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 -> (motor movement, sleep, dreaming, muscle) Alzheimer’s disease (lack of) Botulism: blocked Ach, paralysis Dopamine -> Parkinson’s disease (lack of) can be treated; also treats schizophrenia ( overload) / delusions Serotonin (5HT) -> sensitivity to it linked to depression (due to undersupply of it) Endorphins -> reduce pain Neuromodulators -> 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 disease m 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'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'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's head movements. A doll's head movement is that which occurs when the eyes stare forward, always following the position of the head. Normally, when an individual'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 thePathophysiology of thenervous system: violation ofnervous system: violation ofsensory, motor and trophicsensory, motor and trophicfunction.function.
Actuality of the lectureActuality of the lecture The nervous system as a main regulatory system of an organism in this or thatThe nervous system as a main regulatory system of an organism in this or thatmeasure participates in pathogenesis of each diseases. The earliest andmeasure participates in pathogenesis of each diseases. The earliest andobligatory form of participation of the nervous system in pathology isobligatory form of participation of the nervous system in pathology isdefensive 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-adrenalsystem 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 systembecomes the object of a defeat itself. It is defensive and adaptive thebecomes the object of a defeat itself. It is defensive and adaptive theresponse of the damaged nervous system are reduced, and it becomes aresponse of the damaged nervous system are reduced, and it becomes asource of pathological, harmful to an organism reflexes. Itself graving andsource of pathological, harmful to an organism reflexes. Itself graving andcharacter of violations of nervous activity depend on localization ofcharacter of violations of nervous activity depend on localization ofpathological 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 pathologicalprocess, but at the same time has signal and adaptive significance. Theprocess, but at the same time has signal and adaptive significance. Thedisturbance of nervous activity is always reflected in the function of internaldisturbance of nervous activity is always reflected in the function of internalorgans.organs. The fundamental knowledges of the reasons and mechanisms of disordersThe fundamental knowledges of the reasons and mechanisms of disordersmotor, sensitive and trophic functions of the nervous system are necessary formotor, sensitive and trophic functions of the nervous system are necessary forunderstanding of pathogenesis nervous diseases, and also many symptomsunderstanding of pathogenesis nervous diseases, and also many symptomsof a damage of internal organs.of a damage of internal organs.
CONTENTCONTENT• 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• DysphasiaDysphasia• Diseases of the Basal GangliaDiseases of the Basal Ganglia
A). Non nervousA). 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 sheathsform myelin sheathsTypes of cellsTypes of cells
Types ofTypes ofcellscellsB). NeuronsB). Neurons1). Structure1). StructureII).). cell bodycell body oror somasoma -- endoplasmicendoplasmicreticulum called thereticulum called the nissl bodynissl body..IIII).). ProcessesProcesses oror tracts (nerves)tracts (nerves)a).a). Dendrites:Dendrites: input regioninput regionb).b). Axon:Axon: Carries information awayCarries information awayc).c). Synaptic knobsSynaptic knobs oror AxonalAxonalterminalsterminals.. ReleasesReleasesneurotransmitters.neurotransmitters.2).2). AxonsAxonsa).a). myelin sheathmyelin sheath -- protects andprotects andelectrically insulates fibers conductelectrically insulates fibers conductnerve impulses faster thannerve impulses faster thannonmylenated fibers.nonmylenated fibers.b).b). nodes of Ranviernodes of Ranvier::spaces between the sheathsspaces between the sheathsThe action potential skips to the nodesThe action potential skips to the nodes
Nerve ImpulseNerve ImpulseA). TermsA). Terms1).1). Resting membrane PotentialResting membrane Potential:: PolarizedPolarized2).2). DepolarizationDepolarization:: Change in ion concentrationChange in ion concentration3).3). HyperpolarizationHyperpolarization Change in ion concentration insideChange in ion concentration insidebecomes more negativebecomes more negative4).4). Graded PotentialGraded Potential Localized change in ion; subthresholdLocalized change in ion; subthreshold5).5). Action PotentialAction Potential Change in ion concentration thatChange in ion concentration thatdoes not decrease over distance.does not decrease over distance.B).B). Action PotentialAction PotentialStages of an Action PotentialStages of an Action Potentialpolarized resting potentialpolarized resting potentialdepolarizesdepolarizesrepolarizesrepolarizesundershoot phaseundershoot phaseUndershooUndershoott :: the K+ channels stay openthe K+ channels stay openonce resting potential is reached;once resting potential is reached;hyperpolarizing the cell.hyperpolarizing the cell.
NerveNerve ImpulseImpulseC).C). PropagationPropagation Cannot be depolarized again until the membrane hasCannot be depolarized again until the membrane hasreached resting potential. The action potential moves at areached resting potential. The action potential moves at aconstant velocityconstant velocityD).D). All or none phenomenonAll or none phenomenon Not all depolarizations result in action potentials TheNot all depolarizations result in action potentials Thedepolarization must reach thedepolarization must reach the threshold pointthreshold pointE).E). Refractory periodRefractory period absolute refractory periodabsolute refractory period cannot respond to anothercannot respond to anotherstimuli.stimuli. relative refractory periodrelative refractory period -- The threshold is higherThe threshold is higherF). Impulse VelocityF). Impulse Velocity Strong stimuli result in more nerve impulses NotStrong stimuli result in more nerve impulses Notstronger impulses or fasterstronger impulses or faster
SynapseSynapse –– junction that carriesjunction that carriesinformation between neuronsinformation between neurons A). TypesA). Types1). Electrical synapse: ions to cross junction1). Electrical synapse: ions to cross junction2). Chemical synapse2). Chemical synapse neurotransmittersneurotransmittersB). Termination of neurotransmitterB). Termination of neurotransmitter 1). Degradation enzymes1). Degradation enzymes 2). Neurotransmitter reabsorbed2). Neurotransmitter reabsorbed 3). Diffusion of the neurotransmitter3). Diffusion of the neurotransmitterImpulseImpulsereleasesreleases 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 thedepolarization of postsynapticmembrane. Creating localized gradedresponse. (dendrites do not have actionpotentials) IF THE GRADED RESPONSE ISSTRONG ENOUGH TO BE CARRIEDTO THE AXON A FULL ACTIONPOTENTIAL WILL RESULTB). Inhibitory Synapses Binding neurotransmitters reducesthe postsynaptic membranes abilityto create an action potential.Induces hyperpolarization.Types of Neurotransmitters
C. Integration or Summation of Synaptic Events It takes more than one synaptic event to createan action potential. Presynaptic inhibition = excitatoryneurotransmitter by one neuron + inhibitoryneurotransmitter of another neuron
Division of the NervousSystemA). Central NervousSystem: (CNS)• Brain and Spinal CordonlyB). Peripheral NervousSystem• Outside CNS1). Sensory or afferentdivision:• Carries impulses to CNS2). Motor or efferentdivision• Carries impulses from theCNS.I). Somatic Nervous System• voluntaryII). Autonomic NervousSystem• involuntary• a. Parasympathetic• b. Sympathetic
The SympatheticThe SympatheticNervous SystemNervous System TheThe first fibersfirst fibers of the sympathetic nerves, called theof the sympathetic nerves, called thepreganglionic fiberspreganglionic fibers, leave from the thoracic or lumbar, leave from the thoracic or lumbarregions of the spine.regions of the spine. Soon afterSoon after leaving the spineleaving the spine, a preganglionic fiber, a preganglionic fiber joinsjoinsother 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 thesecond nerve fiber of the systemsecond nerve fiber of the system, the, the postganglionic fiberpostganglionic fiber,,andand releases acetylcholinereleases acetylcholine, which causes the, which causes thepostganglionic fiber to fire anpostganglionic fiber to fire an action potentialaction potential.. From theFrom the autonomic gangliaautonomic ganglia, the postganglionic fiber travels, the postganglionic fiber travelsto itsto its target organtarget organ, the muscle or gland., the muscle or gland. TheThe sympathetic postganglionic fibersympathetic postganglionic fiber usually releases theusually releases theneurotransmitter norepinephrineneurotransmitter norepinephrine.. Target organ receptors forTarget organ receptors fornorepinephrinenorepinephrine 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 cordfrom the sacral areafrom the sacral area.. TheThe preganglionic fiberpreganglionic fiber of theof the PNSPNS is typically long and travelsis typically long and travelsto an autonomic ganglionto an autonomic ganglion locatedlocated near the target organnear the target organ.. Preganglionic parasympathetic nervesPreganglionic parasympathetic nerves releaserelease acetylcholineacetylcholinethatthat then stimulates the postganglionic fiberthen stimulates the postganglionic fiber.. TheThe parasympathetic postganglionic fiberparasympathetic postganglionic fiber then travels a shortthen travels a shortdistancedistance to its target tissueto its target tissue, a, a muscle or a glandmuscle or a gland. This nerve. This nervealso releases acetylcholinealso releases acetylcholine.. Preganglionic acetylcholine receptorsPreganglionic acetylcholine receptors for sympathetic andfor sympathetic andparasympathetic fibersparasympathetic fibers are calledare called nicotinic receptorsnicotinic receptors.. Postganglionic acetylcholine receptorsPostganglionic acetylcholine receptors are calledare called muscarinicmuscarinicreceptorsreceptors. These names relate to the experimental. These names relate to the experimentalstimulation of the receptors bystimulation of the receptors by nicotinenicotine andand muscarinemuscarine (a(amushroom poison).mushroom poison).
