D). All or none phenomenonAll or none phenomenon
Not all depolarizations result in action potentialsNot all depolarizations result in action potentials.. TheThe
depolarization must reach thedepolarization must reach the threshold pointthreshold point
E).E). Refractory periodRefractory period
AAbsolute refractory periodbsolute refractory period cannot respond to anothercannot respond to another
RRelative refractory periodelative refractory period -- tthe threshold is higherhe threshold is higher
F). Impulse VelocityF). Impulse Velocity
Strong stimuli result in more nerve impulses NotStrong stimuli result in more nerve impulses Not
stronger impulses or fasterstronger impulses or faster
SynapseSynapse –– junction that carriesjunction that carries
information between neuronsinformation between neurons
A). TypesA). Types
1). Electrical synapse: ions to cross junction1). Electrical synapse: ions to cross junction
2). Chemical synapse2). Chemical synapse
B). Termination of neurotransmitterB). Termination of neurotransmitter
1). Degradation enzymes1). Degradation enzymes
2). Neurotransmitter reabsorbed2). Neurotransmitter reabsorbed
3). Diffusion of the neurotransmitter3). Diffusion of the neurotransmitter
releasesreleases Ca++ (in neuron)Ca++ (in neuron)
± neurotransmitter released ± binds to receptors± neurotransmitter released ± binds to receptors ±±
ion channels open on postsynaptic membraneion channels open on postsynaptic membrane
A). Excitatory Synapses
neurotransmitters results in the
depolarization of postsynaptic
membrane. Creating localized graded
(dendrites do not have action
IF THE GRADED RESPONSE IS
STRONG ENOUGH TO BE CARRIED
TO THE AXON A FULL ACTION
POTENTIAL WILL RESULT
B). Inhibitory Synapses
Binding neurotransmitters reduces
the postsynaptic membranes ability
to create an action potential.
Types of Neurotransmitters
C. Integration or Summation of Synaptic Events
It takes more than one synaptic event to create
an action potential.
Presynaptic inhibition = excitatory
neurotransmitter by one neuron + inhibitory
neurotransmitter of another neuron
Division of the Nervous
A). Central Nervous
• Brain and Spinal Cord
B). Peripheral Nervous
• Outside CNS
1). Sensory or afferent
• Carries impulses to CNS
2). Motor or efferent
• Carries impulses from the
I). Somatic Nervous System
II). Autonomic Nervous
• a. Parasympathetic
• b. Sympathetic
The SympatheticThe Sympathetic
Nervous SystemNervous System
TheThe first fibersfirst fibers of the sympathetic nerves, called theof the sympathetic nerves, called the
preganglionic fiberspreganglionic fibers, leave from the thoracic or lumbar, leave from the thoracic or lumbar
regions of the spine.regions of the spine.
Soon afterSoon after leaving the spineleaving the spine, a preganglionic fiber, a preganglionic fiber joinsjoins
other preganglionic fibersother preganglionic fibers to form anto form an autonomic ganglionautonomic ganglion..
At this point, theAt this point, the preganglionic fiber synapsespreganglionic fiber synapses on theon the
second nerve fiber of the systemsecond nerve fiber of the system, the, the postganglionic fiberpostganglionic fiber,,
andand releases acetylcholinereleases acetylcholine, which causes the, which causes the
postganglionic fiber to fire anpostganglionic fiber to fire an action potentialaction potential..
From theFrom the autonomic gangliaautonomic ganglia, the postganglionic fiber travels, the postganglionic fiber travels
to itsto its target organtarget organ, the muscle or gland., the muscle or gland.
TheThe sympathetic postganglionic fibersympathetic postganglionic fiber usually releases theusually releases the
neurotransmitter norepinephrineneurotransmitter norepinephrine.. Target organ receptors forTarget organ receptors for
norepinephrinenorepinephrine are calledare called adrenergic receptorsadrenergic receptors..
The Parasympathetic Nervous SystemThe Parasympathetic Nervous System
The fibers of the parasympathetic nervous systemThe fibers of the parasympathetic nervous system (PNS)(PNS)
leave the brain in the cranial nervesleave the brain in the cranial nerves oror leave the spinal cordleave the spinal cord
from the sacral areafrom the sacral area..
TheThe preganglionic fiberpreganglionic fiber of theof the PNSPNS is typically long and travelsis typically long and travels
to an autonomic ganglionto an autonomic ganglion locatedlocated near the target organnear the target organ..
Preganglionic parasympathetic nervesPreganglionic parasympathetic nerves releaserelease acetylcholineacetylcholine
thatthat then stimulates the postganglionic fiberthen stimulates the postganglionic fiber..
TheThe parasympathetic postganglionic fiberparasympathetic postganglionic fiber then travels a shortthen travels a short
distancedistance to its target tissueto its target tissue, a, a muscle or a glandmuscle or a gland. This nerve. This nerve
also releases acetylcholinealso releases acetylcholine..
Preganglionic acetylcholine receptorsPreganglionic acetylcholine receptors for sympathetic andfor sympathetic and
parasympathetic fibersparasympathetic fibers are calledare called nicotinic receptorsnicotinic receptors ..
Postganglionic acetylcholine receptorsPostganglionic acetylcholine receptors are calledare called muscarinicmuscarinic
receptorsreceptors. These names relate to the experimental. These names relate to the experimental
stimulation of the receptors bystimulation of the receptors by nicotinenicotine andand muscarinemuscarine (a(a
mushroom poison).mushroom poison).
Functions of the Sympathetic andFunctions of the Sympathetic and
Parasympathetic NervesParasympathetic Nerves
TheThe sympathetic nervous systemsympathetic nervous system innervates theinnervates the heartheart,,
causing ancausing an increase in heart rateincrease in heart rate andand strength of contractionstrength of contraction..
Sympathetic nervesSympathetic nerves innervateinnervate all large and small arteriesall large and small arteries
andand veinsveins, causing, causing constriction of all vesselsconstriction of all vessels except theexcept the
arterioles supplying skeletal musclearterioles supplying skeletal muscle..
Sympathetic nervesSympathetic nerves innervate theinnervate the smooth muscle of thesmooth muscle of the
gutgut, causing, causing decreased motilitydecreased motility, and the, and the smooth muscle ofsmooth muscle of
the respiratory tractthe respiratory tract, causing, causing bronchial relaxationbronchial relaxation andand
decreased bronchial secretionsdecreased bronchial secretions..
Sympathetic stimulationSympathetic stimulation affects theaffects the liverliver,, stimulatesstimulates
secretions of thesecretions of the sweat glandssweat glands, and is responsible for, and is responsible for
ejaculation during male orgasmejaculation during male orgasm..
Parasympathetic fibersParasympathetic fibers innervate theinnervate the heartheart,, slowing theslowing the
heart rateheart rate, and the, and the gutgut, causing, causing increased motilityincreased motility..
Parasympathetic nervesParasympathetic nerves innervateinnervate bronchial smoothbronchial smooth
musclemuscle, causing, causing airway constrictionairway constriction, and the, and the genitourinarygenitourinary
tracttract, causing, causing erection in the maleerection in the male..
