Pathophysiology of the Pathophysiology of the nervous system: violation of nervous system: violation of sensory, motor and trophic sensory, motor and trophic

function.function.

Actuality of the lectureActuality of the lecture The nervous system as a main regulatory system of an organism in this or The nervous system as a main regulatory system of an organism in this or

that measure participates in pathogenesis of each diseases. The earliest and that measure participates in pathogenesis of each diseases. The earliest and obligatory form of participation of the nervous system in pathology is obligatory 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-adrenal vomiting), 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 system At the same time during development of diseases the nervous system becomes the object of a defeat itself. It is defensive and adaptive the becomes the object of a defeat itself. It is defensive and adaptive the response of the damaged nervous system are reduced, and it becomes a response of the damaged nervous system are reduced, and it becomes a source of pathological, harmful to an organism reflexes. Itself graving and source of pathological, harmful to an organism reflexes. Itself graving and character of violations of nervous activity depend on localization of character 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 pathological Frequently there is a pain, which on the essence is typical pathological process, but at the same time has signal and adaptive significance. The process, but at the same time has signal and adaptive significance. The disturbance of nervous activity is always reflected in the function of internal disturbance of nervous activity is always reflected in the function of internal organs. organs.

The fundamental knowledges of the reasons and mechanisms of disorders The fundamental knowledges of the reasons and mechanisms of disorders motor, sensitive and trophic functions of the nervous system are necessary for motor, sensitive and trophic functions of the nervous system are necessary for understanding of pathogenesis nervous diseases, and also many symptoms understanding of pathogenesis nervous diseases, and also many symptoms of a damage of internal organs.of a damage of internal organs.

CONTENTCONTENT• Nervous System: Neurons Nervous System: Neurons • Division of the Nervous SystemDivision of the Nervous System • Pain: features of pain as a kind of Pain: features of pain as a kind of

sensitivity. Etiology and sensitivity. Etiology and pathogenesis of pain.pathogenesis of pain.

• Antinociceptive systemsAntinociceptive systems• Upper Motor NeuronsUpper Motor Neurons and Disorders and Disorders• Sensory LossSensory Loss• Spinal Cord InjuriesSpinal Cord Injuries• DysphasiaDysphasia• Diseases of the Basal GangliaDiseases of the Basal Ganglia

FunctionFunction of neurons of neurons A). Sensory input A). Sensory input  B). IntegrationB). Integration C). Response  C). Response  

A). Non nervous A). Non nervous or glial cellsor glial cells..1). Astrocytes1). Astrocytes2). Microglia2). Microglia3). Ependymal3). Ependymal4). Oliodendrocytes4). Oliodendrocytes5). Satellite cells5). Satellite cells6). 6). Schwann cellsSchwann cells form myelin sheaths  form myelin sheaths 

Types of cellsTypes of cells

Types of cellsTypes of cellsB). NeuronsB). Neurons 1). Structure 1). Structure II). ). cell body cell body oror soma soma -- endoplasmic endoplasmic

reticulum called thereticulum called the nissl body nissl body. . IIII). ). ProcessesProcesses or or tracts (nerves)tracts (nerves)

a).a). Dendrites: Dendrites: input regioninput regionb).b). Axon:Axon: Carries information away Carries information away c).c). Synaptic knobsSynaptic knobs or or Axonal Axonal terminalsterminals.. Releases Releases neurotransmitters.neurotransmitters.

2). 2). AxonsAxons a).a). myelin sheathmyelin sheath - - protects and protects and

electrically insulates fibers  conduct electrically insulates fibers  conduct nerve impulses faster than nerve impulses faster than nonmylenated fibers.nonmylenated fibers.

b).b). nodes of Ranvier nodes of Ranvier: :  spaces between the sheathsspaces between the sheathsThe action potential skips to the nodesThe action potential skips to the nodes

Nerve ImpulseNerve Impulse A). TermsA). Terms1). 1). Resting membrane PotentialResting membrane Potential: :  PolarizedPolarized2). 2). DepolarizationDepolarization: :  Change in ion concentrationChange in ion concentration3). 3). Hyperpolarization Hyperpolarization Change in ion concentration inside Change in ion concentration inside

becomes more negativebecomes more negative4). 4). Graded Potential Graded Potential Localized change in ion; subthresholdLocalized change in ion; subthreshold5). 5). Action Potential   Action Potential   Change in ion concentration that Change 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 potentialdepolarizes  depolarizes  

repolarizesrepolarizesundershoot phaseundershoot phase

UndershooUndershoott : : the K+ channels stay open the K+ channels stay open once resting potential is reached;once resting potential is reached;hyperpolarizing the cell.hyperpolarizing the cell.

Nerve Nerve ImpulseImpulseC). C). PropagationPropagation Cannot be depolarized again until the membrane has Cannot be depolarized again until the membrane has

reached resting potential. The action potential moves at a reached resting potential. The action potential moves at a constant velocity constant velocity

D). D). All or none phenomenonAll or none phenomenon Not all depolarizations result in action potentials The Not all depolarizations result in action potentials The

depolarization must reach the depolarization must reach the threshold pointthreshold point E). E). Refractory periodRefractory period absolute refractory periodabsolute refractory period cannot respond to another cannot respond to another

stimuli. stimuli. relative refractory period relative refractory period -- The threshold is higher The threshold is higher F). Impulse VelocityF). Impulse Velocity Strong stimuli result in more nerve impulses Not Strong stimuli result in more nerve impulses Not

stronger impulses or fasterstronger impulses or faster

SynapseSynapse – – junction that carries junction that carries information between neurons information between neurons 

A). TypesA). Types1). Electrical synapse: ions to cross junction1). Electrical synapse: ions to cross junction2). Chemical synapse2). Chemical synapse    neurotransmitters neurotransmitters   

                

B). Termination of neurotransmitterB). Termination of neurotransmitter 1). Degradation enzymes1). Degradation enzymes 2). Neurotransmitter reabsorbed2). Neurotransmitter reabsorbed 3). Diffusion of the neurotransmitter 3). Diffusion of the neurotransmitter 

Impulse Impulse 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 response.

(dendrites do not have action potentials)

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.  Induces hyperpolarization.