Functions of the Sympathetic andFunctions of the Sympathetic andParasympathetic 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 arteriesandand veinsveins, causing, causing constriction of all vesselsconstriction of all vessels except theexcept thearterioles supplying skeletal musclearterioles supplying skeletal muscle.. Sympathetic nervesSympathetic nerves innervate theinnervate the smooth muscle of thesmooth muscle of thegutgut, causing, causing decreased motilitydecreased motility, and the, and the smooth muscle ofsmooth muscle ofthe respiratory tractthe respiratory tract, causing, causing bronchial relaxationbronchial relaxation andanddecreased bronchial secretionsdecreased bronchial secretions.. Sympathetic stimulationSympathetic stimulation affects theaffects the liverliver,, stimulatesstimulatessecretions of thesecretions of the sweat glandssweat glands, and is responsible for, and is responsible forejaculation during male orgasmejaculation during male orgasm.. Parasympathetic fibersParasympathetic fibers innervate theinnervate the heartheart,, slowing theslowing theheart rateheart rate, and the, and the gutgut, causing, causing increased motilityincreased motility.. Parasympathetic nervesParasympathetic nerves innervateinnervate bronchial smoothbronchial smoothmusclemuscle, causing, causing airway constrictionairway constriction, and the, and the genitourinarygenitourinarytracttract, causing, causing erection in the maleerection in the male..
The Autonomic Nervous SystemStructure Sympathetic Stimulation Parasympathetic StimulationIris (eye muscle) Pupil dilation Pupil constrictionSalivary Glands Saliva production reduced Saliva production increasedOral/Nasal Mucosa Mucus production reduced Mucus production increasedHeart Heart rate and force increased Heart rate and force decreasedLung Bronchial muscle relaxed Bronchial muscle contractedStomach Peristalsis reduced Gastric juice secreted; motilityincreasedSmall Intestine Motility reduced Digestion increasedLarge Intestine Motility reduced Secretions and motility increasedLiver Increased conversion of glycogento glucose---Kidney Decreased urine secretion Increased urine secretionAdrenal medulla Norepinephrine and epinephrinesecreted---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 theCNS 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 ison regions of the body wall isrequired torequired to initiate the sensory response.initiate the sensory response.■■ The system is organized intoThe system is organized into dermatomesdermatomes, with each, with eachsegment supplied by asegment supplied by a single dorsal root ganglionsingle dorsal root ganglion thatthatsequentially relays the sensory information tosequentially relays the sensory information to thethespinal cord, the thalamus, and the sensoryspinal cord, the thalamus, and the sensory cortexcortex..■■ Two pathwaysTwo pathways carry sensory information throughcarry sensory information through thetheCNSCNS. The. The discriminative pathwaydiscriminative pathway crosses in thecrosses in themedulla and relays touch and body position. Themedulla and relays touch and body position. Theanterolateral pathwayanterolateral pathway crosses in the spinal cordcrosses in the spinal cord andandrelays temperature and pain sensation fromrelays temperature and pain sensation from thetheopposite side of the body.opposite side of the body.
The Sensory Unit The somatosensory experience arises frominformation provided by a variety of receptorsdistributed throughout the body. There are four major modalities of sensoryexperience: (1) discriminative touch, which is required toidentify the size and shape of objects and theirmovement across the skin; (2) temperature sensation; (3) sense of movement of the limbs and jointsof 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 andandwhich arise owing to action on an organismwhich arise owing to action on an organismpainfulpainful ((nociceptivenociceptive)) irritantirritant oror weakeningweakeningofof antipainfulantipainful ((antinociceptiveantinociceptive)) systemsystem PainPain is an “unpleasant sensory andis an “unpleasant sensory andemotional experience associatedemotional experience associated withwithpotential tissue damage, or described inpotential tissue damage, or described interms ofterms of such damage.”such damage.”
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 itsorigin in the skin or subcutaneous tissues. Deep pain is a more diffuse and throbbing pain thatoriginates in structures such as the muscles, bones,and tendons and radiates to the surroundingtissues. Visceral pain is a diffuse and poorly defined painthat results from stretching, distention, or ischemiaof tissues in a body organ. Referred pain is pain that originates at a visceral sitebut is perceived as originating in part of the bodywall that is innervated by neurons entering the samesegment of the nervous system. Acute pain usually results from tissue damage andis characterized by autonomic nervous systemresponses. Chronic pain is persistent pain that is accompaniedby loss of appetite, sleep disturbances, depression,
PAIN SENSATION■ Pain is both a protective and an unpleasant physical and emotionallydisturbing sensation originating in pain receptors that respond to anumber of stimuli that threaten tissue integrity.■ There are two pathways for pain transmission:• The fast pathway for sharply discriminated pain that moves directlyfrom the receptor to the spinal cord using myelinated Aδ fibers and fromthe spinal cord to the thalamus using the neospinothalamic tract• The slow pathway for continuously conducted pain that is transmittedto the spinal cord using unmyelinated C fibers and from the spinal cordto the thalamus using the more circuitous and slower-conductingpaleospinothalamic tract.■ The central processing of pain information includes transmission to thesomatosensory cortex, where pain information is perceived andinterpreted; the limbic system, where the emotional components of painare experienced; and to brain stem centers, where autonomic nervoussystem responses are recruited.■ Modulation of the pain experience occurs by way of the endogenousanalgesic center in the midbrain, the pontine noradrenergic neurons,and the nucleus raphe magnus in the medulla, which sends inhibitorysignals to dorsal horn neurons in the spinal cord.