The Autonomic Nervous System
Structure Sympathetic Stimulation Parasympathetic Stimulation
Iris (eye muscle) Pupil dilation Pupil constriction
Salivary Glands Saliva production reduced Saliva production increased
Oral/Nasal Mucosa Mucus production reduced Mucus production increased
Heart Heart rate and force increased Heart rate and force decreased
Lung Bronchial muscle relaxed Bronchial muscle contracted
Stomach Peristalsis reduced Gastric juice secreted; motility
Small Intestine Motility reduced Digestion increased
Large Intestine Motility reduced Secretions and motility increased
Liver Increased conversion of glycogen
Kidney Decreased urine secretion Increased urine secretion
Adrenal medulla Norepinephrine and epinephrine
Bladder Wall relaxed Sphincter closed Wall contracted Sphincter relaxed
THE SOMATOSENSORY SYSTEMTHE SOMATOSENSORY SYSTEM
■■ The somatosensory system relays information to theThe somatosensory system relays information to the
CNS about four major body sensations:CNS about four major body sensations:
body positionbody position..
Stimulation of receptorsStimulation of receptors on regions of the body wall ison regions of the body wall is
required torequired to initiate the sensory response.initiate the sensory response.
■■ The system is organized intoThe system is organized into dermatomesdermatomes, with each, with each
segment supplied by asegment supplied by a single dorsal root ganglionsingle dorsal root ganglion thatthat
sequentially relays the sensory information tosequentially relays the sensory information to thethe
spinal cord, the thalamus, and the sensoryspinal cord, the thalamus, and the sensory cortexcortex..
■■ Two pathwaysTwo pathways carry sensory information throughcarry sensory information through thethe
CNSCNS. The. The discriminative pathwaydiscriminative pathway crosses in thecrosses in the
medulla and relays touch and body position. Themedulla and relays touch and body position. The
anterolateral pathwayanterolateral pathway crosses in the spinal cordcrosses in the spinal cord andand
relays temperature and pain sensation fromrelays temperature and pain sensation from thethe
opposite side of the body.opposite side of the body.
The Sensory Unit
The somatosensory experience arises from
information provided by a variety of receptors
distributed throughout the body.
There are four major modalities of sensory
(1) discriminative touch, which is required to
identify the size and shape of objects and their
movement across the skin;
(2) temperature sensation;
(3) sense of movement of the limbs and joints
of the body;
(4) nociception or pain sense.
Kinds of SensitivityKinds of Sensitivity
DEFINITION OF PAINDEFINITION OF PAIN
PAINPAIN –– it is typical pathological processit is typical pathological process,,
whichwhich was generated during evolutionwas generated during evolution andand
which arise owing to action on an organismwhich arise owing to action on an organism
painfulpainful ((nociceptivenociceptive)) irritantirritant oror weakeningweakening
ofof antipainfulantipainful ((antinociceptiveantinociceptive)) systemsystem
PainPain is an “unpleasant sensory andis an “unpleasant sensory and
emotional experience associatedemotional experience associated withwith
potential tissue damage, or described inpotential tissue damage, or described in
terms ofterms of such damage.”such damage.”
• Physiological pain
• Pathological pain
• Acute pain
• Chronical pain
MEDIATORS OFMEDIATORS OF
PAINPAIN• Substanse Р
• Glutamic acid
TYPES OF PAINTYPES OF PAIN
Pain can be classified according to
site of referral, and
Cutaneous pain is a sharp, burning pain that has its
origin in the skin or subcutaneous tissues.
Deep pain is a more diffuse and throbbing pain that
originates in structures such as the muscles, bones,
and tendons and radiates to the surrounding
Visceral pain is a diffuse and poorly defined pain
that results from stretching, distention, or ischemia
of tissues in a body organ.
Referred pain is pain that originates at a visceral site
but is perceived as originating in part of the body
wall that is innervated by neurons entering the same
segment of the nervous system.
Acute pain usually results from tissue damage and
is characterized by autonomic nervous system
Chronic pain is persistent pain that is accompanied
by loss of appetite, sleep disturbances, depression,
■ Pain is both a protective and an unpleasant physical and emotionally
disturbing sensation originating in pain receptors that respond to a
number of stimuli that threaten tissue integrity.
■ There are two pathways for pain transmission:
• The fast pathway for sharply discriminated pain that moves directly
from the receptor to the spinal cord using myelinated Aδ fibers and from
the spinal cord to the thalamus using the neospinothalamic tract
• The slow pathway for continuously conducted pain that is transmitted
to the spinal cord using unmyelinated C fibers and from the spinal cord
to the thalamus using the more circuitous and slower-conducting
■ The central processing of pain information includes transmission to the
somatosensory cortex, where pain information is perceived and
interpreted; the limbic system, where the emotional components of pain
are experienced; and to brain stem centers, where autonomic nervous
system responses are recruited.
■ Modulation of the pain experience occurs by way of the endogenous
analgesic center in the midbrain, the pontine noradrenergic neurons,
and the nucleus raphe magnus in the medulla, which sends inhibitory
signals to dorsal horn neurons in the spinal cord.
Classical and non-Classical and non-
classical views of painclassical views of pain
transmission and paintransmission and pain
Classical painClassical pain
(b):(b): Normal painNormal pain..
Under basalUnder basal
conditions, pain is notconditions, pain is not
modulated by glia.modulated by glia.
(c)(c) Pain facilitation:Pain facilitation:
classical view. Inclassical view. In
response to intenseresponse to intense
and/or prolongedand/or prolonged
barrages of incomingbarrages of incoming
“pain” signals, the“pain” signals, the
PTNs becomePTNs become
sensitized and over-sensitized and over-
respond to subsequentrespond to subsequent
incoming signalsincoming signals
view. Here, glialview. Here, glial
activation isactivation is
conceptualized as aconceptualized as a
driving force fordriving force for
creating andcreating and
maintaining painmaintaining pain
Pain TheoriesPain Theories
Traditionally, two theories have been offered to explainTraditionally, two theories have been offered to explain
thethe physiologic basis for the pain experience.physiologic basis for the pain experience.
TheThe firstfirst,, specificityspecificity theorytheory, regards pain as a separate, regards pain as a separate
sensory modality evoked bysensory modality evoked by the activity of specificthe activity of specific
receptors that transmit information toreceptors that transmit information to pain centers orpain centers or
regions in the forebrain where pain is experienced.regions in the forebrain where pain is experienced.
TheThe secondsecond theory includes a group of theoriestheory includes a group of theories
collectivelycollectively referred to asreferred to as pattern theorypattern theory. It proposes that. It proposes that
pain receptorspain receptors share endings or pathways with othershare endings or pathways with other
sensory modalitiessensory modalities but that different patterns of activity
(i.e., spatial or temporal) of the same neurons can be
used to signal painful and nonpainful stimuli.
For example, light touch applied to the skin would
produce the sensation of touch through low-frequency
firing of the receptor; intense pressure would produce
pain through high-frequency firing of the same receptor.
Gate control theoryGate control theory
AA modification of specificity theory, wasmodification of specificity theory, was proposedproposed
by Melzack and Wall in 1965 to meet theby Melzack and Wall in 1965 to meet the
challengeschallenges presented by the pattern theories.presented by the pattern theories.