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

NeurotransmittersA). Acetylcholine (ACh) B). Biogenic Amines• 1). Dopamine• 2). Norepinephrine• 3). Epinephrine• 4). SerotoninC). Amino AcidsD). Peptides• 1). endorphinsE). Novel or

Miscellaneous

Division of the Nervous System

A). Central Nervous System: (CNS)

• Brain and Spinal Cord only  

B). Peripheral Nervous System

• Outside CNS1). Sensory or afferent

division:• Carries impulses to CNS 2). Motor or efferent

division• Carries impulses from the

CNS.I). Somatic Nervous System• voluntary  II). Autonomic Nervous

System• involuntary  • a.  Parasympathetic• b.  Sympathetic

The Sympathetic The Sympathetic Nervous SystemNervous System

The The first fibersfirst fibers of the sympathetic nerves, called the of 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 after Soon after leaving the spineleaving the spine, a preganglionic fiber , a preganglionic fiber joins joins other preganglionic fibersother preganglionic fibers to form an to form an autonomic autonomic ganglionganglion. .

At this point, the At this point, the preganglionic fiber synapsespreganglionic fiber synapses on the on the second nerve fiber of the systemsecond nerve fiber of the system, the , the postganglionic postganglionic fiberfiber, and , and releases acetylcholinereleases acetylcholine, which causes the , which causes the postganglionic fiber to fire an postganglionic fiber to fire an action potentialaction potential. .

From the From the autonomic gangliaautonomic ganglia, the postganglionic fiber , the postganglionic fiber travels to its travels to its target organtarget organ, the muscle or gland. , the muscle or gland.

The The sympathetic postganglionic fibersympathetic postganglionic fiber usually releases usually releases the the neurotransmitter norepinephrineneurotransmitter norepinephrine. . Target organ Target organ receptors for norepinephrinereceptors for norepinephrine are called are called adrenergic adrenergic receptorsreceptors..

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 or or leave the spinal leave the spinal cord from the sacral areacord from the sacral area. .

The The preganglionic fiberpreganglionic fiber of the of the PNSPNS is typically long and is typically long and travels travels to an autonomic ganglionto an autonomic ganglion located located near the target near the target organorgan. .

Preganglionic parasympathetic nervesPreganglionic parasympathetic nerves release release acetylcholineacetylcholine that that then stimulates the postganglionic then stimulates the postganglionic fiberfiber. .

The The parasympathetic postganglionic fiberparasympathetic postganglionic fiber then travels a then travels a short distance short distance 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 and for sympathetic and parasympathetic fibersparasympathetic fibers are called are called nicotinic receptorsnicotinic receptors. .

Postganglionic acetylcholine receptorsPostganglionic acetylcholine receptors are called are called muscarinic receptorsmuscarinic receptors. These names relate to the . These names relate to the experimental stimulation of the receptors by experimental stimulation of the receptors by nicotinenicotine and and muscarinemuscarine (a mushroom poison). (a mushroom poison).

Functions of the Sympathetic and Functions of the Sympathetic and Parasympathetic NervesParasympathetic Nerves

The The sympathetic nervous systemsympathetic nervous system innervates the innervates the heartheart, , causing an causing an increase in heart rateincrease in heart rate and and strength of contractionstrength of contraction. .

Sympathetic nervesSympathetic nerves innervate innervate all large and small arteriesall large and small arteries and and veinsveins, causing , causing constriction of all vessels constriction of all vessels except the except the arterioles supplying skeletal musclearterioles supplying skeletal muscle. .

Sympathetic nervesSympathetic nerves innervate the innervate the smooth muscle of the smooth muscle of the gutgut, causing , causing decreased motilitydecreased motility, and the , and the smooth muscle of smooth muscle of the respiratory tractthe respiratory tract, causing , causing bronchial relaxationbronchial relaxation and and decreased bronchial secretionsdecreased bronchial secretions. .

Sympathetic stimulationSympathetic stimulation affects the affects the liverliver, , stimulates stimulates secretions of the secretions of the sweat glandssweat glands, and is responsible for , and is responsible for ejaculation during male orgasmejaculation during male orgasm..

Parasympathetic fibersParasympathetic fibers innervate the innervate the heartheart, , slowing the slowing the heart rateheart rate, and the , and the gutgut, causing , causing increased motilityincreased motility. .

Parasympathetic nervesParasympathetic nerves innervate innervate bronchial smooth bronchial smooth musclemuscle, causing , causing airway constrictionairway constriction, and the , and the genitourinary genitourinary tracttract, causing , causing erection in the maleerection in the male..

The Autonomic Nervous SystemStructure 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 increased

Small Intestine Motility reduced Digestion increased

Large Intestine Motility reduced Secretions and motility increased

Liver Increased conversion of glycogen to glucose

---

Kidney Decreased urine secretion Increased urine secretion

Adrenal medulla Norepinephrine and epinephrine secreted

---

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: touch, touch, temperature,temperature, pain, pain, body positionbody position. .

Stimulation of receptorsStimulation of receptors on regions of the body wall is on regions of the body wall is required torequired to initiate the sensory response.initiate the sensory response.

■ ■ The system is organized into The system is organized into dermatomesdermatomes, with each, with each segment supplied by a segment supplied by a single dorsal root ganglionsingle dorsal root ganglion that that sequentially relays the sensory information tosequentially relays the sensory information to the the spinal cord, the thalamus, and the sensoryspinal cord, the thalamus, and the sensory cortexcortex..

■ ■ Two pathwaysTwo pathways carry sensory information throughcarry sensory information through the the CNSCNS. The . The discriminative pathwaydiscriminative pathway crosses in the crosses in the medulla and relays touch and body position. Themedulla and relays touch and body position. The anterolateral pathwayanterolateral pathway crosses in the spinal cord crosses in the spinal cord and and relays temperature and pain sensation fromrelays temperature and pain sensation from the the 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 experience:

(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 Sensitivity1. 1. PainfulPainful2. 2. TemperatureTemperature3. 3. TactileTactile4. 4. ProprioceptiveProprioceptive

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 organism which arise owing to action on an organism painfulpainful ( (nociceptivenociceptive) ) irritantirritant oror weakeningweakening ofof antipainful antipainful ((antinociceptiveantinociceptive) ) systemsystem

PainPain is an “unpleasant sensory and is an “unpleasant sensory and emotional experience associatedemotional experience associated with with potential tissue damage, or described in potential tissue damage, or described in terms ofterms of such damage.”such damage.”