Classical and non-Classical and non-classical views of painclassical views of paintransmission and paintransmission and painmodulationmodulation (a).(a).Classical painClassical paintransmissiontransmissionpathwaypathway..(b):(b): Normal painNormal pain..Under basalUnder basalconditions, pain is notconditions, pain is notmodulated by glia.modulated by glia.(c)(c) Pain facilitation:Pain facilitation:classical view. Inclassical view. Inresponse to intenseresponse to intenseand/or prolongedand/or prolongedbarrages of incomingbarrages of incoming“pain” signals, the“pain” signals, thePTNs becomePTNs becomesensitized and over-sensitized and over-respond to subsequentrespond to subsequentincoming signalsincoming signals(d)(d) Pain facilitation:Pain facilitation:new view. Here, glialnew view. Here, glialactivation isactivation isconceptualized as aconceptualized as adriving force fordriving force forcreating andcreating andmaintaining painmaintaining painfacilitation.facilitation.
Pain TheoriesPain Theories Traditionally, two theories have been offered to explainTraditionally, two theories have been offered to explainthethe 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 separatesensory modality evoked bysensory modality evoked by the activity of specificthe activity of specificreceptors that transmit information toreceptors that transmit information to pain centers orpain centers orregions 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 theoriescollectivelycollectively referred to asreferred to as pattern theorypattern theory. It proposes that. It proposes thatpain receptorspain receptors share endings or pathways with othershare endings or pathways with othersensory modalitiessensory modalities but that different patterns of activity(i.e., spatial or temporal) of the same neurons can beused to signal painful and nonpainful stimuli. For example, light touch applied to the skin wouldproduce the sensation of touch through low-frequencyfiring of the receptor; intense pressure would producepain through high-frequency firing of the same receptor.
Gate control theoryGate control theory AA modification of specificity theory, wasmodification of specificity theory, was proposedproposedby Melzack and Wall in 1965 to meet theby Melzack and Wall in 1965 to meet thechallengeschallenges presented by the pattern theories. Thispresented by the pattern theories. Thistheory postulated thetheory postulated the presence of neural gatingpresence of neural gatingmechanisms at themechanisms at the segmental spinalsegmental spinal cord level tocord level toaccount for interactions between pain andaccount for interactions between pain andothersensory modalitiesothersensory modalities.. According to theAccording to the gate control theorygate control theory, the, theinternuncialinternuncial neuronsneurons involved in the gatinginvolved in the gatingmechanismmechanism are activatedare activated by large-diameter, faster-by large-diameter, faster-propagating fibers that carry tactilepropagating fibers that carry tactile informationinformation. The. Thesimultaneous firing of the large-diametersimultaneous firing of the large-diameter touchtouchfibersfibers has thehas the potential for blocking thepotential for blocking thetransmission oftransmission of impulsesimpulses from thefrom the small-diametersmall-diametermyelinated and unmyelinatedmyelinated and unmyelinated pain fiberspain fibers..
NNeuromatrixeuromatrix TTheoryheory More recently, Melzack has developed the neuromatrix theory toaddress further the brain’s role in pain as well as the multipledimensions and determinants of pain. This theory is particularly usefulin understanding chronic pain and phantom limb pain, in whichthere is not a simple one-to-one relationship between tissue injury andpain experience. The neuromatrix theory proposes that the brain contains a widelydistributed neural network, called the body-self neuromatrix, thatcontains somatosensory, limbic, and thalamocortical componentssomatosensory, limbic, and thalamocortical components. Genetic and sensory influences determine the synapticarchitecture of an individual’s neuromatrix that integrates multiplesources of input and evokes the sensory, affective, and cognitivedimensions 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 deficitin pain and temperature discrimination andmay also produce abnormal painfulsensations (dysesthesias) usually in thearea of sensory loss. Such pain is termedneuropathic pain and often has a strangeburning, tingling, or electric shocklike quality.It may arise from several mechanisms.• Damaged peripheral nerve fibers becomehighly mechanosensitive and may firespontaneously without known stimulation.They also develop sensitivity tonorepinephrine released from sympatheticpostganglionic neurons.• Electrical impulses may spread abnormallyfrom one fiber to another (ephapticconduction), enhancing the spontaneousfiring of multiple fibers.• Neuropeptides released by injured nervesmay recruit an inflammatory reaction thatstimulates pain. In the dorsal horn,denervated spinal neurons may becomespontaneously active.• In the brain and spinal cord, synapticreorganization occurs in response to injuryand may lower the threshold for pain. Inaddition, inhibition of pathways that modulatetransmission of sensory information in thespinal cord and brainstem may promoteneuropathic pain.
PainPain Free nerve endingsFree nerve endings of unmyelinatedof unmyelinatedC fibers and small-diameter myelinatedC fibers and small-diameter myelinatedAAδδ fibers in the skin convey sensoryfibers in the skin convey sensoryinformation in response toinformation in response to chemical,chemical,thermal, and mechanical stimulithermal, and mechanical stimuli.. Intense stimulationIntense stimulation of these nerveof these nerveendingsendings evokes the sensation of painevokes the sensation of pain.. In contrast to skin, most deep tissuesIn contrast to skin, most deep tissuesare relatively insensitive to chemical orare relatively insensitive to chemical ornoxious stimuli.noxious stimuli. However, inflammatory conditions canHowever, inflammatory conditions cansensitize sensory afferents from deepsensitize sensory afferents from deeptissues to evoke pain on mechanicaltissues to evoke pain on mechanicalstimulation. This sensitization appearsstimulation. This sensitization appearsto beto be mediated bymediated by bradykinin,bradykinin,prostaglandins, and leukotrienesprostaglandins, and leukotrienesreleased during the inflammatoryreleased during the inflammatoryresponse.response. Information fromInformation from primary afferent fibersprimary afferent fibersis relayedis relayed via sensory gangliavia sensory ganglia to theto thedorsal horn of the spinal corddorsal horn of the spinal cord and thenand thento theto the contralateral spinothalamic tractcontralateral spinothalamic tract,,which connects towhich connects to thalamic neuronsthalamic neuronsthat project to thethat project to the somatosensorysomatosensorycortexcortex..