This theory postulated theThis theory postulated the presence of neuralpresence of neural
gating mechanisms at thegating mechanisms at the segmental spinalsegmental spinal cordcord
level to account for interactions between pain andlevel to account for interactions between pain and
othersensory modalitiesothersensory modalities..
According to theAccording to the gate control theorygate control theory, the, the
internuncialinternuncial neuronsneurons involved in the gatinginvolved in the gating
mechanismmechanism are activatedare activated by large-diameter, faster-by large-diameter, faster-
propagating fibers that carry tactilepropagating fibers that carry tactile informationinformation. The. The
simultaneous firing of the large-diametersimultaneous firing of the large-diameter touchtouch
fibersfibers has thehas the potential for blocking thepotential for blocking the
transmission oftransmission of impulsesimpulses from thefrom the small-diametersmall-diameter
myelinated and unmyelinatedmyelinated and unmyelinated pain fiberspain fibers..
More recently, Melzack has developed the neuromatrix theory to
address further the brain’s role in pain as well as the multiple
dimensions and determinants of pain. This theory is particularly useful
in understanding chronic pain and phantom limb pain, in which
there is not a simple one-to-one relationship between tissue injury and
The neuromatrix theory proposes that the brain contains a widely
distributed neural network, called the body-self neuromatrix, that
contains somatosensory, limbic, and thalamocortical componentssomatosensory, limbic, and thalamocortical components.
Genetic and sensory influences determine the synaptic
architecture of an individual’s neuromatrix that integrates multiple
sources of input and evokes the sensory, affective, and cognitive
dimensions of pain experience and behavior.
These multiple input sources include:
other sensory impulses affecting interpretation of the situation;
inputs from the brain addressing such things as attention, expectation,
culture, and personality;
intrinsic neural inhibitory modulation;
various components of stress-regulation systems.
• Damage to these pathways produces a deficit
in pain and temperature discrimination and
may also produce abnormal painful
sensations (dysesthesias) usually in the
area of sensory loss. Such pain is termed
neuropathic pain and often has a strange
burning, tingling, or electric shocklike quality.
It may arise from several mechanisms.
• Damaged peripheral nerve fibers become
highly mechanosensitive and may fire
spontaneously without known stimulation.
They also develop sensitivity to
norepinephrine released from sympathetic
• Electrical impulses may spread abnormally
from one fiber to another (ephaptic
conduction), enhancing the spontaneous
firing of multiple fibers.
• Neuropeptides released by injured nerves
may recruit an inflammatory reaction that
stimulates pain. In the dorsal horn,
denervated spinal neurons may become
• In the brain and spinal cord, synaptic
reorganization occurs in response to injury
and may lower the threshold for pain. In
addition, inhibition of pathways that modulate
transmission of sensory information in the
spinal cord and brainstem may promote
Free nerve endingsFree nerve endings of unmyelinatedof unmyelinated
C fibers and small-diameter myelinatedC fibers and small-diameter myelinated
AAδδ fibers in the skin convey sensoryfibers in the skin convey sensory
information in response toinformation in response to chemical,chemical,
thermal, and mechanical stimulithermal, and mechanical stimuli..
Intense stimulationIntense stimulation of these nerveof these nerve
endingsendings evokes the sensation of painevokes the sensation of pain..
In contrast to skin, most deep tissuesIn contrast to skin, most deep tissues
are relatively insensitive to chemical orare relatively insensitive to chemical or
noxious stimuli.noxious stimuli.
However, inflammatory conditions canHowever, inflammatory conditions can
sensitize sensory afferents from deepsensitize sensory afferents from deep
tissues to evoke pain on mechanicaltissues to evoke pain on mechanical
stimulation. This sensitization appearsstimulation. This sensitization appears
to beto be mediated bymediated by bradykinin,bradykinin,
prostaglandins, and leukotrienesprostaglandins, and leukotrienes
released during the inflammatoryreleased during the inflammatory
Information fromInformation from primary afferent fibersprimary afferent fibers
is relayedis relayed via sensory gangliavia sensory ganglia to theto the
dorsal horn of the spinal corddorsal horn of the spinal cord and thenand then
to theto the contralateral spinothalamic tractcontralateral spinothalamic tract,,
which connects towhich connects to thalamic neuronsthalamic neurons
that project to thethat project to the somatosensorysomatosensory
Characteristics ofCharacteristics of
Acute and Chronic PainAcute and Chronic Pain
Characteristic Acute Pain Chronic Pain
Onset Recent Continuous or intermittent
Duration Short duration (<6 months) 6 months or more
Consistent with sympathetic fight-
Increased heart rate
Increased stroke volume
Increased blood pressure
Increased pupillary dilation
Increased muscle tension
Decreased gut motility
Decreased salivary flow (dry mouth)
Absence of autonomic
Withdrawal from outside
Decreased strength of
Other types of
Pain Threshold and Tolerance
Cando Baseline Dolorimeter
Pain threshold and tolerance affect an
individual’s response to a painful stimulus.
Although the terms often are used
interchangeably, pain threshold and pain
tolerance have distinct meanings. Pain
threshold is closely associated with tissue
damage and the point at which a stimulus is
perceived as painful.
Pain tolerance relates more to the total pain
experience; it is defined as the maximum
intensity or duration of pain that a person is
willing to endure before the person wants
something done about the pain.
Psychological, familial, cultural, and
environmental factors significantly influence
the amount of pain a person is willing to
tolerate. The threshold to pain is fairly uniform
from one person to another, whereas pain
tolerance is extremely variable. Separation
and identification of the role of each of
these two aspects of pain continue to pose
fundamental problems for the pain
management team and for pain researchers.
Alterations in Pain Sensitivity
Hypersensitivity (i.e., hyperesthesia) or increased painfulness (i.e.,
Primary hyperalgesia occurs at the site of injury.
Secondary hyperalgesia occurs in nearby uninjured tissue.
Hyperpathia is a syndrome in which the sensory threshold is raised,
but when it is reached, continued stimulation, especially if repetitive,
results in a prolonged and unpleasant experience. This pain can be
explosive and radiates through a peripheral nerve distribution. It is
associated with pathologic changes in peripheral nerves, such as
Spontaneous, unpleasant sensations called paresthesias occur with
more severe irritation (e.g., the pins-and-needles sensation that
follows temporary compression of a peripheral nerve).
The general term dysesthesia is given to distortions (usually
unpleasant) of somesthetic sensation that typically accompany partial
loss of sensory innervation.
Alterations in Pain Sensitivity
• Severe pathologic processes can result in reduced or lost
tactile (e.g., hypoesthesia, anesthesia), temperature (e.g.,
hypothermia, athermia), and pain sensation (i.e.,
• Analgesia is the absence of pain on noxious stimulation or
the relief of pain without loss of consciousness. The inability to
sense pain may result in trauma, infection, and even loss of a
body part or parts. Inherited insensitivity to pain may take the
form of congenital indifference or congenital insensitivity to
• Allodynia (Greek allo, “other,” and odynia, “painful”) is the
term used for the puzzling phenomenon of pain that follows a
non-noxious stimulus to apparently normal skin. This term is
intended to refer to instances in which otherwise normal
tissues may be abnormally innervated or may be referral sites
for other loci that give rise to pain with non-noxious stimuli.