CLASSIFICATION OF PAIN• Physiological pain• Pathological pain• Acute pain• Chronical pain

MEDIATORS OF PAINMEDIATORS OF PAIN• Substanse Р• Glutamic acid• Cholecystokinin• Neurotensin

TYPES OF PAINTYPES OF PAIN Pain can be classified according to location, site of referral, and duration. 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 tissues.

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 responses.

Chronic pain is persistent pain that is accompanied by loss of appetite, sleep disturbances, depression, and other debilitating responses.

PAIN SENSATION■ 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 paleospinothalamic tract.

■ 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 classical views of pain transmission and pain transmission and pain modulationpain modulation (a). (a). Classical pain Classical pain transmission transmission pathwaypathway. .

(b):(b): Normal painNormal pain. . Under basal Under basal conditions, pain is not conditions, pain is not modulated by glia. modulated by glia.

(c)(c) Pain Pain facilitation:facilitation: classical classical view. In response to view. In response to intense and/or intense and/or prolonged barrages prolonged barrages of incoming “pain” of incoming “pain” signals, the PTNs signals, the PTNs become sensitized become sensitized and over-respond to and over-respond to subsequent incoming subsequent incoming signals signals

(d)(d) Pain Pain facilitation:facilitation: new new view. Here, glial view. Here, glial activation is activation is conceptualized as a conceptualized as a driving force for driving force for creating and creating and maintaining pain maintaining pain facilitation. facilitation.

Pain TheoriesPain Theories Traditionally, two theories have been offered to Traditionally, two theories have been offered to

explain theexplain the physiologic basis for the pain experience. physiologic basis for the pain experience. The The firstfirst, , specificityspecificity theorytheory, regards pain as a , regards pain as a

separate sensory modality evoked byseparate sensory modality evoked by the activity of the activity of specific receptors that transmit information tospecific receptors that transmit information to pain pain centers or regions in the forebrain where pain is centers or regions in the forebrain where pain is experienced.experienced.

The The secondsecond theory includes a group of theories theory includes a group of theories collectivelycollectively referred to as referred to as pattern theorypattern theory. It proposes . It proposes that that pain receptorspain receptors share endings or pathways with share endings or pathways with other sensory modalitiesother sensory 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, was modification of specificity theory, was proposed proposed

by Melzack and Wall in 1965 to meet the by Melzack and Wall in 1965 to meet the challengeschallenges presented by the pattern theories. This presented by the pattern theories. This theory postulated thetheory postulated the presence of neural gating presence of neural gating mechanisms at the mechanisms at the segmental spinalsegmental spinal cord level to cord level to account for interactions between pain and account for interactions between pain and othersensory modalitiesothersensory modalities. .

According to the According to the gate control theorygate control theory, the , the internuncialinternuncial neuronsneurons involved in the gating involved in the gating mechanism mechanism 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 touch touch fibersfibers has the has the potential for blocking the potential for blocking the transmission oftransmission of impulsesimpulses from the from the small-diameter small-diameter myelinated and unmyelinatedmyelinated and unmyelinated pain fiberspain fibers..

NNeuromatrix euromatrix TTheoryheory 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 pain experience.

The neuromatrix theory proposes that the brain contains a widely distributed neural network, called the body-self neuromatrix, that contains somatosensory, limbic, and somatosensory, limbic, and thalamocortical componentsthalamocortical 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: somatosensory; 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.

PAIN• 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 postganglionic neurons.

• 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 spontaneously active.

• 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 neuropathic pain.

PainPain Free nerve endingsFree nerve endings of of

unmyelinated C fibers and small-unmyelinated C fibers and small-diameter myelinated Adiameter myelinated Aδδ fibers in fibers in the skin convey sensory information the skin convey sensory information in response to in response to chemical, thermal, chemical, thermal, and mechanical stimuliand mechanical stimuli. .

Intense stimulationIntense stimulation of these nerve of these nerve endings endings evokes the sensation of evokes the sensation of painpain. .

In contrast to skin, most deep In contrast to skin, most deep tissues are relatively insensitive to tissues are relatively insensitive to chemical or noxious stimuli. chemical or noxious stimuli.

However, inflammatory conditions However, inflammatory conditions can sensitize sensory afferents from can sensitize sensory afferents from deep tissues to evoke pain on deep tissues to evoke pain on mechanical stimulation. This mechanical stimulation. This sensitization appears to be sensitization appears to be mediated bymediated by bradykinin, bradykinin, prostaglandins, and leukotrienesprostaglandins, and leukotrienes released during the inflammatory released during the inflammatory response. response.

Information from Information from primary afferent primary afferent fibersfibers is relayed is relayed via sensory gangliavia sensory ganglia to the to the dorsal horn of the spinal corddorsal horn of the spinal cord and then to the and then to the contralateral contralateral spinothalamic tractspinothalamic tract, which connects , which connects to to thalamic neuronsthalamic neurons that project to that project to the the somatosensory cortexsomatosensory cortex..

Primary pain pathways

NociceptiveNociceptivestimulistimuli

Somesthetic association cortexSomesthetic association cortex(perception and meaning)(perception and meaning)

Limbic cortexLimbic cortex(emotional experience)(emotional experience)

PontinePontinenoradrenergic neuronsnoradrenergic neurons

Primary somesthetic cortexPrimary somesthetic cortex(discrimination: location and intensity)(discrimination: location and intensity)

Medullary raphe nucleusMedullary raphe nucleus

Thalamus (sensation)Thalamus (sensation)Somesthetic nucleiSomesthetic nuclei

Spinal cord and dorsal hornSpinal cord and dorsal hornpain modulating circuitspain modulating circuits

Periaqueductal gray (PAG)Periaqueductal gray (PAG)(endogenous analgesic center)(endogenous analgesic center)

Medullary NRMMedullary NRM

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Characteristics of Characteristics of Acute and Chronic PainAcute and Chronic Pain

Characteristic Acute Pain Chronic Pain

OnsetRecent Continuous or

intermittent

Duration Short duration (<6 months) 6 months or more

Autonomic responses

Consistent with sympathetic fight-orflight response*

Increased heart rateIncreased stroke volumeIncreased blood pressureIncreased pupillary dilationIncreased muscle tensionDecreased gut motilityDecreased salivary flow (dry

mouth)

Absence of autonomicresponses

Psychological component

Associated anxiety Increased irritabilityAssociated depressionSomatic preoccupationWithdrawal from outside

interestsDecreased strength of

relationships

Other types of responseDecreased sleepDecreased libidoAppetite changes

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 SensitivityAlterations in Pain Sensitivity

Hypersensitivity (i.e., hyperesthesia) or increased painfulness (i.e., hyperalgesia)

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 localized ischemia.