Primary pain pathwaysNociceptiveNociceptivestimulistimuliSomesthetic association cortexSomesthetic association cortex(perception and meaning)(perception and meaning)Limbic cortexLimbic cortex(emotional experience)(emotional experience)PontinePontinenoradrenergic neuronsnoradrenergic neuronsPrimary somesthetic cortexPrimary somesthetic cortex(discrimination: location and intensity)(discrimination: location and intensity)Medullary raphe nucleusMedullary raphe nucleusThalamus (sensation)Thalamus (sensation)Somesthetic nucleiSomesthetic nucleiSpinal cord and dorsal hornSpinal cord and dorsal hornpain modulating circuitspain modulating circuitsPeriaqueductal gray (PAG)Periaqueductal gray (PAG)(endogenous analgesic center)(endogenous analgesic center)Medullary NRMMedullary NRMNeospinothalamictractNeospinothalamictract(sharp,brightpain)(sharp,brightpain)PaleospinothalamictractPaleospinothalamictract(dull,achingpain)(dull,achingpain)Primary touch fibersA-delta(fast)C-fiber(slow)
Characteristics ofCharacteristics ofAcute and Chronic PainAcute and Chronic PainCharacteristic Acute Pain Chronic PainOnsetRecent Continuous orintermittentDuration Short duration (<6 months) 6 months or moreAutonomic responsesConsistent with sympatheticfight-orflight response*Increased heart rateIncreased stroke volumeIncreased blood pressureIncreased pupillary dilationIncreased muscle tensionDecreased gut motilityDecreased salivary flow (drymouth)Absence of autonomicresponsesPsychological componentAssociated anxiety Increased irritabilityAssociated depressionSomatic preoccupationWithdrawal from outsideinterestsDecreased strength ofrelationshipsOther types of responseDecreased sleepDecreased libidoAppetite changes
Pain Threshold and ToleranceCando Baseline Dolorimeter Pain threshold and tolerance affect anindividual’s response to a painful stimulus.Although the terms often are usedinterchangeably, pain threshold and paintolerance have distinct meanings. Painthreshold is closely associated with tissuedamage and the point at which a stimulus isperceived as painful. Pain tolerance relates more to the total painexperience; it is defined as the maximumintensity or duration of pain that a person iswilling to endure before the person wantssomething done about the pain.Psychological, familial, cultural, andenvironmental factors significantly influencethe amount of pain a person is willing totolerate. The threshold to pain is fairly uniformfrom one person to another, whereas paintolerance is extremely variable. Separationand identification of the role of each of thesetwo aspects of pain continue to posefundamental problems for the painmanagement 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 beexplosive and radiates through a peripheral nerve distribution. It isassociated with pathologic changes in peripheral nerves, such aslocalized ischemia. Spontaneous, unpleasant sensations called paresthesias occur withmore severe irritation (e.g., the pins-and-needles sensation thatfollows temporary compression of a peripheral nerve). The general term dysesthesia is given to distortions (usuallyunpleasant) of somesthetic sensation that typically accompany partialloss of sensory innervation.
Alterations in Pain SensitivityAlterations in Pain Sensitivity• Severe pathologic processes can result in reduced or losttactile (e.g., hypoesthesia, anesthesia), temperature (e.g.,hypothermia, athermia), and pain sensation (i.e.,hypalgesia).• Analgesia is the absence of pain on noxious stimulation orthe relief of pain without loss of consciousness. The inability tosense pain may result in trauma, infection, and even loss of abody part or parts. Inherited insensitivity to pain may take theform of congenital indifference or congenital insensitivity topain.• Allodynia (Greek allo, “other,” and odynia, “painful”) is theterm used for the puzzling phenomenon of pain that follows anon-noxious stimulus to apparently normal skin. This term isintended to refer to instances in which otherwise normaltissues may be abnormally innervated or may be referral sitesfor other loci that give rise to pain with non-noxious stimuli.• Trigger points are highly localized points on the skin ormucous membrane that can produce immediate intense painat that site or elsewhere when stimulated by light tactilestimulation.
NeuralgiaNeuralgia NeuralgiaNeuralgia is characterized by severe, brief,is characterized by severe, brief,often repetitive attacksoften repetitive attacks of lightning-like orof lightning-like orthrobbing pain. It occurs along the distributionthrobbing pain. It occurs along the distribution ofofa spinal or cranial nerve and usually isa spinal or cranial nerve and usually isprecipitatedprecipitated by stimulation of the cutaneousby stimulation of the cutaneousregion supplied by that nerve.region supplied by that nerve. Trigeminal Neuralgia.Trigeminal Neuralgia.Trigeminal neuralgia, orTrigeminal neuralgia, or ticticdouloureuxdouloureux,, is one of theis one of themost common and severemost common and severeneuralgias. It is manifestedneuralgias. It is manifestedbyby facial ticsfacial tics oror grimacesgrimacesand characterized byand characterized bystabbing,stabbing, paroxysmalparoxysmalattacks of pain that usuallyattacks of pain that usuallyare limited to the unilateralare limited to the unilateralsensory distribution of onesensory distribution of oneor more branches of theor more branches of thetrigeminal nerve, mosttrigeminal nerve, mostoften the maxillary oroften the maxillary ormandibular divisions.mandibular divisions.
Postherpetic Neuralgia.Postherpetic Neuralgia.Postherpetic pain is painPostherpetic pain is painthat persiststhat persists as aas acomplication of herpescomplication of herpeszoster or shingles. Itzoster or shingles. Itdescribes thedescribes the presence ofpresence ofpain more than 1 monthpain more than 1 monthafter the onset of theafter the onset of theacuteacute attack.attack.Postherpetic neuralgiaPostherpetic neuralgiadevelops in from 10% todevelops in from 10% to70% of70% of patients withpatients withshingles; the riskshingles; the riskincreases with age.increases with age.The pain ofThe pain of postherpeticpostherpeticneuralgia occurs in theneuralgia occurs in theareas of innervation ofareas of innervation ofthethe infected gangliainfected ganglia..During the acute attack ofDuring the acute attack ofherpes zosterherpes zoster, the, thereactivated virus travelsreactivated virus travelsfrom the ganglia to thefrom the ganglia to theskin of the correspondingskin of the correspondingdermatomes, causingdermatomes, causinglocalized vesicularlocalized vesiculareruptioneruption and hyperpathiaand hyperpathia((i.e.i.e., abnormally, abnormallyexaggerated subjectiveexaggerated subjectiveresponseresponse to pain).to pain).
Phantom Limb PainPhantom Limb Pain• Phantom limb pain, a type ofneurologic pain, followsamputation of a limb or part of alimb. As many as 70% of thosewho under amputationexperience phantom pain.• The pain often begins assensations of tingling, heat andtingling, heat andcold, or heaviness,cold, or heaviness, followed byfollowed byburning, cramping, or shootingburning, cramping, or shootingpainpain. It may disappearspontaneously or persist formany years. One of the moretroublesome aspects of phantompain is that the person mayexperience painful sensationsthat were present before theamputation, such as that of apainful 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 scartissue of the amputation site. It is known that when a peripheral nerve is cut, the scartissue that forms becomes a barrier to regenerating outgrowth of the axon. Thegrowing axon often becomes trapped in the scar tissue, forming a tangled growth(i.e., neuroma) of smalldiameter axons, including primary nociceptive afferents andsympathetic efferents. It has been proposed that these afferents show increasedsensitivity to innocuous mechanical stimuli and to sympathetic activity and circulatingcatecholamines.• 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 neuronsthat have lost their normal sensory input from the body. In this case, a closedself-exciting neuronal loop in the posterior horn of the spinal cord is postulated tosend impulses to the brain, resulting in pain. Even the slightest irritation to theamputated limb area can initiate this cycle.• Other theories propose that the phantom limb pain may arise in the brain. In onehypothesis, the pain is caused by changes in the flow of signals throughsomatosensory areas of the brain.• Treatment ofphantom limb painhas beenaccomplished by theuse of sympatheticblocks, TENS of thelarge myelinatedafferents innervatingthe area, hypnosis,and relaxationtraining.