• Trigger points are highly localized points on the skin or
mucous membrane that can produce immediate intense pain
at that site or elsewhere when stimulated by light tactile
NeuralgiaNeuralgia is characterized by severe, brief,is characterized by severe, brief,
often repetitive attacksoften repetitive attacks of lightning-like orof lightning-like or
throbbing pain. It occurs along the distributionthrobbing pain. It occurs along the distribution ofof
a spinal or cranial nerve and usually isa spinal or cranial nerve and usually is
precipitatedprecipitated by stimulation of the cutaneousby stimulation of the cutaneous
region supplied by that nerve.region supplied by that nerve.
Trigeminal Neuralgia.Trigeminal Neuralgia.
Trigeminal neuralgia, orTrigeminal neuralgia, or tictic
douloureuxdouloureux,, is one of theis one of the
most common and severemost common and severe
neuralgias. It is manifestedneuralgias. It is manifested
byby facial ticsfacial tics oror grimacesgrimaces
and characterized byand characterized by
attacks of pain that usuallyattacks of pain that usually
are limited to the unilateralare limited to the unilateral
sensory distribution of onesensory distribution of one
or more branches of theor more branches of the
trigeminal nerve, mosttrigeminal nerve, most
often the maxillary oroften the maxillary or
mandibular divisions.mandibular divisions.
Postherpetic Neuralgia.Postherpetic Neuralgia.
Postherpetic pain is painPostherpetic pain is pain
that persiststhat persists as aas a
complication of herpescomplication of herpes
zoster or shingles. Itzoster or shingles. It
describes thedescribes the presence ofpresence of
pain more than 1 monthpain more than 1 month
after the onset of theafter the onset of the
Postherpetic neuralgiaPostherpetic neuralgia
develops in from 10% todevelops in from 10% to
70% of70% of patients withpatients with
shingles; the riskshingles; the risk
increases with age.increases with age.
The pain ofThe pain of postherpeticpostherpetic
neuralgia occurs in theneuralgia occurs in the
areas of innervation ofareas of innervation of
thethe infected gangliainfected ganglia..
During the acute attack ofDuring the acute attack of
herpes zosterherpes zoster, the, the
reactivated virus travelsreactivated virus travels
from the ganglia to thefrom the ganglia to the
skin of the correspondingskin of the corresponding
dermatomes, causingdermatomes, causing
localized vesicularlocalized vesicular
eruptioneruption and hyperpathiaand hyperpathia
((i.e.i.e., abnormally, abnormally
exaggerated subjectiveexaggerated subjective
responseresponse to pain).to pain).
Phantom Limb Pain
• Phantom limb pain, a type of
neurologic pain, follows
amputation of a limb or part of a
limb. As many as 70% of those
who under amputation
experience phantom pain.
• The pain often begins as
sensations of tingling, heat and
cold, or heaviness, followed by
burning, cramping, or shooting
pain. It may disappear
spontaneously or persist for
many years. One of the more
troublesome aspects of phantom
pain is that the person may
experience painful sensations
that were present before the
amputation, such as that of a
painful ulcer or bunion.
• Several theories have been proposed as to the causes of phantom pain.
• One theory is that the end of a regenerating nerve becomes trapped in the scar
tissue of the amputation site. It is known that when a peripheral nerve is cut, the scar
tissue that forms becomes a barrier to regenerating outgrowth of the axon. The
growing axon often becomes trapped in the scar tissue, forming a tangled growth
(i.e., neuroma) of smalldiameter axons, including primary nociceptive afferents and
sympathetic efferents. It has been proposed that these afferents show increased
sensitivity to innocuous mechanical stimuli and to sympathetic activity and circulating
• A related theory moves the source of phantom limb pain to the spinal cord,
suggesting that the pain is caused by the spontaneous firing of spinal cord neurons
that have lost their normal sensory input from the body. In this case, a closed
self-exciting neuronal loop in the posterior horn of the spinal cord is postulated to
send impulses to the brain, resulting in pain. Even the slightest irritation to the
amputated limb area can initiate this cycle.
• Other theories propose that the phantom limb pain may arise in the brain. In one
hypothesis, the pain is caused by changes in the flow of signals through
somatosensory areas of the brain.
• Treatment of
phantom limb pain
accomplished by the
use of sympathetic
blocks, TENS of the
the area, hypnosis,
Antinociceptive systemsAntinociceptive systems
NeuronalNeuronal opiate systemopiate system –– metmet-- and leuencephalinand leuencephalin
NeuronalNeuronal unopiate systemunopiate system –– noradrenalinnoradrenalin,, serotoninserotonin,,
HormonalHormonal opiate systemopiate system –– hormoneshormones ofof
HormonalHormonal unopiate systemunopiate system –– vasopressinvasopressin
1.1. Opening of abscessOpening of abscess
2.2. Reposition ofReposition of
3.3. Splintation of extremitySplintation of extremity
4.4. Section of scarsSection of scars
7.7. Magnetico-laserMagnetico-laser therapytherapy
9.9. ManualManual therapytherapy
METHODS OFMETHODS OF
5.5. CorrectCorrect stereotypestereotype of motionof motion
6.6. Self-removel of painSelf-removel of pain
Upper Motor NeuronsUpper Motor Neurons
Planned movements and those guided by sensory,
visual, or auditory stimuli are preceded by
discharges from prefrontal, somatosensory, visual,
or auditory cortices, which are then followed by
motor cortex pyramidal cell discharges that occur
several milliseconds before the onset of movement
TheThe motor cortexmotor cortex is theis the
region from whichregion from which
movements can be elicitedmovements can be elicited
by electrical stimuli (Figure).by electrical stimuli (Figure).
the primary motor area
(Brodmann area 4),
premotor cortex (area 6),
cortex (medial portions of
primary sensory cortex
(areas 3, 1, and 2).
In the motor cortex, groups
of neurons are organized in
vertical columns, and
discrete groups control
contraction of individual
► Cortical motor neuronsCortical motor neurons contribute axons thatcontribute axons that
converge in the corona radiata and descend in theconverge in the corona radiata and descend in the
posterior limb of the internal capsule, cerebralposterior limb of the internal capsule, cerebral
peduncles, ventral pons, and medullapeduncles, ventral pons, and medulla. These fibers. These fibers
constitute theconstitute the corticospinalcorticospinal andand corticobulbarcorticobulbar
tractstracts and together areand together are known asknown as upper motorupper motor
neuron fibersneuron fibers. As they descend through the. As they descend through the
diencephalon and brainstem, fibers separate todiencephalon and brainstem, fibers separate to
innervate extrapyramidal and cranial nerve motorinnervate extrapyramidal and cranial nerve motor
nuclei. The lower brainstem motor neurons receivenuclei. The lower brainstem motor neurons receive
input from crossed and uncrossed corticobulbarinput from crossed and uncrossed corticobulbar
fibers, although neurons that innervate lower facialfibers, although neurons that innervate lower facial
muscles receive primarily crossed fibers.muscles receive primarily crossed fibers.