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 SensitivityAlterations 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., hypalgesia).

• 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.

• 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 stimulation.

CHRONICAL PAINFULCHRONICAL PAINFUL SYNDROMESSYNDROMES

Phantom pain

Causalgia

Neuralgia

Eccentric pain

Projectional pain

NeuralgiaNeuralgia NeuralgiaNeuralgia is characterized by severe, is characterized by severe,

brief, often repetitive attacksbrief, often repetitive attacks of lightning-of lightning-like or throbbing pain. It occurs along the like or throbbing pain. It occurs along the distributiondistribution of a spinal or cranial nerve and of a spinal or cranial nerve and usually is precipitatedusually is precipitated by stimulation of the by stimulation of the cutaneous region supplied by that nerve.cutaneous region supplied by that nerve.

Trigeminal Neuralgia.Trigeminal Neuralgia. Trigeminal neuralgia, or Trigeminal neuralgia, or tic douloureuxtic douloureux,, is one of is one of the most common and the most common and severe neuralgias. It is severe neuralgias. It is manifestedmanifested by by facial ticsfacial tics or or grimacesgrimaces and and characterized by characterized by stabbing,stabbing, paroxysmal paroxysmal attacks of pain that attacks of pain that usually are limited to the usually are limited to the unilateralunilateral sensory sensory distribution of one or distribution of one or more branches of themore branches of the trigeminal nerve, most trigeminal nerve, most often the maxillary or often the maxillary or mandibular divisions.mandibular divisions.

Postherpetic Neuralgia.Postherpetic Neuralgia.

Postherpetic pain is pain Postherpetic pain is pain that persiststhat persists as a as a complication of herpes complication of herpes zoster or shingles. It zoster or shingles. It describes thedescribes the presence of presence of pain more than 1 month pain more than 1 month after the onset of the after the onset of the acuteacute attack. attack. Postherpetic neuralgiaPostherpetic neuralgia develops in from 10% to develops in from 10% to 70% of70% of patients with patients with shingles; the risk shingles; the risk increases with age. increases with age. The pain ofThe pain of postherpetic postherpetic neuralgia occurs in the neuralgia occurs in the areas of innervation of areas of innervation of thethe infected gangliainfected ganglia. . During the acute attack of During the acute attack of herpes zosterherpes zoster, the, the reactivated virus travels reactivated virus travels from the ganglia to the from the ganglia to the skin of the correspondingskin of the corresponding dermatomes, causing dermatomes, causing localized vesicular localized vesicular eruptioneruption and hyperpathia and hyperpathia ((i.e.i.e., abnormally , abnormally exaggerated subjective exaggerated subjective responseresponse to pain). to pain).

Postherpetic Neuralgia

Phantom Limb PainPhantom Limb PainPhantom Limb PainPhantom 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 tingling, heat and cold, or heaviness,cold, or heaviness, followed by followed by burning, cramping, or shooting burning, cramping, or shooting painpain. 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 catecholamines.

• 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 has been accomplished by the use of sympathetic blocks, TENS of the large myelinated afferents innervating the area, hypnosis, and relaxation training.

Antinociceptive systemsAntinociceptive systems NeuronalNeuronal opiate systemopiate system – – metmet- - and and

leuencephalinleuencephalin NeuronalNeuronal unopiate systemunopiate system – – noradrenalinnoradrenalin, ,

serotoninserotonin, , dopaminedopamine HormonalHormonal opiate systemopiate system – – hormoneshormones of of

adenohypophysisadenohypophysis HormonalHormonal unopiate systemunopiate system – – vasopressinvasopressin

Hormonal unopiate systemHormonal unopiate system

1. 1. Adrenocorticotropic hormoneAdrenocorticotropic hormone 2. 2. MelanostimulatingMelanostimulating hormoneshormones 3. 3. β β --LipotropicLipotropic hormonehormone 4. 4. LargeLarge endorphinesendorphines:: kitorphinkitorphin ββ--kosomorphinkosomorphin dinorphindinorphin

1.1. Opening of abscessOpening of abscess2.2. Reposition ofReposition of

fragmentsfragments3.3. Splintation of extremitySplintation of extremity4.4. Section of scarsSection of scars5.5. DesympathizationDesympathization6.6. GangliectomyGangliectomy

1.1. AcupunctureAcupuncture2.2. ElectroacupunctureElectroacupuncture3.3. LaseropunctureLaseropuncture4.4. ElectrostimulationElectrostimulation5.5. ElectrophoresisElectrophoresis6.6. UltrasoundUltrasound7.7. Magnetico-laserMagnetico-laser therapytherapy8.8. MassageMassage9.9. Manual Manual therapytherapy

METHODS OF ANAESTIZATION

PsycologicalPsycological PhysicalPhysical PharmacologicPharmacologic

alal SurgicalSurgical NeurosurgicalNeurosurgical

1. 1. ConversationConversation 2. 2. RelaxationRelaxation 3. 3. HypnosisHypnosis 4. 4. AutotrainingAutotraining 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

AnatomyAnatomy The The motor cortexmotor cortex is the is the

region from which region from which movements can be elicited movements can be elicited by electrical stimuli (Figure). by electrical stimuli (Figure).

This includes: the primary motor area

(Brodmann area 4), premotor cortex (area 6), supplementary motor

cortex (medial portions of 6), 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 muscles.