Antinociceptive systemsAntinociceptive systems NeuronalNeuronal opiate systemopiate system –– metmet-- and leuencephalinand leuencephalin NeuronalNeuronal unopiate systemunopiate system –– noradrenalinnoradrenalin,, serotoninserotonin,,dopaminedopamine HormonalHormonal opiate systemopiate system –– hormoneshormones ofofadenohypophysisadenohypophysis HormonalHormonal unopiate systemunopiate system –– vasopressinvasopressin
1.1. Opening of abscessOpening of abscess2.2. Reposition ofReposition offragmentsfragments3.3. Splintation of extremitySplintation of extremity4.4. Section of scarsSection of scars5.5. DesympathizationDesympathization1.1. AcupunctureAcupuncture2.2. ElectroacupunctureElectroacupuncture3.3. LaseropunctureLaseropuncture4.4. ElectrostimulationElectrostimulation5.5. ElectrophoresisElectrophoresis6.6. UltrasoundUltrasound7.7. Magnetico-laserMagnetico-laser therapytherapy8.8. MassageMassage9.9. ManualManual therapytherapyMETHODS OFANAESTIZATION PsycologicalPsycological PhysicalPhysical PharmacologicalPharmacological SurgicalSurgical NeurosurgicalNeurosurgical1.1. ConversationConversation2.2. RelaxationRelaxation3.3. HypnosisHypnosis4.4. AutotrainingAutotraining5.5. CorrectCorrect stereotypestereotype of motionof motion6.6. 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 bydischarges from prefrontal, somatosensory, visual,or auditory cortices, which are then followed bymotor cortex pyramidal cell discharges that occurseveral milliseconds before the onset of movement AnatomyAnatomy TheThe motor cortexmotor cortex is theis theregion from whichregion from whichmovements can be elicitedmovements can be elicitedby electrical stimuli (Figure).by electrical stimuli (Figure). This includes: the primary motor area(Brodmann area 4), premotor cortex (area 6), supplementary motorcortex (medial portions of 6), primary sensory cortex(areas 3, 1, and 2). In the motor cortex, groupsof neurons are organized invertical columns, anddiscrete groups controlcontraction of individualmuscles.
► Cortical motor neuronsCortical motor neurons contribute axons thatcontribute axons thatconverge in the corona radiata and descend in theconverge in the corona radiata and descend in theposterior limb of the internal capsule, cerebralposterior limb of the internal capsule, cerebralpeduncles, ventral pons, and medullapeduncles, ventral pons, and medulla. These fibers. These fibersconstitute theconstitute the corticospinalcorticospinal andand corticobulbarcorticobulbartractstracts and together areand together are known as upper motorknown as upper motorneuron fibersneuron fibers. As they descend through the. As they descend through thediencephalon and brainstem, fibers separate todiencephalon and brainstem, fibers separate toinnervate extrapyramidal and cranial nerve motorinnervate extrapyramidal and cranial nerve motornuclei. The lower brainstem motor neurons receivenuclei. The lower brainstem motor neurons receiveinput from crossed and uncrossed corticobulbarinput from crossed and uncrossed corticobulbarfibers, although neurons that innervate lower facialfibers, although neurons that innervate lower facialmuscles receive primarily crossed fibers.muscles receive primarily crossed fibers.► In the ventral medulla, the remaining corticospinalIn the ventral medulla, the remaining corticospinalfibers course in a tract that is pyramidal in shape infibers course in a tract that is pyramidal in shape incross section—thus, the namecross section—thus, the name pyramidal tract.pyramidal tract. AtAtthethe lower end of the medullalower end of the medulla, most fibers decussate,, most fibers decussate,although the proportion of crossed and uncrossedalthough the proportion of crossed and uncrossedfibers varies somewhat between individuals. Thefibers varies somewhat between individuals. Thebulk of these fibers descend as the lateralbulk of these fibers descend as the lateralcorticospinal tract of the spinal cord.corticospinal tract of the spinal cord.► Different groups of neurons in the cortex controlDifferent groups of neurons in the cortex controlmuscle groups of the contralateral face, arm, andmuscle groups of the contralateral face, arm, andleg. Neurons near the ventral end of the centralleg. Neurons near the ventral end of the centralsulcus control muscles of the face, whereassulcus control muscles of the face, whereasneurons on the medial surface of the hemisphereneurons on the medial surface of the hemispherecontrol leg muscles. Because thecontrol leg muscles. Because the movements of themovements of theface, tongue, and hand are complex in humans, aface, tongue, and hand are complex in humans, alarge share of the motor cortex is devoted to theirlarge share of the motor cortex is devoted to theircontrolcontrol. A somatotopic organization is also apparent. A somatotopic organization is also apparentin the lateral corticospinal tract of the cervical cord,in the lateral corticospinal tract of the cervical cord,where fibers to motor neurons that control legwhere fibers to motor neurons that control legmuscles lie laterally and fibers to cervical motormuscles lie laterally and fibers to cervical motorneurons lie medially.neurons lie medially.
Upper and Lower motoneurons innervate the skeletalUpper and Lower motoneurons innervate the skeletalmusclesmuscles aand are essential for motor function.nd are essential for motor function.Amyotrophic lateral sclerosis (ALS)Amyotrophic lateral sclerosis (ALS), fatal combined degeneration ofmotoneurons and motor fiber tracts (i.e. combined gray and white matter disease).Motoneurons of entire neuraxis! ALS - most devastating neurodegenerativedisease of aging CNS that so resembles Alzheimer and Parkinson diseases.
Upper and Lower motoneurons innervate the skeletalUpper and Lower motoneurons innervate the skeletalmusclesmuscles aand are essential for motor function.nd are essential for motor function.• Amyotrophic lateral sclerosis (ALS), also known as LouGehrig’s disease after the famous New York Yankeesbaseball player, is a devastating neurologic disorder thatselectively affects motor function. ALS is primarily a disorderof middle to late adulthood, affecting persons between 55and 60 years of age, with men developing the disease nearlytwice 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) → lossof large myelinated fibers in anterior & lateral spinalcolumns (gliotic sclerosis of lateral columns = LATERALSCLEROSIS)N.B. posterior columns are usually spared in SALS.• 2. Brain stem - lower nuclei are more often / moreextensively involved than upper nuclei (e.g. oculomotornuclei loss is modest and rarely demonstrable clinically,whereas hypoglossal nuclei are prominently degenerated).• 3. Spinal anterior horns → loss of myelinated fibers inanterior root →muscle denervation atrophy(AMYOTROPHY); reinnervation is possible (but much lessextensive as in poliomyelitis, peripheral neuropathy).
Amyotrophic lateral sclerosisAmyotrophic lateral sclerosisCytoplasmic ultrastructural abnormalities (cytoskeleton is affectedCytoplasmic ultrastructural abnormalities (cytoskeleton is affectedearly!):early!):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 cytoplasmicstructures, such as mitochondria).structures, such as mitochondria).some patients have mutations insome patients have mutations in neurofilament heavy chain subunitneurofilament heavy chain subunit(22q).(22q).abnormal neurofilaments interfere with axonal transport, resulting inabnormal neurofilaments interfere with axonal transport, resulting infailure to maintain axonal structure and transport of macromoleculesfailure to maintain axonal structure and transport of macromoleculessuch 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 toneurofilaments, ubiquitinneurofilaments, ubiquitin ((marker for degenerationmarker for degeneration)), and gene encoding, and gene encodingCu/Zn superoxide dismutase [SOD1]).Cu/Zn superoxide dismutase [SOD1]).Number of abnormalities inNumber of abnormalities in GLUTAMATEGLUTAMATE metabolism have beenmetabolism have beenidentified in ALS (incl. alterations in tissue glutamate levels, transporteridentified in ALS (incl. alterations in tissue glutamate levels, transporterproteins, 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 TRANSPORTactivity*activity* in motor cortex and spinal cord (but not in other regions ofin motor cortex and spinal cord (but not in other regions ofcentral 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 inmRNA splicing).mRNA splicing).
