THE CEREBELLUM AND BASAL GANGLIA
CEREBELLAR FIBERS AND CELL TYPES: - AFFERENT FIBERS:
- MOSSY FIBERS: They make excitatory synapses with Granule Cells. They will ultimately influence a large number of Purkinje Cells via the Granule Cell output.
- They receive input from all incoming sources except the Inferior Olive:
- Spinocerebellar Tract (motor info about the extremities)
- Pontine Nuclei (motor info about the head and neck)
- They will send collaterals to the Deep Cerebellar Nuclei, as well as to the Granule Cells
- CLIMBING FIBERS: They make powerful, obligatory excitatory synapses on a very SMALL NUMBER of Purkinje Cells
- They all originate from the Inferior Olivary Nucleus
- They all will send collaterals to the Deep Cerebellar Nuclei directly, as well as to the Purkinje Cells.
- GRANULE CELLS, also called PARALLEL FIBERS, are strictly within the cerebellum, in the folia. They are interneurons in the cerebellar circuit.
- They make excitatory synapses with a LARGE NUMBER of Purkinje Cells
- They are called parallel fibers because their fibers run parallel to the folia (folds) of the cerebellar hemispheres.
- Granule cells will also send excitatory signals to the following inhibitory interneurons:
- Basket Cells: They will in turn inhibit Purkinje Cells
- Stellate Cells: They will in turn inhibit Purkinje Cells
- Golgi Cells: They will provide negative feedback and inhibit the Granule Cells
- PURKINJE CELLS: EFFERENT FIBERS
- They are the only "efferent" fibers in the cerebellar cortex. They will make synapses on the Deep Cerebellar Nuclei ------> transmit info to the rest of the CNS.
- Purkinje cell input onto the Deep Cerebellar Nuclei is always inhibitory, using neurotransmitter GABA.
- DEEP CEREBELLAR NUCLEI: They will project to Thalamus ------> excitatory connection to Motor Cortex ------> excitatory influence on descending systems.
- FNXNS:
- Receives excitatory collateral branches from Mossy fibers and Climbing Fibers.
- Receives inhibitory tonal input from Purkinje Cells.
- Deep Cerebellar Nuclei have a high background firing rate, thus Purkinje Cell inhibitory input is modulated.
- NUCLEI:
- FASTIGIAL NUCLEUS: Medial-most
- INTERPOSITUS NUCLEUS: Middle o' the road
- DENTATE NUCLEUS: Lateral-most
VESTIBULOCEREBELLUM: Archicerebellum. - STRUCTURE: FLOCCULONODULAR LOBE is the small lobe on the posterior inferior aspect of cerebellum. It modulates VOR and Postural Reflexes.
- FNXNS:
- MODULATE VESTIBULO-POSTURAL REFLEX: Cerebellum does fine tuning of postural reflexes, adjusting the magnitude, strength, and range of movement.
- PATHWAY: VIII Nerve Afferents--> Mossy Fibers to the Cerebellum ------> Fastigial Deep Nucleus ++ Vestibular Nucleus ------> Reticulospinal + Vestibulospinal Tracts ------> influence alpha-motor neurons.
- Excitatory signals to Vestibulospinal will excite (modulate) the extensors.
- Excitatory signals to Reticulospinal will excite (modulate) the flexors.
- Fastigial Nucleus does the calculations for these adjustments, although some fibers also go directly to the descending tracts without going through fastigial nucleus.
- SUPPRESS VOR REFLEX: If you want to follow a moving an object while moving your head too, then you don't want the VOR reflex to move your eyes. Under these circumstances the vestibulocerebellum will supress that reflex.
- PATHWAY: VIIIth Nerve collateral afferents enter cerebellum as Mossy Fibers ------> Excite Granule Cells in cerebellum ------> Excite Purkinje Cells ------> Inhibition of Vestibular Nucleus ------> Cancel or modulate excitatory input from VIIIth afferents.