► Cortical motor neuronsCortical motor neurons contribute axons that contribute axons that converge in the corona radiata and descend in converge in the corona radiata and descend in the the posterior limb of the internal capsule, posterior limb of the internal capsule, cerebral peduncles, ventral pons, and medullacerebral peduncles, ventral pons, and medulla. . These fibers constitute the These fibers constitute the corticospinalcorticospinal and and corticobulbar tractscorticobulbar tracts and together are and together are known known as upper motor neuron fibersas upper motor neuron fibers. As they . As they descend through the diencephalon and descend through the diencephalon and brainstem, fibers separate to innervate brainstem, fibers separate to innervate extrapyramidal and cranial nerve motor nuclei. extrapyramidal and cranial nerve motor nuclei. The lower brainstem motor neurons receive The lower brainstem motor neurons receive input from crossed and uncrossed corticobulbar input from crossed and uncrossed corticobulbar fibers, although neurons that innervate lower fibers, although neurons that innervate lower facial muscles receive primarily crossed fibers.facial muscles receive primarily crossed fibers.

► In the ventral medulla, the remaining In the ventral medulla, the remaining corticospinal fibers course in a tract that is corticospinal fibers course in a tract that is pyramidal in shape in cross section—thus, the pyramidal in shape in cross section—thus, the name name pyramidal tract.pyramidal tract. At the At the lower end of the lower end of the medullamedulla, most fibers decussate, although the , most fibers decussate, although the proportion of crossed and uncrossed fibers varies proportion of crossed and uncrossed fibers varies somewhat between individuals. The bulk of somewhat between individuals. The bulk of these fibers descend as the lateral corticospinal these fibers descend as the lateral corticospinal tract of the spinal cord.tract of the spinal cord.

► Different groups of neurons in the cortex control Different groups of neurons in the cortex control muscle groups of the contralateral face, arm, muscle groups of the contralateral face, arm, and leg. Neurons near the ventral end of the and leg. Neurons near the ventral end of the central sulcus control muscles of the face, central sulcus control muscles of the face, whereas neurons on the medial surface of the whereas neurons on the medial surface of the hemisphere control leg muscles. Because the hemisphere control leg muscles. Because the movements of the face, tongue, and hand are movements of the face, tongue, and hand are complex in humans, a large share of the motor complex in humans, a large share of the motor cortex is devoted to their controlcortex is devoted to their control. A somatotopic . A somatotopic organization is also apparent in the lateral organization is also apparent in the lateral corticospinal tract of the cervical cord, where corticospinal tract of the cervical cord, where fibers to motor neurons that control leg muscles fibers to motor neurons that control leg muscles lie laterally and fibers to cervical motor neurons lie laterally and fibers to cervical motor neurons lie medially.lie medially.

Upper and Lower motoneurons innervate the skeletal Upper and Lower motoneurons innervate the skeletal musclesmuscles a and are essential for motor function.nd are essential for motor function.

• Amyotrophic lateral sclerosis (ALS)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 Upper and Lower motoneurons innervate the skeletal musclesmuscles a and are essential for motor function.nd 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.

ETIOPATHOPHYSIOLOGY, PATHOLOGY • 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 SCLEROSIS)

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 sclerosisCytoplasmic ultrastructural abnormalities (cytoskeleton is affected Cytoplasmic ultrastructural abnormalities (cytoskeleton is affected

early!):early!): 1) in proximal motor axons - strongly argentophilic 1) in proximal motor axons - strongly argentophilic SPHEROIDS SPHEROIDS

(accumulated (accumulated neurofilament bundlesneurofilament bundles that may contain other cytoplasmic that may contain other cytoplasmic structures, such as mitochondria). structures, such as mitochondria). some patients have mutations in some patients have mutations in neurofilament heavy chain subunit neurofilament heavy chain subunit (22q).(22q). abnormal neurofilaments interfere with axonal transport, resulting in abnormal neurofilaments interfere with axonal transport, resulting in failure to maintain axonal structure and transport of macromolecules failure 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 bodies Bunina bodies - tiny round eosinophilic structures. - tiny round eosinophilic structures. 3) 3) Lewy body-like eosinophilic inclusions Lewy body-like eosinophilic inclusions (immunoreactive to (immunoreactive to

neurofilaments, ubiquitin neurofilaments, 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 in Number of abnormalities in GLUTAMATEGLUTAMATE metabolism have been metabolism have been identified in ALS (incl. alterations in tissue glutamate levels, transporter identified 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 have 60% patients have large decrease in GLUTAMATE TRANSPORT large decrease in GLUTAMATE TRANSPORT activity*activity* in motor cortex and spinal cord (but not in other regions of in 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 → excitotoxicity. excitotoxicity.

*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).

DemyelinationDemyelination In myelinated nerves, the axon between two nodes of Ranvier (internodal In myelinated nerves, the axon between two nodes of Ranvier (internodal

segment) is surrounded by a segment) 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” propagation saltatory conduction of the action potentials, i.e., the “jumping” propagation of excitation from one nodal constriction (R1) to the next (R2). The of 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 the depolarization of the second node (R2) is completely dependent on the current from the first node (R1). However, the current is usually so strong current 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 the Nevertheless, on the way along the internodal segment the amplitude of the current will diminish. First of all, the membrane in the internodal segment current will diminish. First of all, the membrane in the internodal segment must change its polarity, i.e., the must change its polarity, i.e., the membrane capacitance membrane capacitance must be must be discharged, for which a current is needed. Secondly, current can also discharged, for which a current is needed. Secondly, current can also escape through individual escape through individual ionic channels ionic channels in the axonal membrane (orange in the axonal membrane (orange arrow). However, myelination of the internodal segment causes the arrow). However, myelination of the internodal segment causes the membrane resistance (Rm) to be elevated and the capacity (Cm) of the membrane resistance (Rm) to be elevated and the capacity (Cm) of the membrane condensor to be reduced.membrane condensor to be reduced.

The The resistance resistance of the axonal membrane of the internodal segment is very of the axonal membrane of the internodal segment is very high because of the low density of ionic channels there. Furthermore, the high because of the low density of ionic channels there. Furthermore, the perimembranous space is insulated by a layer of fat from the free perimembranous space is insulated by a layer of fat from the free extracellular space. The low extracellular space. The low capacitance capacitance of the condensor is due to the of the condensor is due to the large distance between the interior of the axon and the free extracellular large 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 between space as well as the low polarity of the fatty material in the space between them.them.