DemyelinationDemyelination In myelinated nerves, the axon between two nodes of Ranvier (internodalIn myelinated nerves, the axon between two nodes of Ranvier (internodalsegment) is surrounded by asegment) is surrounded by a myelin sheathmyelin sheath. This is a precondition for. This is a precondition forsaltatory conduction of the action potentials, i.e., the “jumping” propagationsaltatory conduction of the action potentials, i.e., the “jumping” propagationof excitation from one nodal constriction (R1) to the next (R2). Theof excitation from one nodal constriction (R1) to the next (R2). Theinternodal 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 thecurrent from the first node (R1). However, the current is usually so strongcurrent from the first node (R1). However, the current is usually so strongthat 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 thecurrent will diminish. First of all, the membrane in the internodal segmentcurrent will diminish. First of all, the membrane in the internodal segmentmust change its polarity, i.e., themust change its polarity, i.e., the membrane capacitancemembrane capacitance must bemust bedischarged, for which a current is needed. Secondly, current can alsodischarged, for which a current is needed. Secondly, current can alsoescape through individualescape through individual ionic channelsionic channels in the axonal membrane (orangein the axonal membrane (orangearrow). However, myelination of the internodal segment causes thearrow). However, myelination of the internodal segment causes themembrane resistance (Rm) to be elevated and the capacity (Cm) of themembrane resistance (Rm) to be elevated and the capacity (Cm) of themembrane 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 veryhigh because of the low density of ionic channels there. Furthermore, thehigh because of the low density of ionic channels there. Furthermore, theperimembranous space is insulated by a layer of fat from the freeperimembranous space is insulated by a layer of fat from the freeextracellular space. The lowextracellular space. The low capacitancecapacitance of the condensor is due to theof the condensor is due to thelarge distance between the interior of the axon and the free extracellularlarge distance between the interior of the axon and the free extracellularspace 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 betweenthem.them.
DemyelinationDemyelination can becan becaused by degenerative,caused by degenerative,toxic, or inflammatorytoxic, or inflammatorydamage to the nerves,damage to the nerves,or by a deficiency ofor by a deficiency ofvitamins B6 or B12.vitamins B6 or B12.If this happens, Rm willIf this happens, Rm willbe reduced and Cmbe reduced and Cmraised in the internodalraised in the internodalsegment.segment.As a result, more currentAs a result, more currentwill be required towill be required tochange the polarity ofchange the polarity ofthe internodal segmentthe internodal segmentand, through opening upand, through opening upthe ionic channels, largethe ionic channels, largelosses of current maylosses of current mayoccur.occur.
Multiple SclerosisMultiple Sclerosis• Multiple sclerosisMultiple sclerosis (MS), a demyelinating disease of the CNS, is a major cause ofneurologic disability among young and middleaged adults. Approximately two thirdsof 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 exacerbationsand remissions over many years in several different sites in the CNS.• Initially, there is normal or nearnormal neurologic function between exacerbations. Asthe disease progresses, there is less improvement between exacerbations andincreasing neurologic dysfunction.
Huntingtons diseaseHuntingtons disease Huntingtons diseaseHuntingtons disease is inherited as anis inherited as anautosomal 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, jerkymovements (movements (choreachorea) and slow writhing) and slow writhingmovements of the proximal limbs and trunkmovements 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 withpatients develop signs of parkinsonism withtremor (cogwheeling) and stiffness. Thetremor (cogwheeling) and stiffness. Thespiny GABAergic neuronsspiny GABAergic neurons of the striatumof the striatumpreferentially degenerate, resulting in a netpreferentially degenerate, resulting in a netdecrease in GABAergic output from thedecrease in GABAergic output from thestriatum. This contributes to thestriatum. This contributes to thedevelopment of chorea and athetosis.development of chorea and athetosis. DopamineDopamine antagonists, which blockantagonists, which blockinhibition of remaining striatal neurons byinhibition of remaining striatal neurons bydopaminergic striatal fibers, reduce thedopaminergic striatal fibers, reduce theinvoluntary movements. Neurons in deepinvoluntary movements. Neurons in deeplayers of the cerebral cortex alsolayers of the cerebral cortex alsodegenerate early in the disease, and laterdegenerate early in the disease, and laterthis extends to other brain regions, includingthis extends to other brain regions, includingthe hippocampus and hypothalamus. Thus,the hippocampus and hypothalamus. Thus,the disease is characterized by cognitivethe disease is characterized by cognitivedefects and psychiatric disturbances indefects and psychiatric disturbances inaddition to the movement disorder.addition to the movement disorder.
HUNTINGTON DISEASEHUNTINGTON DISEASEClassical familial,Classical familial,genetic diseasegenetic diseaseProgressiveProgressivemotor loss andmotor loss anddementiadementia““chorea”, i.e.chorea”, i.e.“jerky”“jerky”movementsmovementsProgressive, fatalProgressive, fatalAtrophy of basalAtrophy of basalganglia, i.e.,ganglia, i.e.,corpus striatumcorpus striatum Cortical (basal ganglia) atrophyCortical (basal ganglia) atrophyVentricular enlargementVentricular enlargement
Discriminative SensationDiscriminative Sensation Primary sensory cortex providesPrimary sensory cortex providesawareness of somatosensory informationawareness of somatosensory informationand the ability to make sensoryand the ability to make sensorydiscriminations.discriminations. Touch, pain, temperature, and vibrationTouch, pain, temperature, and vibrationsense are considered the primarysense are considered the primarymodalities of sensation and are relativelymodalities of sensation and are relativelypreserved in patients with damage topreserved in patients with damage tosensory cortex or its projections from thesensory cortex or its projections from thethalamus.thalamus. In contrast, complex tasks that requireIn contrast, complex tasks that requireintegration of multiple somatosensoryintegration of multiple somatosensorystimuli and of somatosensory stimuli withstimuli and of somatosensory stimuli withauditory or visual information are impaired.auditory or visual information are impaired. These include the ability to distinguishThese include the ability to distinguish twotwopointspoints from one when touched on the skinfrom one when touched on the skin((two-point discriminationtwo-point discrimination), localize tactile), localize tactilestimuli, perceive the position of body partsstimuli, perceive the position of body partsin space, recognize letters or numbersin space, recognize letters or numbersdrawn on the skin (drawn on the skin (graphesthesiagraphesthesia), and), andidentify objects by their shape, size, andidentify objects by their shape, size, andtexture (texture (stereognosisstereognosis).).
Anatomy of Sensory LossAnatomy of Sensory LossThe patterns of sensory loss often indicatethe level of nervous system involvement.Symmetric distal sensory loss in the limbs,affecting the legs more than the arms,usually signifies a generalized disorder ofmultiple peripheral nerves(polyneuropathy).Sensory symptoms and deficits may berestricted to the distribution of a singleperipheral nerve (mononeuropathy) ortwo or more peripheral nerves(mononeuropathy multiplex).Symptoms limited to a dermatome indicatea spinal root lesion (radiculopathy).