- Note that the VIIIth nerve is still firing to activate the VOR reflex. The only difference is that now the end-signal is being canceled (or lessened) by the cerebellar input.
- ADJUST REFLEX GAIN: If you put on reversing prisms (which reverse the movement of the visual field), your VOR reflex will compensate for the new visual input within a few days. This change in the VOR reflex is dependent on the Cerebellum and Inferior Olive.
- LESIONS: Can be caused by a medulloblastoma in children, or by chronic alcoholism. It will produce two defects:
- Nystagmus is produced from unmodulated VOR reflex.
- Disequilibrium, an inability to maintain posture, from unmodulated postural reflexes.
- REPAIR SHOP THEORY: Based on reversing prisms experiments and others, this theory says that the cerebellum is responsible for continually responding to the changing behavior of neurons with regard to voluntary movements and reflexes.
SPINOCEREBELLUM: Paleocerebellum - STRUCTURES
- VERMIS: Midline structure, receives input from Vestibular Nuclei and Spinocerebellar Tract.
- PARAVERMIS: On either side, receives input only from Spinocerebellar Tract.
- FNXN: Continual correction of movements, comparing actual motor movement with motor cortex "intentions" of movement.
- INPUT: Spinocerebellum receives input from motor cortex and spinocerebellar tract.
- It then reconciles those signals with each other (actual action reconciled with intended action), and issues a correction factor.
- OUTPUT:
- Vermis ------> Fastigial Nucleus + Vestibular Nucleus ------> Descending Extrapyramidal Tracts
- Paravermis ------> Fastigial Nucleus + Interpositus Nucleus ------> Descending Extrapyramidal Tracts
- SOMATOTOPIC ORGANIZATION: The spinocerebellum has somatotopic organization with regard to the regions of the body it is "comparing." Head and neck is generally nearest the center, with extremities in the periphery.
CEREBROCEREBELLUM: Neocerebellum - STRUCTURE: The large lateral hemispheres that make up most of the cerebellum.
- FNXN: Programming of repeated movements. Calculating the "metrics" of movements, such as reaching for an object in space. We don't consciously think about these details of conscious movement.
- INPUT: Pontine Nuclei from Cerebral Cortex.
- OUTPUT: Dentate Nucleus ------> Thalamus ------> Motor Cortex
- PATHWAY of MODULATION: Limbic System initiates the drive or desire to move
- Limbic System ------> Frontal Cortex (conscious or subconscious judgment and intention) ------> Pontine Nuclei ------> Cerebellum ------> Dentate Nucleus ------> Thalamus ------> Motor Cortexx ------> movement is executed
- LESION: CEREBELLAR SYNDROME. This is a lesion of both Spinocerebellum and Cerebrocerebellum, as there is rarely (i.e. never) a lesion of only one or the other.
- Hypotonia: From reduced gamma neuron activity, due to loss of extrapyramidal excitatory input.
- Ataxia, Asynergia: Lack of coordinated movement. Most important, errors in METRICS of movement (reaching arm too far or too close to target)
- INTENTION TREMOR, Dysmetria: A problem terminating movements, or a tremor that only present when moving. This is different than Resting Tremor which occurs with Parkinson's.
- Adiadochokinesis: Inability to make rapid alternating movements, such as pronation and supination of hand.
- LESION: IPSILATERAL DEFICIT. All lesions of the cerebellum produce ipsilateral deficit because the system is double-crossed.
- Deep Nuclei cross the midline to opposite motor cortex.
- Upper motor neurons cross again through pyramidal decussation.
BASAL GANGLIA: Components - STRIATUM: Uses GABA as inhibitory transmitter; it projects to ------> Globus Pallidus to have inhibitory influence.
- GLOBUS PALLIDUS:
- It receives inhibitory input from the Corpus Striatum.
- Some of these inhibitory fibers carry GABA and Substance P as transmitters. These act on the GPi and are inhibitory.