Demyelination Demyelination can be can be caused by degenerative, caused by degenerative, toxic, or inflammatory toxic, or inflammatory damage to the nerves, or damage to the nerves, or by a deficiency of by a deficiency of vitamins B6 or B12. vitamins B6 or B12. If this happens, Rm will If this happens, Rm will be reduced and Cm be reduced and Cm raised in the internodal raised in the internodal segment. segment. As a result, more current As a result, more current will be required to will be required to change the polarity of change the polarity of the internodal segment the internodal segment and, through opening up and, through opening up the ionic channels, large the ionic channels, large losses of current may losses of current may occur.occur.

Multiple SclerosisMultiple Sclerosis

• Multiple sclerosisMultiple 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 an is 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, jerky patients develop involuntary, rapid, jerky movements (movements (choreachorea) and slow writhing ) and slow writhing movements of the proximal limbs and trunk movements of the proximal limbs and trunk ((athetosisathetosis). ).

When disease onset occurs earlier in life, When disease onset occurs earlier in life, patients develop signs of parkinsonism with patients develop signs of parkinsonism with tremor (cogwheeling) and stiffness. The tremor (cogwheeling) and stiffness. The spiny GABAergic neuronsspiny GABAergic neurons of the striatum of the striatum preferentially degenerate, resulting in a net preferentially degenerate, resulting in a net decrease in GABAergic output from the decrease in GABAergic output from the striatum. This contributes to the striatum. This contributes to the development of chorea and athetosis. development of chorea and athetosis.

Dopamine Dopamine antagonists, which block antagonists, which block inhibition of remaining striatal neurons by inhibition of remaining striatal neurons by dopaminergic striatal fibers, reduce the dopaminergic striatal fibers, reduce the involuntary movements. Neurons in deep involuntary movements. Neurons in deep layers of the cerebral cortex also layers of the cerebral cortex also degenerate early in the disease, and later degenerate early in the disease, and later this extends to other brain regions, including this extends to other brain regions, including the hippocampus and hypothalamus. Thus, the hippocampus and hypothalamus. Thus, the disease is characterized by cognitive the disease is characterized by cognitive defects and psychiatric disturbances in defects and psychiatric disturbances in addition to the movement disorder.addition to the movement disorder.

HUNTINGTON DISEASEHUNTINGTON DISEASEClassical familial, Classical familial, genetic diseasegenetic diseaseProgressive Progressive motor loss and motor loss and dementiadementia““chorea”, i.e. chorea”, i.e. “jerky” “jerky” movementsmovementsProgressive, fatalProgressive, fatalAtrophy of basal Atrophy of basal ganglia, i.e., ganglia, i.e., corpus striatumcorpus striatum Cortical (basal ganglia) atrophyCortical (basal ganglia) atrophy

Ventricular enlargementVentricular enlargement

CNS DEGENERATIVE CNS DEGENERATIVE DISEASESDISEASES

•SPINOCEREBELLAR SPINOCEREBELLAR DEGENERATIONS DEGENERATIONS (ATAXIAS)(ATAXIAS)– Spinocerebellar ataxiasSpinocerebellar ataxias– Friedrich AtaxiaFriedrich Ataxia– Ataxia-TelangiectasiaAtaxia-Telangiectasia

SPINOCEREBELLAR DEGENERATIONSSPINOCEREBELLAR DEGENERATIONS

Cerebellar cortexCerebellar cortex Spinal cordSpinal cord Peripheral nervesPeripheral nerves

FEATURES:FEATURES:

•ATAXIAATAXIA (loss of extremity muscle (loss of extremity muscle coordination)coordination)

• SPASTICITYSPASTICITY• NEUROPATHIESNEUROPATHIES

ACQUIRED ACQUIRED TOXIC/METABOLICTOXIC/METABOLIC

CNS DISEASESCNS DISEASES VitaminVitamin B1B1 deficiency (Wernicke-Korsakoff)deficiency (Wernicke-Korsakoff) Vitamin Vitamin B12 B12 deficiency (vibratory sense)deficiency (vibratory sense) Diabetes Diabetes Increased/Decreased GLUCOSEIncreased/Decreased GLUCOSE Hepatic FailureHepatic Failure (NH4+)(NH4+) CO CO (Cortex, hippocampus, Purkinje cells)(Cortex, hippocampus, Purkinje cells) CH3-OHCH3-OH, Methanol (Retinal ganglion cells), Methanol (Retinal ganglion cells) CH3-CH2-OH CH3-CH2-OH (acute/chronic, direct/nutrit’l)(acute/chronic, direct/nutrit’l) RadiationRadiation (Brain MOST resistant to Rad. Rx.)(Brain MOST resistant to Rad. Rx.) Chemo Chemo (Methotrexate + Radiation)(Methotrexate + Radiation)

Discriminative SensationDiscriminative Sensation Primary sensory cortex provides Primary sensory cortex provides

awareness of somatosensory information awareness of somatosensory information and the ability to make sensory and the ability to make sensory discriminations. discriminations.

Touch, pain, temperature, and vibration Touch, pain, temperature, and vibration sense are considered the primary sense are considered the primary modalities of sensation and are relatively modalities of sensation and are relatively preserved in patients with damage to preserved in patients with damage to sensory cortex or its projections from the sensory cortex or its projections from the thalamus. thalamus.

In contrast, complex tasks that require In contrast, complex tasks that require integration of multiple somatosensory integration of multiple somatosensory stimuli and of somatosensory stimuli with stimuli and of somatosensory stimuli with auditory or visual information are impaired. auditory or visual information are impaired.

These include the ability to distinguish These include the ability to distinguish two two pointspoints from one when touched on the skin from one when touched on the skin ((two-point discriminationtwo-point discrimination), localize tactile ), localize tactile stimuli, perceive the position of body parts stimuli, perceive the position of body parts in space, recognize letters or numbers in space, recognize letters or numbers drawn on the skin (drawn on the skin (graphesthesiagraphesthesia), and ), and identify objects by their shape, size, and identify objects by their shape, size, and texture (texture (stereognosisstereognosis).).

