Lecture I: Sensory Physiology

Question 1

What are the two classification schemes by which peripheral nerves are classified?

Answer 1

1) Their contribution to a compound action potential (A, B, and C waves)
2) Based on fiber diameter, myelin thickness, and conduction velocity (classes I, II, III, IV)

Question 2

What are the features of the group Ia or Aα peripheral axons (i.e., fiber diameter, myelination conduction velocity, and receptor supplied)?

Answer 2

• 13-20 μm (large)
• 80-120 m/s (fast)
• Heavily myelinated
• Receptor supplied: primary muscle spindles, Golgi tendon organs

*These are the alpha-motorneurons

Question 3

What are the features of the group IV or C peripheral axons (i.e., fiber diameter, myelination, conduction velocity, and receptor supplied)?

Answer 3

• 0.2-1.5 μm (small)
• 0.5-2 m/s (slow)
• Unmyelinated
• Receptor supplied: skin mechanoreceptors, thermal receptors, and nociceptors (slow pain)

Question 4

An appropriate stimulus applied to a somatosensory receptor produces a ________ that, when large enough, leads to action potentials that can be carried over a considerable distance into the CNS.

Answer 4

An appropriate stimulus applied to a somatosensory receptor produces a generator potential that, when large enough, leads to action potentials that can be carried over a considerable distance into the CNS.

Question 5

What is the Weber-Fechner Law; how much stimulus required for noticeable difference?

Answer 5

• There exists a logarithmic relationship between stimulus and perception
• A 10% difference is usually required for conscious perception of change

Question 6

How does perceived intensity differ amongst muscles and cutaneous stimuli?

Answer 6

• Muscle perceived intensity matches the actual intensity very closely
• Cutaneous perceived intensity may diverge from the actual intensity substantially

Question 7

When a stimulus persists unchanged for several minutes without a change in position or amplitude, what occurs to the neural response and sensation; this is called what?

Answer 7

• The neural response diminishes and sensation is lost
• This is receptor adaptation

Question 8

Receptors that respond to prolonged and constant stimulation are classified as?

Answer 8

Slowly adapting receptors

Question 9

Receptors that respond only at the beginning or end of a stimulus are classified how; what activates them?

Answer 9

• Rapidly adapting receptors
• Only active when the stimulus intensity increases or decreases

Question 10

What are the 4 mechanoreceptors?

Answer 10

1. Meissner corpuscle
2. Pacinian corpuscle
3. Merkel disk
4. Ruffini ending

Question 11

What is a receptive field?

Answer 11

Individual mechanoreceptor fibers convey information from a limited area of skin

Question 12

Tactile acuity is highest and lowest where and how does this related to the size of the receptive field?

Answer 12

• Tactile acuity is highest in fingertips and lips (smallest receptive field)
• Tactile acuity is lowest in calf, back and thigh (largest receptive field)

Question 13

What is an afterdischarge?

Answer 13

• In some cases of receptor adaption, the removal of the stimulus triggers AP’s as the ending “reforms.”
• The persistance of a sensation after the stimulus eliciting the discharge has been removed

Question 14

What is Pre-synaptic inhibition; what kind of synapse; what is the end result?

Answer 14

• Axo-axonal synapse
• The post-synaptic cell is a pre-synaptic terminal
• The end result of pre-synaptic transmission is reduced NT released from the inhibited pre-synaptic terminal

Question 15

What are the 4 steps in pre-synaptic inhibiton (what’s released and the end result)?

Answer 15

1. Pre-synaptic terminal of neuron C synspases on the pre-synaptic terminal of neuron A, when acitvated neuron C releases GABA causing influx of Cl- into neuron A
2. Results in hyperpolarization of pre-synaptic terminal of neuron A
3. Less Ca²⁺ enters cytosol
4. Leads to less NT released and reduced probability of AP’s in neuron B

Question 16

Pre-synaptic inhibition occurs where in the pathways involved in central processing of the senses; what impact does it have on the brain?

Answer 16

• Occurs between neighboring receptors at the first synapse in their pathway
• Every synapse along the way represents a chance to modify or respond to the stimulus
• Increases the brain’s ability to localize the signal

Question 17

What is the most powerful form of inhibitory control in all primary afferent fibers?

Answer 17

Pre-synaptic inhibition

Question 18

The somatosensory cortex has how many layers, how are the neurons arranged, and what is the importance of this arrangement?

Answer 18

• Has 6 layers
• Arranged in columns
• Each column deals with one sensory modality in one part of the body

Question 19

Which layers of the primary sensory cortex houses the columns which are the main site of termination of axons from the thalamus?

Answer 19

Layer IV

Question 20

Which are the main output neurons from the primary sensory cortex?