- Other inhibitory fibers carry GABA and Enkephalins as transmitters. The pathway of these signals:
- Corpus Striatum ------> GPe ------> Subthalamic Nucleus ------> GPi
- FNXN: It projects inhibitory neurons to the thalamus to modulate motor function.
- Loss of this inhibition will result in Hemiballismus.
- INTERNAL SEGMENT (GPi): It is functionally continuous with the Substantia Nigra, Pars Reticularis (SNr)
- FNXN: Along with the SNr, it is the OUTPUT NUCLEUS of the Basal Ganglia. The GPi normally inhibits the Thalamus (via GABA).
- In Parkinson's Disease, it is overactive.
- SOMATOTOPIC ORGANIZATION: Continuous with the SNr, its output goes to the limbs.
- EXTERNAL SEGMENT (GPe)
- SUBTHALAMIC NUCLEUS: The subthalamic nucleus normally stimulates the GPi.
- In Parkinson's Disease, it is overactive.
- In Huntington's and Hemiballismus, it is underactive.
- SUBSTANTIA NIGRA
- PARS RETICULARE (SNr): Ventral part of the Substantia Nigra. It is functionally continuous with the Internal Globus Pallidus (GPi)
- FNXN: Along with the SNr, it is the OUTPUT NUCLEUS of the Basal Ganglia.
- SOMATOTOPIC ORGANIZATION: Continuous with the GPi, its output goes to the head and neck.
- PARS COMPACTA (SNc): Dopamine-containing neurons.
- NIGROSTRIATAL TRACT: Substantia Nigra, Pars Compacta releases Dopamine. Dopamine acts on the Corpus Striatum and has both inhibitory and excitatory effects, depending on the connection.
- CIRCUIT: SNc ------> excitatory on Striatum ------> (Substance P) Inhibitory on GPi ------> result is inhibition of Thalamic projections ------> Cerebral cortex doesn't receive the Thalamic projections.
- CIRCUIT: SNc ------> inhibitory on Striatum ------> (Enkephalins) inhibitory on GPe ------> inhibitory to Subthalamic Nucleus ------> GPi ------> result is inhibition of Thalamic projections ------> Cerebral Cortex doesn't receive the Thalamic projections.
- BASAL GANGLIA Basic Circuitry: Cerebral Cortex ------> Striatum ------> GPi + SNr ------> Thalamus ------> Motor cortical output
PARKINSON'S DISEASE: A lesion of the Dopamine-containing Nigrostriatal Tract, producing a dopamine deficit. - SYMPTOMS: Parkinson's Disease is a hypokinetic disorder.
- Lead Pipe Rigidity: Resistance to movement.
- RESTING TREMOR: To be distinguished from an intention tremor (as in Cerebellar Syndrome). This is a tremor when there is no movement.
- This tremor is of a lower frequency than corresponding Intention tremor.
- The tremor is better when in motion, so it is less debilitating than a moving tremor.
- Akinesia / Bradykinesia: Inability to initiate movement, or slow initiation of movement.
- This symptom responds well to treatment.
- Postural Instability
- Cognitive Problems
- ETIOLOGY: Deficiency of dopamine exerts its effects through two pathways. Both pathways ultimately result in over activity of the Globus Pallidus Interna ------> Over suppression of Thalamus ------> fewer thalamic projections to the Motor Cortex.
- In Parkinson's Disease, the subthalamic nucleus is overactive.
- Dopamine can get to 20% below normal before Parkinsonian symptoms will occur.
- PROGRESSION OF DISEASE: Cognitive loss and eventual death from respiratory failure.
- TREATMENT:
- L-DOPA is drug of choice.
- CONVERSION: L-DOPA is a Dopamine precursor that can get through the blood-brain barrier. It is converted to Dopamine by DOPA-Decarboxylase once in the brain.
- CARBIDOPA: This is always given with L-DOPA. It is a DOPA-Decarboxylase Inhibitor which blocks conversion of L-DOPA ------> Dopamine in the periphery.