Alterations in Motor Responses andAlterations in Motor Responses andMovementMovement Abnormal motor responses include inappropriate or absentAbnormal motor responses include inappropriate or absentmovements in response to painful stimuli. Brainstemmovements in response to painful stimuli. Brainstemreflexes such as sucking and grasping responses will occurreflexes such as sucking and grasping responses will occurif higher brain centers have been damaged.if higher brain centers have been damaged. Flexion and rigidity of limbs also are motor responsesFlexion and rigidity of limbs also are motor responsesindicative of brain damage.indicative of brain damage. Muscle conditionsMuscle conditions that indicate abnormal brain functionthat indicate abnormal brain functionincludeinclude hyperkinesiahyperkinesia ((excessive muscle movementsexcessive muscle movements),),hypokinesiahypokinesia ((decreased muscle movementsdecreased muscle movements),), paresisparesis((muscle weaknessmuscle weakness), and), and 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 ofbrainstem function, results in a particular body posturebrainstem function, results in a particular body posturecalledcalled flexor posturingflexor posturing.. Flexor posturingFlexor posturing is characterized by flexion of the upperis characterized by flexion of the upperextremities at the elbows and external rotation andextremities at the elbows and external rotation andextension of the lower extremities. This postureextension of the lower extremities. This posture may bemay beunilateral or bilateralunilateral or bilateral. Extensor posturing occurs with severe. Extensor posturing occurs with severeinjury to higher brain centers and the brainstem and isinjury to higher brain centers and the brainstem and ischaracterized bycharacterized by rigid extension of the limbs and neckrigid extension of the limbs and neck..
Brown-Séquard syndromeIn the spinal cord, segregation of fiber tracts and thesomatotopic arrangement of fibers give rise to distinctpatterns of sensory loss. Loss of pain andtemperature sensation on one side of the bodyand of proprioception on the opposite side occurswith lesions that involve one half of the cord on theside of the proprioceptive deficit (Brown-Séquardsyndrome).Compression of the upper spinal cord causes loss ofpain, temperature, and touch sensation first inthe legs, because the leg spinothalamic fibers aremost superficial. More severe cord compressioncompromises fibers from the trunk. In patients withspinal cord compression, the lesion is often abovethe highest dermatome involved in the deficit. Thus,radiographic studies should be tailored to visualizethe cord at and above the level of the sensory deficitdetected on examination.Intrinsic cord lesions that involve the central portionsof the cord often impair pain and temperaturesensation at the level of the lesion because the fiberscrossing the anterior commissure and entering thespinothalamic tracts are most centrally situated.Thus, enlargement of the central cervical canal insyringomyelia typically causes loss of pain andtemperature sensation across the shoulders andupper arms.
InjuryLevelSegmental Sensorimotor Function Dressing, Eating Elimination MobilityC1 Little or no sensation or control of head andneck; no diaphragm control; requires continuousventilationDependent Dependent Limited. Voice or sip-n-puffcontrolled electric wheelchairC2 toC3Head and neck sensation; some neck control.Independent of mechanical ventilation for shortperiodsDependent Dependent Same as for C1C4 Good head and neck sensation and motorcontrol; some shoulder elevation; diaphragmmovementDependent; may beable to eat withadaptive slingDependent Limited to voice, mouth, head,chin, or shoulder-controlledelectric wheelchairC5 Full head and neck control; shoulder strength;elbow flexionIndependent withassistanceMaximal assistance Electric or modified manualwheel chair, needs transferassistanceC6 Fully innervated shoulder; wrist extension ordorsiflexionIndependent or withminimal assistanceIndependent or withminimal assistanceIndependent in transfers andwheelchairC7 toC8Full elbow extension; wrist plantar flexion; somefinger controlIndependent Independent Independent; manual wheelchairT1 toT5Full hand and finger control; use of intercostaland thoracic musclesIndependent Independent Independent; manual wheelchairT6 toT10Abdominal muscle control, partial to goodbalance with trunk musclesIndependent Independent Independent; manual wheelchairT11 toL5Hip flexors, hip abductors (L1–3); kneeextension (L2–4); knee flexion and ankledorsiflexion (L4–5)Independent Independent Short distance to full ambulationwith assistanceS1 toS5Full leg, foot, and ankle control; innervation ofperineal muscles for bowel, bladder, and sexualfunction (S2–4)Independent Normal to impairedbowel and bladderfunctionAmbulate independently with orwithout assistanceFunctional 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 LOSSBELOW THE LEVEL OF LESION• PRIAPISM• BULBOCAVERNOUS REFLEX IS LOST BUT REUTRNSAFTER A FEW HRS• OTHER REFLEXES REMAIN ABSENT• 3-6 WKSUTONOMIC DISTURBANCES:UTONOMIC DISTURBANCES:WEATING IS ABOLISHEDBELOW THE LEVEL OF INJURYRINE & FECES RETAINEDASTRIC ATONYRTHOSTATIC HYPOTENSIONLOW, & STEADY PULSE
REFLEX ACTIVITYREFLEX ACTIVITY• REPLACE SPINAL SHOCK AFTER 2-3WEEKS IF LUMBO-SACRAL SEGMENTSARE UNDAMAGED• OCCURS IN ACUTE SPINAL INJURY,NOT IN PROGRESSIVE ONES• AUTOMATIC BLADDER; REFLEXSWEATING & DEFECATION• FIRST SIGN OF WEARING OFF:– CONTRACTION OF HAMSTRING– FLEXION/ EXTENSION OF TOES WITHPLANTAR STIMULATION
ParalysisParalysis ParalysisParalysis is the loss of sensory and voluntary motoris the loss of sensory and voluntary motorfunction. With spinal cord transection, paralysis isfunction. With spinal cord transection, paralysis ispermanent.permanent. ParalysisParalysis of theof the upper and lower extremitiesupper and lower extremities occurs withoccurs withtransection of the cord at level C6 or higher and is calledtransection of the cord at level C6 or higher and is calledquadriplegiaquadriplegia.. ParalysisParalysis of the lower half of the body occurs withof the lower half of the body occurs withtransection of the cord below C6 and is calledtransection of the cord below C6 and is calledparaplegiaparaplegia.. If only one half of the cord is transectedIf only one half of the cord is transected,, hemiparalysishemiparalysismay occur.may occur. Permanent paralysisPermanent paralysis may occur even when the cord ismay occur even when the cord isnot transected, as a result of the destruction of thenot transected, as a result of the destruction of thenerves 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 canlead to clinically complete lesions, even though thelead to clinically complete lesions, even though thespinal 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 ofthe inflammatory response to cord injury.the inflammatory response to cord injury.
ClinicalManifestationsof Paralysis• Loss of sensation,motor control, andreflexes below thelevel of injury, andup to two levelsabove, will occur.Body temperaturewill reflect ambienttemperature, andblood pressure willbe reduced.• The pulse rate isoften normal, withlow blood pressure.