► In the ventral medullaIn the ventral medulla, the remaining corticospinal, the remaining corticospinal
fibers course in a tract that is pyramidal in shape infibers course in a tract that is pyramidal in shape in
cross section—thus, the namecross section—thus, the name pyramidal tractpyramidal tract.. AtAt
thethe lower end of the medullalower end of the medulla, most fibers, most fibers
decussate, although the proportion of crossed anddecussate, although the proportion of crossed and
uncrossed fibers varies somewhat betweenuncrossed fibers varies somewhat between
individuals. The bulk of these fibers descend as theindividuals. The bulk of these fibers descend as the
lateral corticospinal tractlateral corticospinal tract of the spinal cord.of the spinal cord.
► Different groups ofDifferent groups of neurons in the cortex controlneurons in the cortex control
muscle groupsmuscle groups of the contralateral face, arm, andof the contralateral face, arm, and
legleg. Neurons near the ventral end of the central. Neurons near the ventral end of the central
sulcus control muscles of the face, whereassulcus control muscles of the face, whereas
neurons on the medial surface of the hemisphereneurons on the medial surface of the hemisphere
control leg muscles. Because thecontrol leg muscles. Because the movements of themovements of the
face, tongue, and hand are complex in humans, aface, tongue, and hand are complex in humans, a
large share of the motor cortex is devoted to theirlarge share of the motor cortex is devoted to their
controlcontrol. A. A somatotopic organizationsomatotopic organization is also apparentis also apparent
in thein the lateral corticospinal tractlateral corticospinal tract of the cervicalof the cervical
cord, where fibers to motor neurons that control legcord, where fibers to motor neurons that control leg
muscles lie laterally and fibers to cervical motormuscles lie laterally and fibers to cervical motor
neurons lie medially.neurons lie medially.
Upper and Lower motoneurons innervate the skeletal
muscles and are essential for motor function.
Amyotrophic lateral sclerosis (ALS), fatal combined degeneration of
motoneurons and motor fiber tracts (i.e. combined gray and white matter disease).
Motoneurons of entire neuraxis! ALS - most devastating neurodegenerative
disease of aging CNS that so resembles Alzheimer and Parkinson diseases.
Upper and Lower motoneurons innervate the skeletal
muscles and are essential for motor function.
• Amyotrophic lateral sclerosis (ALS), also known as Lou
Gehrig’s disease after the famous New York Yankees
baseball player, is a devastating neurologic disorder that
selectively affects motor function. ALS is primarily a disorder
of middle to late adulthood, affecting persons between 55
and 60 years of age, with men developing the disease nearly
twice as often as women.
• Neuron degeneration, atrophy, and loss → glial replacement.
No inflammation! Degeneration of motoneurons:
• 1. Motor cortex (pyramidal cells in precentral cortex) → loss
of large myelinated fibers in anterior & lateral spinal
columns (gliotic sclerosis of lateral columns = LATERAL
N.B. posterior columns are usually spared in SALS.N.B. posterior columns are usually spared in SALS.
• 2. Brain stem - lower nuclei are more often / more
extensively involved than upper nuclei (e.g. oculomotor
nuclei loss is modest and rarely demonstrable clinically,
whereas hypoglossal nuclei are prominently degenerated).
• 3. Spinal anterior horns → loss of myelinated fibers in
anterior root →muscle denervation atrophy
(AMYOTROPHY); reinnervation is possible (but much less
extensive as in poliomyelitis, peripheral neuropathy).
Amyotrophic lateral sclerosisAmyotrophic lateral sclerosis
Cytoplasmic ultrastructural abnormalities (cytoskeleton is affectedCytoplasmic ultrastructural abnormalities (cytoskeleton is affected
1) in proximal motor axons - strongly argentophilic1) in proximal motor axons - strongly argentophilic SPHEROIDSSPHEROIDS
(accumulated(accumulated neurofilament bundlesneurofilament bundles that may contain other cytoplasmicthat may contain other cytoplasmic
structures, such as mitochondria).structures, such as mitochondria).
some patients have mutations insome patients have mutations in neurofilament heavy chain subunitneurofilament heavy chain subunit
abnormal neurofilaments interfere with axonal transport, resulting inabnormal neurofilaments interfere with axonal transport, resulting in
failure to maintain axonal structure and transport of macromoleculesfailure to maintain axonal structure and transport of macromolecules
such as neurotrophic factors required for motor neuron survival.such as neurotrophic factors required for motor neuron survival.
2)2) Bunina bodiesBunina bodies - tiny round eosinophilic structures.- tiny round eosinophilic structures.
3)3) Lewy body-like eosinophilic inclusionsLewy body-like eosinophilic inclusions (immunoreactive to(immunoreactive to
neurofilaments, ubiquitinneurofilaments, ubiquitin ((marker for degenerationmarker for degeneration)), and gene encoding, and gene encoding
Cu/Zn superoxide dismutase [SOD1]).Cu/Zn superoxide dismutase [SOD1]).
Number of abnormalities inNumber of abnormalities in GLUTAMATEGLUTAMATE metabolism have beenmetabolism have been
identified in ALS (incl. alterations in tissue glutamate levels, transporteridentified in ALS (incl. alterations in tissue glutamate levels, transporter
proteins, postsynaptic receptors) - primary or secondary events?proteins, postsynaptic receptors) - primary or secondary events?
60% patients have60% patients have large decrease in GLUTAMATE TRANSPORTlarge decrease in GLUTAMATE TRANSPORT
activity*activity* in motor cortex and spinal cord (but not in other regions ofin motor cortex and spinal cord (but not in other regions of
central nervous system) → ↑ extracellular levels of glutamate →central nervous system) → ↑ extracellular levels of glutamate →
*loss of astrocytic*loss of astrocytic glutamate transporter protein EAAT2glutamate transporter protein EAAT2 (due to defect in(due to defect in
mRNA splicing).mRNA splicing).
InIn myelinated nervesmyelinated nerves, the axon between two nodes of Ranvier (internodal, the axon between two nodes of Ranvier (internodal
segment) is surrounded by asegment) is surrounded by a myelin sheathmyelin sheath. This is a precondition for. This is a precondition for
saltatory conduction of the action potentials, i.e., the “jumping” propagationsaltatory conduction of the action potentials, i.e., the “jumping” propagation
of excitation from one nodal constriction (R1) to the next (R2). Theof excitation from one nodal constriction (R1) to the next (R2). The
internodal segment itself cannot generate an action potential, i.e.,internodal segment itself cannot generate an action potential, i.e.,
depolarization of the second node (R2) is completely dependent on thedepolarization of the second node (R2) is completely dependent on the
current from the first node (R1). However, the current is usually so strongcurrent from the first node (R1). However, the current is usually so strong
that it can even jump across the nodes.that it can even jump across the nodes.
Nevertheless, on the way along the internodal segment the amplitude of theNevertheless, on the way along the internodal segment the amplitude of the
current will diminish. First of all, the membrane in the internodal segmentcurrent will diminish. First of all, the membrane in the internodal segment
must change its polarity, i.e., themust change its polarity, i.e., the membrane capacitancemembrane capacitance must bemust be
discharged, for which a current is needed. Secondly, current can alsodischarged, for which a current is needed. Secondly, current can also
escape through individualescape through individual ionic channelsionic channels in the axonal membrane (orangein the axonal membrane (orange
arrow). However, myelination of the internodal segment causes thearrow). However, myelination of the internodal segment causes the
membrane resistance (Rm) to be elevated and the capacity (Cm) of themembrane resistance (Rm) to be elevated and the capacity (Cm) of the
membrane condensor to be reduced.membrane condensor to be reduced.