- SIDE-EFFECTS:
- ON-OFF Phenomenon: Suddenly therapy is ineffective, periodically.
- Freezing Phenomenon: All of the sudden become rigid and stop, unable to initiate movement.
- The drug becomes less effective with long-term use.
- Dyskinesias: Involuntary movements (another form of tremors, hyperkinetic) result from the excessive dopamine.
- THALAMOTOMY: Surgical lesion of Ventral Lateral Thalamus, for the treatment of tremors. this surgery does not alleviate the original problem, so it is only symptomatic treatment.
- CANDIDATES: People who don't respond well to L-DOPA (~10%), have terrible side-effects with L-DOPA, or who have debilitating tremors.
- Must have no cognitive deficiencies and be able to respond well to surgery.
- ELECTRO-STIMULATION OF THALAMUS: Surgically implant an electrode on the Thalamus and another in the chest. Then use a magnet to stimulate thalamus periodically and INHIBIT it.
- This is a surgical alternative to outright Thalamotomy, leaving the VL Thalamus intact and only inhibiting it as necessary.
- PALLIDOTOMY: Surgical lesion of Globus Pallidus Interna. This surgery has been shown to be the most effective.
- CANDIDATES: Pretty much the same as for thalamotomy.
- RISKS: Loss of visual field, because the GPi is very close to Optic Tract.
- ELECTROSTIMULATION is on the horizon, and currently experimental at KUMC.
- HISTORICAL STUFF:
- Stereotactic Surgery: Early attempts to place a brain lesion in specific place, using a pineal calcification (on a skull film) as a reference point.
HUNTINGTON'S CHOREA: Lesion of the Corpus Striatum, involving GABA and Enkephalin neurons - ETIOLOGY: Loss of Corpus Striatum GABA/Enk neurons ------> Disinhibition of the Globus Pallidus Externa ------> Excessive inhibition of the Subthalamic Nucleus.
- The subthalamic nucleus is deficient
- SYMPTOMS: Huntington's is a hyperkinetic disorder.
- The result is a lesion similar to the effects of a Subthalamic Nucleus lesion (i.e. Hemi-ballismus).
HEMIBALLISMUS: Lesion of Subthalamic Nucleus, ruins the GPi inhibitory neurons that project to the thalamus ------> over excitation. - SYMPTOM: Violent, involuntary movement of contralateral limb.
- ETIOLOGY: Usually created be a vascular lesion (stroke) specific to the Subthalamic Nucleus.
- The subthalamic nucleus is deficient
- SOMATIC SENSATION
TRANSDUCTION: The process by which a physical stimulus is converted into a neural signal and sent to the CNS.- Trigger Zone: The threshold of stimulus, in the sensory receptor, at which an action potential is generated. Some sensory receptors are more sensitive than others.
- MODALITY SPECIFICITY: Any particular sensory unit is most sensitive to only one modality.
- There are four broad classes of somatic stimuli:
- Tactile Sensation (Pressure, Cold)
- Proprioception (body position and movement)
- Thermosensation
- Pain
- The modality to which a receptor it is sensitive is called the adequate stimulus for the receptor.
- The specific modality is the one that triggers the receptor at the lowest threshold potential. Other modalities may also trigger the receptor, but at much high potentials.
- Paradoxical Cold is an exception to the Modality Specificity rule.
- Sometimes heat may be perceived as cold, because it triggers cold fibers rather than warm fibers.
- Normally warm fibers are triggered by an increase in temperature, and cold fibers by a decrease in temperature.
FIBER DIAMETER AND MODALITY SPECIFICITY:- Class II (A-beta) Fibers: Cutaneous Sensation
- Fibers terminate in specialized nerve endings such as Merckel's Disks and Pacinian Corpuscles.
- ASPHYXIA: These fibers are most sensitive to asphyxia and to physical insult, because they are the largest of the sensory fibers.
- Anesthesia: These fibers are the last to be blocked by anesthesia -- they are the largest fibers.