Complications• If damage and swelling around the cord is in thecervical spine (down to approximately C5),respirations may cease because of compression ofthe phrenic nerve, which exits between C3 and C5and controls the movement of the diaphragm.• Autonomic hyper-reflexia is characterized by highblood pressure with bradycardia (low heart rate),and sweating and flushing of the skin on the faceand upper torso.• In the past, individuals suffering from a C2 or highertransection invariably died as a result of respiratoryarrest. Although this is still true for many, recentadvances in treatment modalities and betteremergency rescue service responses have resultedin the survival of many individuals with high cordtransection.• A severe spinal cord injury affects virtually allsystems of the body to some degree. Commonly,urinary tract and kidney infections, skin breakdownand the development of pressure ulcers, and muscleatrophy occur. Depression, marital and familystress, loss of income, and large medical expensesare 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 oftenDysphasia usually results from cerebral hypoxia, which is oftenassociated with a stroke but can result from trauma or infection. Brainassociated with a stroke but can result from trauma or infection. Braindamage leading to dysphasia usually involves the left cerebraldamage leading to dysphasia usually involves the left cerebralhemisphere.hemisphere. Brocas dysphasia results from damage to Brocas area in the frontalresults from damage to Brocas area in the frontallobe. Persons with Brocas dysphasia will understand language, butlobe. Persons with Brocas dysphasia will understand language, buttheir ability to meaningfully express words in speech or writing will betheir ability to meaningfully express words in speech or writing will beimpaired. This is called expressive dysphasia.impaired. This is called expressive dysphasia. Wernickes dysphasia results from damage to Wernickes area in theresults from damage to Wernickes area in theleft temporal lobe. With Wernickes dysphasia, verbal expression ofleft temporal lobe. With Wernickes dysphasia, verbal expression oflanguage is intact, but meaningful understanding of spoken or writtenlanguage is intact, but meaningful understanding of spoken or writtenwords 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 inabilityto 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 fromdamage to a particular primary or associative sensory area in thedamage to a particular primary or associative sensory area in thecerebral cortex.cerebral cortex.
Alterations in Pupil Responses• The ability of our eyes to dilate orconstrict, rapidly and equally,depends on an intact brainstem.• Cerebral hypoxia and many drugschange pupil size and reactivity.Therefore, pupil size and reactivityoffer valuable information concerningbrain integrity and function.• Important pupil changes seen withbrain damage are pinpoint pupilsseen with opiate (heroin) overdoseand bilaterally fixed and dilated pupilsdilated pupilsusually seen with severe hypoxia.• Fixed pupils are typically seen withbarbiturate overdose.• Brainstem injury presents with pupilsfixed bilaterally in the midposition.
DISORDERS OF THE RETINALDISORDERS OF THE RETINALBLOOD SUPPLYBLOOD SUPPLY■ The blood supply for theretina is derived fromthe central retinalartery, which suppliesblood flow for theentire inside of theretina, and fromvessels in the choroid,which supply the rodsand cones.■ Central retinal occlusioninterrupts blood flow tothe inner retina andresults in unilateralblindness.■ The retinopathies,which are disorders ofthe retinal vessels,interrupt blood flow tothe visual receptors,leading to visualimpairment.■ Retinal detachmentseparates the visualreceptors from thechoroid, whichprovides their majorblood supply.Fundus of the eyeas seen in retinalexamination with anophthalmoscope:(left) normalfundus; (middle)diabetic retinopathy—combination ofmicroaneurysms,deep hemorrhages,and hard exudatesof backgroundretinopathy; (right)hypertensiveretinopathy withpurulent exudates.Some exudates arescattered, whileothers radiate fromthe fovea to form amacular star.
DISORDERS OFDISORDERS OFTHE MIDDLE EARTHE MIDDLE EAR■■ The middle ear is a small air-filledThe middle ear is a small air-filledcompartment incompartment in the temporal bone.the temporal bone.It is separated from the outer earIt is separated from the outer earby the tympanic membrane,by the tympanic membrane,contains tiny bony ossiclescontains tiny bony ossicles that aidthat aidin the amplification andin the amplification andtransmission oftransmission of sound to the innersound to the innerear, and is ventilated by theear, and is ventilated by theeustachian tube, which iseustachian tube, which isconnected to theconnected to the nasopharynx.nasopharynx.■■ The eustachian tube, which is lined with a mucousThe eustachian tube, which is lined with a mucous membrane that ismembrane that iscontinuous with the nasopharynx,continuous with the nasopharynx, provides a passageway forprovides a passageway forpathogens 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, usuallyassociated with an acute infectionassociated with an acute infection (acute OM) or an accumulation of(acute OM) or an accumulation offluid (OME). Itfluid (OME). It commonly is associated with disorders of eustachiancommonly is associated with disorders of eustachiantube function.tube function.■■ Impaired conduction of sound waves and hearingImpaired conduction of sound waves and hearing loss occur when theloss occur when thetympanic membrane has beentympanic membrane has been perforated; air in the middle ear hasperforated; air in the middle ear hasbeen replacedbeen replaced with fluid (OME); or the function of the bonywith fluid (OME); or the function of the bony ossicles hasossicles hasbeen impaired (otosclerosis).been impaired (otosclerosis).
HEARING LOSSHEARING LOSS■ Hearing loss representsimpairment of the abilityto detect and perceivesound.■ Conductive hearing loss iscaused by disorders inwhich auditory stimuli arenot transmitted throughthe structures of the outerand middle ears to thesensory receptors in theinner ear.■ Sensorineural hearingloss is caused bydisorders that affect theinner ear, auditory nerve,or auditory pathways.
Diseases of the Basal GangliaDiseases of the Basal Ganglia The basal ganglia areThe basal ganglia aremade up of:made up of: –– thethe corpus striatumcorpus striatum(consisting of the(consisting of the caudatecaudatenucleusnucleus and theand theputamenputamen);); –– the inner and outerthe inner and outerglobus pallidusglobus pallidus(pallidum, consisting of an(pallidum, consisting of aninternal and an externalinternal and an externalpart);part); –– thethe subthalamicsubthalamicnucleusnucleus; and; and –– thethe substantia nigrasubstantia nigra(pars reticulata [p. r.] and(pars reticulata [p. r.] andpars compacta [p. c.]).pars compacta [p. c.]). TheirTheir functionfunction is mainlyis mainlyto control movement into control movement inconjunction with theconjunction with thecerebellum,motor cortex,cerebellum,motor cortex,corticospinal tracts, andcorticospinal tracts, andmotor nuclei in the brainmotor nuclei in the brainstem.stem.
Parkinson’s Disease Parkinson’s disease is a diseaseParkinson’s disease is a diseaseof the substantia nigra (p. c.)of the substantia nigra (p. c.)which via dopaminergic tractswhich via dopaminergic tractsinfluences GABAergic cells in theinfluences GABAergic cells in thecorpus striatum. Thecorpus striatum. The causecause isisfrequently afrequently a hereditary dispositionhereditary dispositionthat in middle to old age leads tothat in middle to old age leads todegeneration of dopaminergicdegeneration of dopaminergicneurons 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 andandpoisoningpoisoning (especially by CO,(especially by CO,manganese, and 1-methyl-4-manganese, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinephenyl-1,2,3,6-tetrahydropyridine[MPTP], which was once used as[MPTP], which was once used asa substitute for heroin). The cella substitute for heroin). The celldestruction probably occurs partlydestruction probably occurs partlyby apoptosis; superoxides areby apoptosis; superoxides arethought to play a causal role. Forthought to play a causal role. Forsymptoms to occur, over 70% ofsymptoms to occur, over 70% ofneurons 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 substantianigra (p. c.) decreases thenigra (p. c.) decreases thecorrespondingcorresponding dopaminergicdopaminergicinnervationinnervation of the striatum.of the striatum.
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