TheThe resistanceresistance of the axonal membrane of the internodal segment is veryof the axonal membrane of the internodal segment is very
high because of the low density of ionic channels there. Furthermore, thehigh because of the low density of ionic channels there. Furthermore, the
perimembranous space is insulated by a layer of fat from the freeperimembranous space is insulated by a layer of fat from the free
extracellular space. The lowextracellular space. The low capacitancecapacitance of the condensor is due to theof the condensor is due to the
large distance between the interior of the axon and the free extracellularlarge distance between the interior of the axon and the free extracellular
space as well as the low polarity of the fatty material in the space betweenspace as well as the low polarity of the fatty material in the space between
DemyelinationDemyelination can becan be
caused by degenerative,caused by degenerative,
toxic, or inflammatorytoxic, or inflammatory
damage to the nerves,damage to the nerves,
or by a deficiency ofor by a deficiency of
vitamins B6 or B12.vitamins B6 or B12.
If this happens, Rm willIf this happens, Rm will
be reduced and Cmbe reduced and Cm
raised in the internodalraised in the internodal
As a result, more currentAs a result, more current
will be required towill be required to
change the polarity ofchange the polarity of
the internodal segmentthe internodal segment
and, through opening upand, through opening up
the ionic channels, largethe ionic channels, large
losses of current maylosses of current may
Multiple SclerosisMultiple Sclerosis
• Multiple sclerosis (MS), a demyelinating disease of the CNS, is a major cause of
neurologic disability among young and middleaged adults. Approximately two thirds
of persons with MS experience their first symptoms between 20 and 40 years of age.
In approximately 80% of the cases, the disease is characterized by exacerbations
and remissions over many years in several different sites in the CNS.
• Initially, there is normal or nearnormal neurologic function between exacerbations. As
the disease progresses, there is less improvement between exacerbations and
increasing neurologic dysfunction.
Huntington's diseaseHuntington's disease
Huntington's diseaseHuntington's disease is inherited as anis inherited as an
autosomal dominant disorder.autosomal dominant disorder.
When disease onset occurs later in life,When disease onset occurs later in life,
patients develop involuntary, rapid, jerkypatients develop involuntary, rapid, jerky
movements (movements (choreachorea) and slow writhing) and slow writhing
movements of the proximal limbs and trunkmovements of the proximal limbs and trunk
When disease onset occurs earlier in life,When disease onset occurs earlier in life,
patients develop signs of parkinsonism withpatients develop signs of parkinsonism with
tremor (cogwheeling) and stiffness. Thetremor (cogwheeling) and stiffness. The
spinyspiny GABAergic neuronsGABAergic neurons of the striatumof the striatum
preferentially degenerate, resulting in a netpreferentially degenerate, resulting in a net
decrease in GABAergic output from thedecrease in GABAergic output from the
striatum. This contributes to thestriatum. This contributes to the
development of chorea and athetosis.development of chorea and athetosis.
DopamineDopamine antagonists, which blockantagonists, which block
inhibition of remaining striatal neurons byinhibition of remaining striatal neurons by
dopaminergic striatal fibers, reduce thedopaminergic striatal fibers, reduce the
involuntary movements. Neurons in deepinvoluntary movements. Neurons in deep
layers of the cerebral cortex alsolayers of the cerebral cortex also
degenerate early in the disease, and laterdegenerate early in the disease, and later
this extends to other brain regions, includingthis extends to other brain regions, including
the hippocampus and hypothalamus.the hippocampus and hypothalamus.
Thus, the disease is characterized byThus, the disease is characterized by
cognitive defects and psychiatriccognitive defects and psychiatric
disturbances in addition to the movementdisturbances in addition to the movement
HUNTINGTON DISEASEHUNTINGTON DISEASE
Classical familial,Classical familial,
genetic diseasegenetic disease
motor loss andmotor loss and
““chorea”, i.e.chorea”, i.e.
Progressive, fatalProgressive, fatal
Atrophy of basalAtrophy of basal
ganglia, i.e.,ganglia, i.e.,
corpus striatumcorpus striatum Cortical (basal ganglia) atrophyCortical (basal ganglia) atrophy
Ventricular enlargementVentricular enlargement
Discriminative SensationDiscriminative Sensation
Primary sensory cortex providesPrimary sensory cortex provides
awareness of somatosensory informationawareness of somatosensory information
and the ability to make sensoryand the ability to make sensory
Touch, pain, temperature, and vibrationTouch, pain, temperature, and vibration
sense are considered the primarysense are considered the primary
modalities of sensation and are relativelymodalities of sensation and are relatively
preserved in patients with damage topreserved in patients with damage to
sensory cortex or its projections from thesensory cortex or its projections from the
In contrast, complex tasks that requireIn contrast, complex tasks that require
integration of multiple somatosensoryintegration of multiple somatosensory
stimuli and of somatosensory stimuli withstimuli and of somatosensory stimuli with
auditory or visual information are impaired.auditory or visual information are impaired.
These include the ability to distinguishThese include the ability to distinguish twotwo
pointspoints from one when touched on the skinfrom one when touched on the skin
((two-point discriminationtwo-point discrimination), localize tactile), localize tactile
stimuli, perceive the position of body partsstimuli, perceive the position of body parts
in space, recognize letters or numbersin space, recognize letters or numbers
drawn on the skin (drawn on the skin (graphesthesiagraphesthesia), and), and
identify objects by their shape, size, andidentify objects by their shape, size, and
texture (texture (stereognosisstereognosis).).
Anatomy of Sensory LossAnatomy of Sensory Loss
The patterns of sensory loss often indicate
the level of nervous system involvement.
Symmetric distal sensory loss in the limbs,
affecting the legs more than the arms,
usually signifies a generalized disorder of
multiple peripheral nerves
Sensory symptoms and deficits may be
restricted to the distribution of a single
peripheral nerve (mononeuropathy) or
two or more peripheral nerves
Symptoms limited to a dermatome indicate
a spinal root lesion (radiculopathy).
Alterations in Motor Responses andAlterations in Motor Responses and
Abnormal motor responses include inappropriate or absentAbnormal motor responses include inappropriate or absent
movements in response to painful stimuli. Brainstem reflexesmovements in response to painful stimuli. Brainstem reflexes
such as sucking and grasping responses will occur if highersuch as sucking and grasping responses will occur if higher
brain centers have been damaged.brain centers have been damaged.
Flexion and rigidity of limbs also are motor responses indicativeFlexion and rigidity of limbs also are motor responses indicative
of brain damage.of brain damage.
Muscle conditionsMuscle conditions that indicate abnormal brain function includethat indicate abnormal brain function include
hyperkinesiahyperkinesia ((excessive muscle movementsexcessive muscle movements),), hypokinesiahypokinesia
((decreased muscle movementsdecreased muscle movements),), paresisparesis ((muscle weaknessmuscle weakness),),
andand paralysisparalysis ((loss of motor functionloss of motor function).).