- Class III (A-delta) Fibers: Fast Pain, crude touch, temperature sensation.
- Fibers terminate in free nerve endings.
- FAST PAIN: Pin-prick pain; it is the first pain you will feel when pricking your finger.
- These fibers are sensitive to intense mechanical stimulation (such as a puncture) and temperature.
- Purpose = these fibers cause us to quickly withdraw away from a dangerous stimulus.
- Class IV (C) Fibers: Slow Pain, crude touch, temperature sensation.
- Fibers terminate in free nerve endings.
- SLOW PAIN: Throbbing pain, which evokes the troublesome affective experience of pain.
- These fibers are respond to visceral noxious stimuli -- either mechanical, heat, or chemical.
- Purpose = these fibers cause us to immobilize the body part so it can heal.
- ANESTHESIA: Slow pain fibers are the most sensitive to local anesthesia. Anesthesia blocks small-diameter fibers before large-diameter.
- Asphyxia: These fibers are the last to be blocked by asphyxia, as they are the smallest fibers.
CLASSDIAMETER VELOCITY
ELECTRICAL STIMULATION
SENSATIONII (A-beta)Relatively large diameter Fast conduction velocity
Lowest
threshold i.e. first to be stimulated
Cutaneous Sensation III (A-delta)Small diameter Slow conduction velocity
Medium threshold
Fast Pain
Crude Touch Some temperature
IV (C)Smallest diameter Slowest conduction velocity
Highest
threshold i.e. last to be stimulated
Slow Pain
Crude Touch Some temperature
FREE NERVE ENDINGS: Pain and temperature both end in free nerve-endings in the skin.
SPECIALIZED NERVE ENDINGS: They mediate tactile sensation: flutter, vibrations, and pressure.- MEISSNER'S CORPUSCLES: They mediate the sensation of flutter -- localized, slow vibrations.
- Rapidly-Adapting, Phasic response: The receptor shows Adaptation in that it stops firing after the same stimulus has been present for a while. It "blocks" out the stimulus once the stimulus becomes old news.
- Anatomical Distribution: Found in Glabrous (non-hairy) skin, as in palm of hands.
- The nerve fiber loses its myelin sheath before entering the corpuscle.
- Serves the same purpose that hair follicles serve in hairy skin, i.e. sensation of flutter.
- PACINIAN CORPUSCLES: They mediate the sensation of vibration.
- Rapidly-Adapting, Phasic response: The receptor stops firing after the stimulus has been present for a while.
- STRUCTURE: It is like an onion.
- If you remove the layers of the onion, then the receptor becomes slowly-adapting. The onion-layers thus serve the purpose of adaptation -- they make it so the underlying nerve fiber is only discharged temporarily.
- The onion layers also filter out the low-frequency stimuli, such that Pacinian Corpuscle has frequency specificity for high frequency vibrations.
- MECKEL'S DISKS: Mediate sensitivity to pressure.
- Slowly-adapting, Tonic response. The nerve continues to discharge as long as the stimulus remains. So, you continue to feel pressure as long as the pressure is still there.
ADAPTATION: "A decrease in neural response to sustained stimulation." Meissner's and Pacinian corpuscles both show adaptation.- PHASIC RESPONSE refers to the fact that the receptor will fire only when there is a change in stimulation.
- TONIC RESPONSE: Refers to continual firing of the receptor when a continual stimulus is present. No change in stimulus is necessary to maintain firing.
DORSAL-COLUMN MEDIAL-LEMNISCAL PATHWAY: Proprioception and Discriminative Touch run parallel with each other but actually have separately named paths.- PATHWAYS: For spinal components (not trigeminal). These fibers enter through the medial branches of the Dorsal Horn.
- DISCRIMINATIVE TOUCH: Discriminative Touch fibers are Group II (A-beta) fibers.
- First-Order: Nucleus Gracilis (medial, S4-T5) and Cuneatus (Lateral, C1-T4) carry first-order neurons.