Answer 20

Pyramidal cells

Question 21

Where is the primary somatosensory cortex (S1) located, which Brodmann’s areas, and what is this part of the brain involved in?

Answer 21

• Located in post-central gyrus
• Brodmann’s 1, 2, and 3
• First stop for most cutaneous senses
• Involved in the integration of information for postion sense as well as size, shape discrimination

Question 22

Where is the secondary somatosensory cortex (S2) located, whre does it receive input from and what is this part of the brain involved in?

Answer 22

• Wall of the sylvian fissure
• Receives input from S1
• Cognitive touch
• Comparisons between objects, different tactile sensations and determining whether something becomes a memory

Question 23

Do the primary and secondary somatosensory areas (S1 and S2) have somatotopic representation?

Answer 23

• S1 has detailed somatotopic representation
• S2 has somatopic representation, BUT is NOT as detailed as S1

Question 24

What is the function of the parieto-temporal-occipital (PTO) association cortex?

Answer 24

• High level interpretation of sensory inputs
• Receives input from multiple sensory areas, including S1 and S2
• Analyzes spatial coordinates of self in enviornment, names objects, and has many functions

Question 25

What are Corticofugal signals, where are they transmitted between and their function?

Answer 25

- Transmitted back from cortex to lower relay stations in the thalamus, medulla, or SC - Controls the intensity of sensory sensitivity - Typically **inhibitory** and **suppresses sensory input**

Question 26

What is the Doctrine of specific nerve energies, tells you what?

Answer 26

- No matter where along the afferent pathway is stimulated, the sensation that will occur is determined by the nature of the sensory receptor in the periphery connected to that pathway - Tells you the **modality** (i.e., what kind of receptor stimulated)

Question 27

What is the Law of Projections, tells you what?

Answer 27

- No matter where along the afferent path we stimulate, the **perceived** sensation is always referred back to the **area of the body** in which the receptor is located - Tells you where you feel it (**location**)

Question 28

What are the 4 ways pain can be characterized by location?

Answer 28

1) Deep pain (i.e., bone pain) 2) Muscle pain 3) Visceral pain 4) Somatic/cutaneous pain

Question 29

Nociceptors are bare nerve endings used for sensing noxious stimuli, what are the 2 types of fibers involved and characteristics of each?

Answer 29

**Aδ fibers:** small, sparsely myelinated. **Fast, sharp pain** **C fibers:** unmyelinated fibers associated with dull pain (**slow pain**)

Question 30

What are the different types of nociceptors (i.e., what are they sensitive to)?

Answer 30

- Sensitive to both **thermal** and **mechanical** stimuli (**majority**) - Sensitive only to **thermal** or only to **mechanical** - **Silent/sleeping:** not active during initial injury, but can be "woken up."

Question 31

Many mixed modality nociceptors express one of the \_\_\_\_\_\_family of receptors along with a mechanosensitive _____ channel.

Answer 31

Many mixed modality nociceptors express one of the **TRP** family of receptors along with a mechanosensitive **Na+** channel.

Question 32

Unlike other receptors, nociceptors express a number of ligand-gated receptors (in addition to the stimulus-gated channels), this includes receptors for what ligands?

Answer 32

- Substance P - The Kinins (i.e., bradykinin) - ATP - H+

Question 33

Mutations in which channel may lead to an absence of pain sensation or the production of a paroxysmal pain syndrome?

Answer 33

Na_v1.7 mechanosensitive Na+

Question 34

What are the TRP family of receptors?

Answer 34

- Transient receptor potential family of receptors (**TRPV1, TRPA1, TRPM8**) - Ligand-gated non-selective cation channel permeable to **Ca²⁺,** Na+, and/or K+

Question 35

When chemicals such as Substance P, Bradykinin, ATP, or H+ bind to a nociceptor how is sensitivity affected?

Answer 35

- They change the sensitivity of nociceptors (usually **increasing**) - Activate silent nociceptors

Question 36

What is the source of the Substance P, the Kinins, ATP, and H+ which act to bind nociceptors and alter the sensitivity?

Answer 36

- Activated nociceptors, the damaged tissue, and recruited WBC release these into the periphery as well as in the SC

Question 37

What is the NT released by Aδ fibers (for pain) in the SC and what receptor does it act on?

Answer 37

EAA which act on non-NMDA receptors

Question 38

What is the NT released by C fibers (for pain) in the SC and what receptor does it act on?

Answer 38

- Substance P and EAA's - Acts on both NMDA and non-NMDA receptors

Question 39

Nociceptors that travel with the spinoreticulothalamic pathway (slow pain) synapse where and then what?

Answer 39

Synapse on an **interneuron** in the SC before crossing and **ascending** to the **reticular formation**

Question 40

How are visceral afferents related to pain relayed to the brain; what do the additional synapses form?