Specific loss of cerebral cortex functioning, but no loss ofSpecific loss of cerebral cortex functioning, but no loss of
brainstem function, results in a particular body posture calledbrainstem function, results in a particular body posture called
flexor posturingflexor posturing..
Flexor posturingFlexor posturing is characterized by flexion of the upperis characterized by flexion of the upper
extremities at the elbows and external rotation and extension ofextremities at the elbows and external rotation and extension of
the lower extremities. This posturethe lower extremities. This posture may be unilateral ormay be unilateral or
bilateralbilateral. Extensor posturing occurs with severe injury to higher. Extensor posturing occurs with severe injury to higher
brain centers and the brainstem and is characterized bybrain centers and the brainstem and is characterized by rigidrigid
extension of the limbs and neckextension of the limbs and neck..
In the spinal cord, segregation of fiber tracts and the
somatotopic arrangement of fibers give rise to distinct
patterns of sensory loss. Loss of pain and
temperature sensation on one side of the body
and of proprioception on the opposite side occurs
with lesions that involve one half of the cord on the
side of the proprioceptive deficit (Brown-Séquard
Compression of the upper spinal cord causes loss of
pain, temperature, and touch sensation first in
the legs, because the leg spinothalamic fibers are
most superficial. More severe cord compression
compromises fibers from the trunk. In patients with
spinal cord compression, the lesion is often above
the highest dermatome involved in the deficit. Thus,
radiographic studies should be tailored to visualize
the cord at and above the level of the sensory deficit
detected on examination.
Intrinsic cord lesions that involve the central portions
of the cord often impair pain and temperature
sensation at the level of the lesion because the fibers
crossing the anterior commissure and entering the
spinothalamic tracts are most centrally situated.
Thus, enlargement of the central cervical canal in
syringomyelia typically causes loss of pain and
temperature sensation across the shoulders and
Segmental Sensorimotor Function Dressing, Eating Elimination Mobility
C1 Little or no sensation or control of head and
neck; no diaphragm control; requires
Dependent Dependent Limited. Voice or sip-n-puff
controlled electric wheelchair
Head and neck sensation; some neck
control. Independent of mechanical
ventilation for short periods
Dependent Dependent Same as for C1
C4 Good head and neck sensation and motor
control; some shoulder elevation;
Dependent; may be
able to eat with
Dependent Limited to voice, mouth, head,
chin, or shoulder-controlled
C5 Full head and neck control; shoulder
strength; elbow flexion
Maximal assistance Electric or modified manual
wheel chair, needs transfer
C6 Fully innervated shoulder; wrist extension
Independent or with
Independent or with
Independent in transfers and
Full elbow extension; wrist plantar flexion;
some finger control
Independent Independent Independent; manual
Full hand and finger control; use of
intercostal and thoracic muscles
Independent Independent Independent; manual
Abdominal muscle control, partial to good
balance with trunk muscles
Independent Independent Independent; manual
Hip flexors, hip abductors (L1–3); knee
extension (L2–4); knee flexion and ankle
Independent Independent Short distance to full
ambulation with assistance
Full leg, foot, and ankle control;
innervation of perineal muscles for
bowel, bladder, and sexual function
Independent Normal to impaired
bowel and bladder
Ambulate independently with or
Functional Abilities by Level of Cord InjuryFunctional Abilities by Level of Cord Injury
• IMMEDIATE FLACCID PARALYSIS & SENSORY LOSS
BELOW THE LEVEL OF LESION
• BULBOCAVERNOUS REFLEX IS LOST BUT REUTRNS
AFTER A FEW HRS
• OTHER REFLEXES REMAIN ABSENT
• 3-6 WKS
UTONOMIC DISTURBANCES:UTONOMIC DISTURBANCES:
WEATING IS ABOLISHED
BELOW THE LEVEL OF INJURY
RINE & FECES RETAINED
LOW, & STEADY PULSE
• REPLACE SPINAL SHOCK AFTER 2-3
WEEKS IF LUMBO-SACRAL SEGMENTS
• OCCURS IN ACUTE SPINAL INJURY,
NOT IN PROGRESSIVE ONES
• AUTOMATIC BLADDER; REFLEX
SWEATING & DEFECATION
• FIRST SIGN OF WEARING OFF:
– CONTRACTION OF HAMSTRING
– FLEXION/ EXTENSION OF TOES WITH
ParalysisParalysis is the loss of sensory and voluntary motoris the loss of sensory and voluntary motor
function. With spinal cord transection, paralysis isfunction. With spinal cord transection, paralysis is
ParalysisParalysis of theof the upper and lower extremitiesupper and lower extremities occurs withoccurs with
transection of the cord at level C6 or higher and is calledtransection of the cord at level C6 or higher and is called
ParalysisParalysis of the lower half of the body occurs withof the lower half of the body occurs with
transection of the cord below C6 and is calledtransection of the cord below C6 and is called
If only one half of the cord is transectedIf only one half of the cord is transected,, hemiparalysishemiparalysis
may occur.may occur.
Permanent paralysisPermanent paralysis may occur even when the cord ismay occur even when the cord is
not transected, as a result of the destruction of thenot transected, as a result of the destruction of the
nerves following cordnerves following cord hemorrhage and swellinghemorrhage and swelling..
In addition, demyelination of the axons in the cord canIn addition, demyelination of the axons in the cord can
lead to clinically complete lesions, even though thelead to clinically complete lesions, even though the
spinal cord may not be transected.spinal cord may not be transected.
DemyelinationDemyelination of the axons most likely occurs as part ofof the axons most likely occurs as part of
the inflammatory response to cord injury.the inflammatory response to cord injury.
• Loss of sensation,
motor control, and
reflexes below the
level of injury, and
up to two levels
above, will occur.
will reflect ambient
blood pressure will
• The pulse rate is
often normal, with
low blood pressure.
• If damage and swelling around the cord is in the
cervical spine (down to approximately C5),
respirations may cease because of compression of
the phrenic nerve, which exits between C3 and C5
and controls the movement of the diaphragm.
• Autonomic hyper-reflexia is characterized by high
blood pressure with bradycardia (low heart rate),
and sweating and flushing of the skin on the face
and upper torso.
• In the past, individuals suffering from a C2 or higher
transection invariably died as a result of respiratory
arrest. Although this is still true for many, recent
advances in treatment modalities and better
emergency rescue service responses have resulted
in the survival of many individuals with high cord
• A severe spinal cord injury affects virtually all
systems of the body to some degree. Commonly,
urinary tract and kidney infections, skin breakdown
and the development of pressure ulcers, and muscle
atrophy occur. Depression, marital and family
stress, loss of income, and large medical expenses
are some of the psychosocial complications.
Dysphasia is impairment of language comprehension or production.is impairment of language comprehension or production.
Aphasia is total loss of language comprehension or production.Aphasia is total loss of language comprehension or production.