- Thalamic Relay: VPL, Ventral Posterolateral Nucleus of Thalamus.
- Somatosensory Cortex: Area 3b
- So, Area 3B receives 3rd-order neurons originating from specialized receptors (Meckel's Disks), via Group II fibers
- PROPRIOCEPTION: Conscious Proprioception receptors are 1A-SPINDLE FIBERS
- Evidence: Joint position and movement can still be perceived following anesthesia to the joint capsule or following replacement with a prosthetic joint. Thus, the proprioception fibers don't lie within the joint.
- First-Order: Nucleus Z (S4-T5) and External Cuneate Nucleus (C1-T4)
- Thalamic Relay: VPS, VENTRAL POSTERIOR SUPERIOR Nucleus of Thalamus.
- Somatosensory Cortex: Area 3a
- So, Area 3A receives IIA Spindle Afferents for proprioception signal.
- SOMATOTOPIC ORGANIZATION
- Spinal Cord: Sacral is most medial and Cervical is most lateral. As you move up the cord, sacral segments enter the cord first, and higher up segments enter right "on top of," i.e. lateral to, the sacral segments.
- THALAMUS: Somatotopic Organization is essential reversed.
- VPM: Trigeminal, i.e. head, is most medial in medial nucleus.
- VPL: Spinal is more lateral.
- VPS: The VPS lies above both of the other nuclei, and it maintains the organization of head = medial, and sacral = lateral
- SOMATOSENSORY CORTEX: There are four relatively complete maps of the body: 3a, 3b, 1, and 2.
- Sacral (lower body) is most medial, at the top of the somatosensory cortex.
- Cervical (upper body) is most lateral, at the temporal pole of the somatosensory cortex.
- DISTORTED REPRESENTATION: Finger tips, lips, and tongue get a disproportionate amount of cortex, because they are the most sensitive sensory organs.
- DESCENDING SENSORY Connection: Descending Sensory fibers go from Sensory Cortex ------> Thalamus ------> Dorsal Column Nuclei. They may serve a role in adaptation or filtering repetitive stimuli, but function is unsure.
- LESIONS:
- Tabes Dorsalis: Secondary to Syphilis; lesion of dorsal columns. Patients show deficits in proprioception and discriminative touch, but not pain and temp.
- Transection of Dorsal Columns: Results in large increase in two-point discrimination.
- Destruction of S1 (Somatosensory Cortex): Expected sensory deficits result.
Labelled Line Theory: There are separate pathways for each modality of sensation, and these all run into the CNS in a parallel fashion.- CORTICAL COLUMNS: Each column contains layers that represent different modalities, but they all came from the same region of the body.
- So, neurons in the same "layer" or lamina of the cortex will exhibit the same modality specificity.
RECEPTIVE FIELDS: The area of skin which, when appropriately stimulated, causes a neuron to discharge.- The smaller the receptive field, the more sensitive is the sensory ability. Smaller receptive fields mean higher acuity.
- Proprioceptive and Discriminative Touch (DC-ML) fibers have smaller receptive fields than pain and temp (anterolateral) fibers.
- TWO-POINT THRESHOLD: The minimum distance, on the skin, at which two pin-points can be distinguished. The smaller the two-point threshold, the higher the tactile acuity.
- Fingertips and lips have smallest two-point-thresholds (~2 mm), while trunk has much larger threshold (~60 mm)
- Small receptive fields correspond to high innervation density and a disproportionately large amount of somatosensory tissue in the CNS.
PHANTOM LIMB SYNDROME: People who have had a severed limb still retain sensation that the limb is there (proprioception) when other parts of the body are stimulated, such as the face.- This is due to plasticity of neurons in the CNS. The CNS neurons that used to supply the missing limb are near the face, so they can get stimulated when face is stimulated.
HIERARCHICAL PROCESSING: As one ascends through the CNS, more complex types of sensations are processed.- Area 3a and 3b (aka S1) are the first recipients of sensory information.