Anatomy of Sensory LossAnatomy of Sensory LossThe 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 (polyneuropathy). Sensory symptoms and deficits may be restricted to the distribution of a single peripheral nerve (mononeuropathy) or two or more peripheral nerves (mononeuropathy multiplex). Symptoms limited to a dermatome indicate a spinal root lesion (radiculopathy).

Alterations in Motor Responses and Alterations in Motor Responses and MovementMovement

Abnormal motor responses include inappropriate or absent Abnormal motor responses include inappropriate or absent movements in response to painful stimuli. Brainstem movements in response to painful stimuli. Brainstem reflexes such as sucking and grasping responses will occur reflexes such as sucking and grasping responses will occur if higher brain centers have been damaged. if higher brain centers have been damaged.

Flexion and rigidity of limbs also are motor responses Flexion and rigidity of limbs also are motor responses indicative of brain damage. indicative of brain damage.

Muscle conditionsMuscle conditions that indicate abnormal brain function that indicate abnormal brain function include include hyperkinesia hyperkinesia ((excessive muscle movementsexcessive muscle movements), ), hypokinesiahypokinesia ( (decreased muscle movementsdecreased muscle movements), ), paresis paresis ((muscle weaknessmuscle weakness), and ), and paralysisparalysis ( (loss of motor functionloss of motor function). ).

Specific loss of cerebral cortex functioning, but no loss of Specific loss of cerebral cortex functioning, but no loss of brainstem function, results in a particular body posture brainstem function, results in a particular body posture called called flexor posturingflexor posturing. .

Flexor posturingFlexor posturing is characterized by flexion of the upper is characterized by flexion of the upper extremities at the elbows and external rotation and extremities at the elbows and external rotation and extension of the lower extremities. This posture extension of the lower extremities. This posture may be may be unilateral or bilateralunilateral or bilateral. Extensor posturing occurs with severe . Extensor posturing occurs with severe injury to higher brain centers and the brainstem and is injury to higher brain centers and the brainstem and is characterized by characterized by rigid extension of the limbs and neckrigid extension of the limbs and neck..

Brown-Séquard syndrome• 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 syndrome).

• 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 upper arms.

SPINAL CORD INJURIESSPINAL CORD INJURIESCAUSES:CAUSES:

TRAUMATRAUMA FALLSFALLS GSWGSW TUMORSTUMORS

TYPES:TYPES:

CONCUSSIONCONCUSSION COMPRESSIONCOMPRESSION CONTUSION & CONTUSION &

TRANSECTIONTRANSECTION LACERATIONLACERATION HEMORRHAGEHEMORRHAGE (HEMATOMYALIA)(HEMATOMYALIA) COMPRESSION OF COMPRESSION OF

BLOOD SUPPLY TO THE BLOOD SUPPLY TO THE CORDCORD

Injury Level

Segmental Sensorimotor Function Dressing, Eating Elimination Mobility

C1 Little or no sensation or control of head and neck; no diaphragm control; requires continuous ventilation

Dependent Dependent Limited. Voice or sip-n-puff controlled electric wheelchair

C2 to C3

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; diaphragm movement

Dependent; may be able to eat with adaptive sling

Dependent Limited to voice, mouth, head, chin, or shoulder-controlled electric wheelchair

C5 Full head and neck control; shoulder strength; elbow flexion

Independent with assistance

Maximal assistance Electric or modified manual wheel chair, needs transfer assistance

C6 Fully innervated shoulder; wrist extension or dorsiflexion

Independent or with minimal assistance

Independent or with minimal assistance

Independent in transfers and wheelchair

C7 to C8

Full elbow extension; wrist plantar flexion; some finger control

Independent Independent Independent; manual wheelchair

T1 to T5

Full hand and finger control; use of intercostal and thoracic muscles

Independent Independent Independent; manual wheelchair

T6 to T10

Abdominal muscle control, partial to good balance with trunk muscles

Independent Independent Independent; manual wheelchair

T11 to L5

Hip flexors, hip abductors (L1–3); knee extension (L2–4); knee flexion and ankle dorsiflexion (L4–5)

Independent Independent Short distance to full ambulation with assistance

S1 to S5

Full leg, foot, and ankle control; innervation of perineal muscles for bowel, bladder, and sexual function (S2–4)

Independent Normal to impaired bowel and bladder

function

Ambulate independently with or without assistance

Functional Abilities by Level of Cord Injury

CLINICAL EFFECTS OF SCICLINICAL EFFECTS OF SCI

• SPINAL SHOCK

• REFLEX ACTIVITY

• WHIPLASH INJURY

• HERNIATED NUCLEUS PULPOSUS

SPINAL SHOCKSPINAL SHOCK• IMMEDIATE FLACCID PARALYSIS & SENSORY LOSS

BELOW THE LEVEL OF LESION

• PRIAPISM

• BULBOCAVERNOUS REFLEX IS LOST BUT REUTRNS AFTER A FEW HRS

• OTHER REFLEXES REMAIN ABSENT

• 3-6 WKS

AUTONOMIC DISTURBANCES:AUTONOMIC DISTURBANCES: •SWEATING IS ABOLISHED

BELOW THE LEVEL OF INJURY•URINE & FECES RETAINED•GASTRIC ATONY•ORTHOSTATIC HYPOTENSION•SLOW, & STEADY PULSE

REFLEX ACTIVITYREFLEX ACTIVITY• REPLACE SPINAL SHOCK AFTER 2-3

WEEKS IF LUMBO-SACRAL SEGMENTS ARE UNDAMAGED

• 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

PLANTAR STIMULATION

ParalysisParalysis ParalysisParalysis is the loss of sensory and voluntary motor is the loss of sensory and voluntary motor

function. With spinal cord transection, paralysis is function. With spinal cord transection, paralysis is permanent. permanent.

Paralysis Paralysis of the of the upper and lower extremitiesupper and lower extremities occurs with occurs with transection of the cord at level C6 or higher and is called transection of the cord at level C6 or higher and is called quadriplegiaquadriplegia. .

ParalysisParalysis of the lower half of the body occurs with of the lower half of the body occurs with transection of the cord below C6 and is called transection of the cord below C6 and is called paraplegiaparaplegia. .