Dysphasia usually results from cerebral hypoxia, which is oftenDysphasia usually results from cerebral hypoxia, which is often
associated with a stroke but can result from trauma or infection. Brainassociated with a stroke but can result from trauma or infection. Brain
damage leading to dysphasia usually involves the left cerebraldamage leading to dysphasia usually involves the left cerebral
Broca's dysphasia results from damage to Broca's area in the frontalresults from damage to Broca's area in the frontal
lobe. Persons with Broca's dysphasia will understand language, butlobe. Persons with Broca's dysphasia will understand language, but
their ability to meaningfully express words in speech or writing will betheir ability to meaningfully express words in speech or writing will be
impaired. This is called expressive dysphasia.impaired. This is called expressive dysphasia.
Wernicke's dysphasia results from damage to Wernicke's area in theresults from damage to Wernicke's area in the
left temporal lobe. With Wernicke's dysphasia, verbal expression ofleft temporal lobe. With Wernicke's dysphasia, verbal expression of
language is intact, but meaningful understanding of spoken or writtenlanguage is intact, but meaningful understanding of spoken or written
words is impaired. This is called receptive dysphasia.words is impaired. This is called receptive dysphasia.
Agnosia is the failure to recognize an object because of the inabilityis the failure to recognize an object because of the inability
to make sense of incoming sensory stimuli. Agnosia may be visual,to make sense of incoming sensory stimuli. Agnosia may be visual,
auditory, tactile, or related to taste or smell. Agnosia develops fromauditory, tactile, or related to taste or smell. Agnosia develops from
damage to a particular primary or associative sensory area in thedamage to a particular primary or associative sensory area in the
cerebral cortex.cerebral cortex.
Alterations in Pupil Responses
• The ability of our eyes to dilate or
constrict, rapidly and equally,
depends on an intact brainstem.
• Cerebral hypoxia and many drugs
change pupil size and reactivity.
Therefore, pupil size and reactivity
offer valuable information concerning
brain integrity and function.
• Important pupil changes seen with
brain damage are pinpoint pupils
seen with opiate (heroin) overdose
and bilaterally fixed and dilated pupils
usually seen with severe hypoxia.
• Fixed pupils are typically seen with
• Brainstem injury presents with pupils
fixed bilaterally in the midposition.
DISORDERS OF THE RETINAL
■ The blood supply for the
retina is derived from
the central retinal
artery, which supplies
blood flow for the
entire inside of the
retina, and from
vessels in the choroid,
which supply the rods
■ Central retinal occlusion
interrupts blood flow to
the inner retina and
results in unilateral
■ The retinopathies,
which are disorders of
the retinal vessels,
interrupt blood flow to
the visual receptors,
leading to visual
■ Retinal detachment
separates the visual
receptors from the
provides their major
Fundus of the eye
as seen in retinal
examination with an
and hard exudates
Some exudates are
others radiate from
the fovea to form a
DISORDERS OFDISORDERS OF
THE MIDDLE EARTHE MIDDLE EAR
■ The middle ear is a small air-filled
compartment in the temporal bone.
It is separated from the outer ear
by the tympanic membrane,
contains tiny bony ossicles that aid
in the amplification and
transmission of sound to the inner
ear, and is ventilated by the
eustachian tube, which is
connected to the nasopharynx.
■■ The eustachian tube, which is lined with a mucousThe eustachian tube, which is lined with a mucous membrane that ismembrane that is
continuous with the nasopharynx,continuous with the nasopharynx, provides a passageway forprovides a passageway for
pathogens to enter thepathogens to enter the middle ear.middle ear.
■■ Otitis media (OM) refers to inflammation of the middleOtitis media (OM) refers to inflammation of the middle ear, usuallyear, usually
associated with an acute infectionassociated with an acute infection (acute OM) or an accumulation of(acute OM) or an accumulation of
fluid (OME). Itfluid (OME). It commonly is associated with disorders of eustachiancommonly is associated with disorders of eustachian
tube function.tube function.
■■ Impaired conduction of sound waves and hearingImpaired conduction of sound waves and hearing loss occur when theloss occur when the
tympanic membrane has beentympanic membrane has been perforated; air in the middle ear hasperforated; air in the middle ear has
been replacedbeen replaced with fluid (OME); or the function of the bonywith fluid (OME); or the function of the bony ossicles hasossicles has
been impaired (otosclerosis).been impaired (otosclerosis).
■ Hearing loss represents
impairment of the ability
to detect and perceive
■ Conductive hearing loss is
caused by disorders in
which auditory stimuli are
not transmitted through
the structures of the outer
and middle ears to the
sensory receptors in the
■ Sensorineural hearing
loss is caused by
disorders that affect the
inner ear, auditory nerve,
or auditory pathways.
Diseases of the Basal GangliaDiseases of the Basal Ganglia
The basal ganglia areThe basal ganglia are
made up of:made up of:
–– thethe corpus striatumcorpus striatum
(consisting of the(consisting of the caudatecaudate
nucleusnucleus and theand the
–– the inner and outerthe inner and outer
globus pallidusglobus pallidus
(pallidum, consisting of an(pallidum, consisting of an
internal and an externalinternal and an external
–– thethe subthalamicsubthalamic
nucleusnucleus; and; and
–– thethe substantia nigrasubstantia nigra
(pars reticulata [p. r.] and(pars reticulata [p. r.] and
pars compacta [p. c.]).pars compacta [p. c.]).
TheirTheir functionfunction is mainlyis mainly
to control movement into control movement in
conjunction with theconjunction with the
cerebellum,motor cortex,cerebellum,motor cortex,
corticospinal tracts, andcorticospinal tracts, and
motor nuclei in the brainmotor nuclei in the brain
Parkinson’s Disease Parkinson’s disease is a diseaseParkinson’s disease is a disease
of the substantia nigra (p. c.)of the substantia nigra (p. c.)
which via dopaminergic tractswhich via dopaminergic tracts
influences GABAergic cells in theinfluences GABAergic cells in the
corpus striatum. Thecorpus striatum. The causecause isis
frequently afrequently a hereditary dispositionhereditary disposition
that in middle to old age leads tothat in middle to old age leads to
degeneration of dopaminergicdegeneration of dopaminergic
neurons in the substantia nigra.neurons in the substantia nigra.
Further causes areFurther causes are traumatrauma (e.g.,(e.g.,
in boxers),in boxers), inflammationinflammation
(encephalitis),(encephalitis), impaired circulationimpaired circulation
(atherosclerosis),(atherosclerosis), tumorstumors andand
poisoningpoisoning (especially by CO,(especially by CO,
manganese, and 1-methyl-4-manganese, and 1-methyl-4-
[MPTP], which was once used as[MPTP], which was once used as
a substitute for heroin). The cella substitute for heroin). The cell
destruction probably occurs partlydestruction probably occurs partly
by apoptosis; superoxides areby apoptosis; superoxides are
thought to play a causal role. Forthought to play a causal role. For
symptoms to occur, over 70% ofsymptoms to occur, over 70% of
neurons in the substantia nigra (p.neurons in the substantia nigra (p.
c.) must have been destroyed.c.) must have been destroyed.
The loss of cells in the substantiaThe loss of cells in the substantia
nigra (p. c.) decreases thenigra (p. c.) decreases the
innervationinnervation of the striatum.of the striatum.
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