- Area 1 and 2 (aka S2 (?)) receive input from Areas 3a and 3b. Thus 1 and 2 are higher up in the processing of somatic sensation.
- For example, Areas 1 and 2 can discriminate selectivity of movement of a finger across the skin, whereas area 3 cannot.
- AREA 2: It is unique in that it receives a convergence of multiple modalities. Both Proprioceptive and Tactile input can arrive at the same fibers.
- This convergence of function allows for Area 2 to perform Stereognosis (identifying objects by touch). Area 2 lesion results in severe deficit in this specific ability.
NEGLECT SYNDROME: Lesion of posterior Tempero-parietal area. Extinction occurs in the Neglect Syndrome. Extinction is failure to recognize a specific stimulus (either visual, somatic, and/or auditory) on one side of the body, contralateral to the lesion.
PAIN:- Terms:
- Nociceptive Stimuli: Stimuli that produce pain.
- Analgesia: A condition in which nociceptive stimuli are not perceived as painful.
- Two components of Pain: The two components of pain are separable by drugs.
- The sensation of pain itself.
- The affective component of pain in which it is perceived to be painful or unpleasant.
- Morphine separates these two components such that patients still feel the pain but they do not find it to be unpleasant or "painful."
- PAIN-PRODUCING STIMULI (PPS): Chemicals that are involved in transduction of slow-pain fibers.
- POTASSIUM: High extracellular K+ is indicative of tissue damage and is therefore painful.
- BRADYKININS: Tissue injury ------> proteolytic enzymes into the extracellular fluid ------> react with gamma globulins to create Bradykinins.
- Bradykinin is one of the most painful substances known. It activates C-Fiber terminals.
- Bradykinins causes vasodilation.
- Bradykinins causes the production of Prostaglandin E2 (PGE2), which serves to enhance the sensitivity of painful C-Fibers.
- Aspirin will block this prostaglandin synthesis, wouldn't ya know??
- HISTAMINE: Substance-P, released by C-fibers, causes Mast Cells to release Histamine.
- Histamine can also activate C-fiber terminals.
- Neurotransmitters used in Anterolateral System:
- GROUP III (A-delta) NEUROTRANSMITTER: Glutamate
- GROUP IV (C-FIBER) NEUROTRANSMITTERS: C-Fibers have two neurotransmitters which cause vasodilation when released on vessels.
- Substance-P: Increases capillary permeability, perhaps via NO.
- Calcium Gene-Related Peptide (CGRP): It enhances the vasodilatory effects of Substance-P.
- ANTEROLATERAL SYSTEM PATH:: Group-III (Fast Pain) and IV (slow-Pain) fibers enter the spinal cord through the lateral portion of the Dorsal Root over the Tract of Lissauer ------> Ascend one or two segments ------> Synapse in Substantia Gelatinosa ------> CROSS ------> Ascend in Anterolateral tract.
- NEOSPINOTHALAMIC PATHWAY: Fast pain (III) and temperature sensation.
- Second order neurons terminate in the VPL of Thalamus.
- These neurons are modality specific, have high thresholds of stimulation, and have small receptive fields -- all things expected for fast, sharp, localized pain.
- MARGINAL ZONE: Lamina I and Vof the Dorsal Horn. This is the outermost and innermost layers of the Anterolateral System.
- Fast Pain only goes through the Marginal Zone.
- The fibers split into layers in the Tract of Lissauer.
- PALEOSPINOTHALAMIC PATHWAY: Receives Slow-Pain (IV) fibers, plus some Fast-Pain.
- Second order neurons terminate in Intralaminar Nuclei of Thalamus.
- Lesion of the Intralaminar Nuclei will relieve chronic pain.
- These fibers mediate, chronic deep pain, but not cutaneous pain.
- Lamina II and III carry the Slow Pain fibers -- the middle two layers of Anterolateral System.