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 is may occur even when the cord is not transected, as a result of the destruction of the not transected, as a result of the destruction of the nerves following cord nerves following cord hemorrhage and swellinghemorrhage and swelling. .

In addition, demyelination of the axons in the cord can In addition, demyelination of the axons in the cord can lead to clinically complete lesions, even though the lead 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 of of the axons most likely occurs as part of the inflammatory response to cord injury.the inflammatory response to cord injury.

Clinical Manifestations

of Paralysis

• Loss of sensation, motor control, and reflexes below the level of injury, and up to two levels above, will occur. Body temperature will reflect ambient temperature, and blood pressure will be reduced.

• The pulse rate is often normal, with low blood pressure.

Complications• 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 transection.

• 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.

DysphasiaDysphasia 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 often Dysphasia usually results from cerebral hypoxia, which is often associated with a stroke but can result from trauma or infection. Brain associated with a stroke but can result from trauma or infection. Brain damage leading to dysphasia usually involves the left cerebral damage leading to dysphasia usually involves the left cerebral hemisphere.hemisphere.

Broca's dysphasia results from damage to Broca's area in the frontal results from damage to Broca's area in the frontal lobe. Persons with Broca's dysphasia will understand language, but lobe. Persons with Broca's dysphasia will understand language, but their ability to meaningfully express words in speech or writing will be their 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 the results from damage to Wernicke's area in the left temporal lobe. With Wernicke's dysphasia, verbal expression of left temporal lobe. With Wernicke's dysphasia, verbal expression of language is intact, but meaningful understanding of spoken or written language 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 inability is 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 from auditory, tactile, or related to taste or smell. Agnosia develops from damage to a particular primary or associative sensory area in the damage 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 pupilsdilated pupils usually seen with severe hypoxia.

• Fixed pupils are typically seen with barbiturate overdose.

• Brainstem injury presents with pupils fixed bilaterally in the midposition.

DISORDERS OF THE RETINAL DISORDERS OF THE RETINAL BLOOD SUPPLYBLOOD SUPPLY

■ 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 and cones.

■ Central retinal occlusion interrupts blood flow to the inner retina and results in unilateral blindness.

■ The retinopathies, which are disorders of the retinal vessels, interrupt blood flow to the visual receptors, leading to visual impairment.

■ Retinal detachment separates the visual receptors from the choroid, which provides their major blood supply.

Fundus of the eye as seen in retinal examination with an ophthalmoscope: (left) normal fundus; (middle) diabetic retinopathy—combination of microaneurysms, deep hemorrhages, and hard exudates of background retinopathy; (right) hypertensive retinopathy with purulent exudates. Some exudates are scattered, while others radiate from the fovea to form a macular star.

DISORDERS OF DISORDERS OF THE MIDDLE EARTHE MIDDLE EAR

■ ■ The middle ear is a small air-filled The middle ear is a small air-filled compartment incompartment in the temporal bone. It the temporal bone. It is separated from the outer earis separated from the outer ear by the by the tympanic membrane, contains tiny tympanic membrane, contains tiny bony ossiclesbony ossicles that aid in the that aid in the amplification and transmission ofamplification and transmission of sound to the inner ear, and is sound to the inner ear, and is ventilated by theventilated by the eustachian tube, eustachian tube, which is connected to thewhich is connected to the nasopharynx.nasopharynx.

■ ■ The eustachian tube, which is lined with a mucousThe eustachian tube, which is lined with a mucous membrane that is membrane that is continuous with the nasopharynx,continuous with the nasopharynx, provides a passageway for provides 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, usually ear, 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 the loss occur when the tympanic membrane has beentympanic membrane has been perforated; air in the middle ear has perforated; 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 has ossicles has been impaired (otosclerosis).been impaired (otosclerosis).

HEARING LOSSHEARING LOSS■ Hearing loss represents

impairment of the ability to detect and perceive sound.

■ 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 inner ear.

■ 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 are The basal ganglia are

made up of:made up of: – – the the corpus striatumcorpus striatum

(consisting of the (consisting of the caudate caudate nucleus nucleus and the and the putamenputamen););

– – the inner and outer the inner and outer globus pallidusglobus pallidus (pallidum, consisting of an (pallidum, consisting of an internal and an external internal and an external part);part);

– – the the subthalamic subthalamic nucleusnucleus; and; and

– – the the substantia nigrasubstantia nigra (pars reticulata [p. r.] and (pars reticulata [p. r.] and pars compacta [p. c.]).pars compacta [p. c.]).

Their Their functionfunction is mainly is mainly to control movement in to control movement in conjunction with the conjunction with the cerebellum,motor cortex, cerebellum,motor cortex, corticospinal tracts, and corticospinal tracts, and motor nuclei in the brain motor nuclei in the brain stem. stem.

Parkinson’s Disease Parkinson’s disease is a disease Parkinson’s disease is a disease of the substantia nigra (p. c.) of the substantia nigra (p. c.) which via dopaminergic tracts which via dopaminergic tracts influences GABAergic cells in the influences GABAergic cells in the corpus striatum. The corpus striatum. The cause cause is is frequently a frequently a hereditary disposition hereditary disposition that in middle to old age leads to that in middle to old age leads to degeneration of dopaminergic degeneration of dopaminergic neurons in the substantia nigra. neurons in the substantia nigra. Further causes are Further causes are trauma trauma (e.g., (e.g., in boxers), in boxers), inflammation inflammation (encephalitis), (encephalitis), impaired circulation impaired circulation (atherosclerosis), (atherosclerosis), tumors tumors and and poisoning poisoning (especially by CO, (especially by CO, manganese, and 1-methyl-4-manganese, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine phenyl-1,2,3,6-tetrahydropyridine [MPTP], which was once used as [MPTP], which was once used as a substitute for heroin). The cell a substitute for heroin). The cell destruction probably occurs partly destruction probably occurs partly by apoptosis; superoxides are by apoptosis; superoxides are thought to play a causal role. For thought to play a causal role. For symptoms to occur, over 70% of symptoms 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 substantia The loss of cells in the substantia nigra (p. c.) decreases the nigra (p. c.) decreases the corresponding corresponding dopaminergic dopaminergic innervation innervation of the striatum.of the striatum.

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