Answer 40

- Travel with **autonomic nerves** - Have additional synapses within the **hypothalamus and medulla** - Form the basis of the **physiological** changes associated with visceral pain, including diaphoresis and altered BP

Question 41

What is the role of S1 and S2 in the central processing of pain?

Answer 41

Receive input from the nociceptors and play a **role** in **localizing pain**

Question 42

What is the role of the Insular Cortex in the central processing of pain?

Answer 42

- Particularly **important** in the interpretation of nociceptive inputs - Processes information about the **internal state of the body** - Contributes to the autonomic response to the pain **- Integrates ALL signals related to pain**

Question 43

In regards to pain what occurs with damage to the insular cortex?

Answer 43

- Asymbolia - Patient **will still feel pain** and can localize the pain, but **will lose the negative/emotional experience** of pain

Question 44

What is the importance of many nociceptive inputs going to the amygdala?

Answer 44

- Important for activating/producing the **emotional components** inherent in the sensation of pain - Associated with the **fear** and **anger** components

Question 45

What observation is the Gate theory of pain based on?

Answer 45

Based in part on the observation that other somatic input can alleviate pain (rubbing the area)

Question 46

What are the 3 steps involved in the Gate Theory of Pain (i.e., fibers, synapses, and NT's involved); what is the end result?

Answer 46

1) **Activate an Aβ fiber** by the normal stimuli. The Aβ fiber has a branch that travels via the dorsal columns, **but** it also branches within the SC 2) The Aβ fiber **releases EAA** and activates an **inhibitory interneuron** in the SC 3) The inhibitory interneuron releases **glycine** to **inhibit** the activity of the **second order neuron** in the pain pathway \***End result =** rubbing the area of skin activated by the Aβ fiber will**reduce** the sensation of pain

Question 47

What are the 5 steps involved in the descending mechanism of modifying painful inputs?

Answer 47

1) Neurons in **PAG** activated by **opiates, EAA, and cannibinoids** 2) Descending projections from PAG neurons travel to the midline **Raphe nuclei** and **release enkephalins**, activate the raphe neurons 3) Axons from raphe neurons travel to SC and release **serotonin,** activating **inhibitory** interneurons, causing release of **opitates** 4) **Opiates** from interneuron **activate** **Mu receptors** on the presynaptic terminal of the C fiber 5) Produces pre-synaptic inhibition that **reduces** release of **S****ubstance P** from the nociceptor, reducing pain transmission

Question 48

What are 2 functions of the descending serotonergic and noradrenergic neurons in the pain pathway?

Answer 48

1. Activate local interneurons 2. Suppress spinothalamic projection neurons

Question 49

Deep pain is usually associated with what structures, characterization of the pain, what kind of fibers and associated with what muscular movement?

Answer 49

- Associated with **periosteum, ligaments** - Usually **dull, achy** - Few A delta fibers - **Many C fibers** - Associated with **muscle spasm**

Question 50

What is the typical cause of Muscle Pain, types of fibers present and characterization of pain?

Answer 50

- Usually **injury** or **ischemia** during contraction - Both Group III and IV fibers - Get both **fast** and **slow pain** associated with muscle

Question 51

What is the localization of visceral pain, type of receptors, and is often associated with what type of pain?

Answer 51

- **Poorly localized** - Few receptors (almost all Group IV - C fibers) - Receptors very sensitive to stretch (distention) - Associated with **referred pain**

Question 52

What is required for the brain to be able to localize pain and how is this related to referred pain?

Answer 52

- Brain requires some experience to localize pain, starting early in life, this "trains" the brain to localize pain - Visceral pain is not experienced enough in early development to adequately train the brain to localize it - Confounded with the fact that the nociceptors may converge on the same interneuron in the SC

Question 53

Where are the group Ia/Aα fibers found vs. group Ib/Aα fibers found?

Answer 53

**- Group Ia/A**α are part of **muscle spindles** **- Group Ib/A**α are part of **Golgi tendon organs**

Question 54

Where are the group II or Aβ fibers found?

Answer 54

Cutaneous mechanoreceptors

Question 55

Where are the group III or Aδ fibers found?

Answer 55

Higher threshold mechanoreceptors, cold thermoreceptors, fast pain

Question 56

Which fibers have the highest threshold and why is this important?

Answer 56

- Group IV or C fibers - These are the **unmyelinated** fibers that are part of **nociceptors (SLOW pain)** - High threshold so that you are not constantly in pain!

Question 57

What are the sensory fibers of group I, II, III, and IV?

Answer 57

**Group I**: Ia and Ib = Aα **Group II:** Aβ fibers **Group III:** Aδ fibers **Group IV:** C fibers