- Anterolateral Cordotomy: Sectioning the anterolateral cord on the contralateral side in order to relieve intractable pain.
- Targets of Anterolateral Pathway:
- Spinoreticular Pathway: Also for modulation of pain (see below)
- Spinotectal Pathway: Also involved in pain control; orientates our response to painful stimuli.
- Spinothalamic Pathway: The primary pathway for pain transmission to Thalamus.
TRIPLE RESPONSE OF ***** (AXON REFLEX):- Wheal: Localized raised area resulting from vasodilation from local irritants.
- Flare: Reddened area surrounding the wheal.
- It is a axon-axon reflex that does not go through the CNS. Local Nociceptive fibers are stimulated, and they send messages to neighboring fibers to cause a "flare" of vasodilation around the original wheal.
- Capsaicin is a peppery substance that causes the wheal-and-flare response locally. Applied continually, it will desensitize the C-Fibers to local allergens and can thus be used as a topical analgesic.
- HYPERALGESIA: Enhanced sensitivity to pain occurs in the region following the Wheal and Flare response.
THALAMIC (CENTRAL PAIN) SYNDROME: Spontaneous pain, and exaggerated responses to pain stimuli, resulting from a vascular lesion in the Thalamus.- Triad of related symptoms:
- Spontaneous Pain
- Non-Injurious stimuli (light touch, movement) are perceived as painful.
- Hyperalgesia: aggravated pain response.
- Originally, it was thought that only the Thalamus produced these symptoms, but it is now known that a lesion anywhere along the pain pathway (such as anterolateral cordotomy) can produce the symptoms.
Mechanisms of ANALGESIA:- GATE CONTROL THEORY: Transmission of pain information can be modified by descending CNS large-fibers. Endogenous activity in large-fiber pathways can block pain.
- After you bump your head, rubbing it can help it. When you rub your head you are stimulating large fiber pathways.
- Spinotectal and Spinoreticular Pathways: These are ascending pathways that in turn lead to inhibition of pain transmission in the dorsal horn. These pathways are an endogenous way of modulating pain.
- Alternative pathway for pain fibers: Nociceptive stimuli ------> Periaqueductal Gray of Midbrain and Periventricular Gray of Thalamus ------> Nucleus Raphe Magnus of the Reticular Formation.
- Serotonergic Pathway:From Nucleus Raphe Magnus the signal goes back down to Dorsal Horn of Spinal Cord ------> synapse with interneuron in Substantia Gelatinosa at all levels ------> inhibit the pain signal at the point of entry into the spinal cord.
- Noradrenergic Pathway: There is also a Noradrenergic pathway that has a modulatory effect on pain.
- Stimulus0Produced Analgesia can occur from electrical stimulation of the periaqueductal gray. Again, this analgesia has its effect by inhibiting pain transmission in Dorsal Horn.
- OPIOIDS:
- Inject very small amount of Morphine into one of two CNS regions to cause profound Analgesia:
- Periaqueductal Gray
- Dorsal Horn
- Opioid Receptors: Enkephalins and Endorphins are the endogenous ligands for these receptors. Opiates also bind to them but with higher potency.
- Opioid -Receptors are found in Periaqueductal Gray.
- Naloxone is an antagonist to this receptor.
- STRESS-INDUCED ANALGESIA: Extreme stress (Epinephrine) can induce analgesia so that a person can perform actions that would normally be painful. The action is not perceived as painful until after the stressful event is over.
RADICULAR PAIN: Pain localized to the dermatome of a dorsal root.- Injury to a single Dorsal Root will not usually produce Anesthesia, because there is overlap between dermatomes.
- Paresthesia (tingling, etc.) is common however, and Radicular Pain often occurs with Paresthesia.
REFERRED PAIN: Visceral injury will send afferent pain information on the same nerves that also serve a cutaneous region. Because the brain is more used to getting sensory input from the cutaneous region of the nerve, the CNS will interpret the pain as originating from the cutaneous region.
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