Adapted from Text taken from
http://www.kumc.edu/AMA-MSS/study/neuro4.htm

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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.


Chart Decription of Fiber Types


CLASS DIAMETER
VELOCITY		 ELECTRICAL
STIMULATION		 SENSATION
II (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


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.


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: area of skin, that when appropriately stiumulate, causes neuron 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:
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.


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 Sub. 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 V of 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 LEWIS (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.