Touch, Pain, Itch: Module 3.3 - 3.5

Question 1

What are the two types of touch?

Answer 1

1. Active Touch
2. Passive touch

Question 2

What is active touch?

Answer 2

Top Down Process - You Initiate; CNS already recognizes and is aware of the same feeling; brain first.

During active touch, somatosenesory information depicts the physical properties of objects as well as the motor action sof the hand and arm, and their relation to task goals.

You move your hand

Question 3

What is Passive Touch

Answer 3

Bottom Up Process - No preperation.

During passive touch, the subject reacts to external stimuli specifid bu the experimeter, clinican, someone else. The stimulus iscontrolled bu the someone else, and the subject needs to analyze all of the transmitted somatosensory information and select specific features part by the task instructions.

Question 4

How many receptors provide touch sensation in the human hand?

Answer 4

4

Touch is a combined result of all of them.

Question 5

What are the two types of axons tha innervate the 4 mechanoreceptors of the hand?

Answer 5

1. SA (Slow Adapting)- Respond to steady skin indentation with a sustained discharge.
2. RA (Rapid Adapting) - Fibers stop firing when indentation becomes stationary.

Question 6

What are the 4 types of mechanoreceptors of the hand?

Answer 6

Meissner and Merkl - Have the most innervation and close to top of the skin. Charts: RA, SA, RA, SA

Question 7

What are the characteristics of the 4 Mechanoreceptors of the hand?

Answer 7

Pay attention to Types, Best Stimulus, Response to Sustained Indentation.

Question 8

Explain the organization of receptors in glabrous skin.

Answer 8

Receptors are innerated by large-diameter AB myelinated fibers. Fibers branch at their terminals to innervate several receptor organs. For Pacinian and Ruffini Corpuscles, fibers innervate only one receptor organ.

Question 9

What are receptive fields?

Answer 9

Limited area in which mechanoreceptros convey sensory information.

Question 10

Explain the difference between the receptive fields of Type 1 and Type 2 fibers.

Answer 10

Type 1 fibers have small, highly localized receptive fields withmultiple spots of high sensitivity that reflect the branching patterns of their axon terminals in the skin. An RA1 axon typically innervates 10-20 Meissner corpuscles, while an SA1fiber innervates approximately 20 Merkel cells.

Type 2 fibers innervating the deep layers of skin are connected to only a single Pacinian corpuscle or Ruffini ending. As these receptors are large, they collect information from a broader area of skin. Their receptive fields typically contain a single “hot spot” where sensitivity to touch is
greatest; this point is located directly above the receptor.

Question 11

What place on the hand has the keenest sensitivity?

Answer 11

The distal pad of the index finger.

Question 12

How do they use receptive fields for braille reading?

Answer 12

Dots spaced 3 mm apart, which is farther apart than the receptive field diameter of an SA1(Merkel) Fiber.

Also use RA1 however SA1 is the most.

Fires a burst when dot is in the field and is silent when dot leaves.

Question 13

What do SA fibers actually sense and what properties of an object can this tell us?

Answer 13

SA1 and SA2 signal skin deformation and pressure.

Sensitive to edges, corners, points, and curvature, compliance, shape, size, surface texture.

We percieve an object as hard if it indents the skin and soft if we deform the object.

Question 14

What specific deformation to SA2 fibers innervating Ruffini ending respond to?

Answer 14

Stretching of the Skin

Question 15

What do RA fibers actually sense?

Answer 15

Sense Motion and Vibration.

Vibration sense is a useful measurement of dynamic sensitivity to touch.

Question 16

What is the most sensitive mechano-receptor in the somatosensory system and best sensitive to vibratory simuli?

Answer 16

RA2 Pacinian Corpuscle

Can activate SA1 and RA1 but weaker. RA2 responsive to high freq 30-500hz vibrtions.

Question 17

What is the best studied touch receptor organ?

Answer 17

Merkel Cell

Question 18

Where do merkel cells usually cluster?

Answer 18

Cluster in swellings of hairy skins (touch domes).

Near the center of the fingerprint ridges in glabrous skin.

Question 19

What are Markel cell-neutrie complexes?

Answer 19

Sensory epithelial cells innervated by large diameter AB sensory axons.

Question 20

Explain signal transduction in regards to touch of Merkel Cells.

Answer 20

Touch triggers a train of action potentials (frequency proportional to the velocity and amplitude of stimulus) Piezo2 is expressed in both, Merkel cell and the SA1. Diagram-Sensory Transduction: Piezo2 channels in sensory neuron open uponstimulation (1) generating the initial dynamic response to touch (2). Skin deformation simultaneously activates Piezo2 channels in the Merkel cell (3), depolarizing activates Cav (4), and release neurotransmitter continuously (5). Binding of the neurotransmitter further depolarizes the SA1 neurite, producing sustain

Question 21

What are the two examples of merkel cell recordings?

Answer 21

Piezo 2 Receptor Current goes through 0 because it is Cation Non-Selective

Question 22

What are the 2 Piezo protein isoforms?

Answer 22

1. Piezo1: Found primarily in nonneural tissue, such as epithelia in blood vessels the kidneym and bladderm and in RBCs.
2. Piezo2: Expressed in Mechanosensory DRG and tregeminal neurons tha tmediate the senses of touch and proprioception and in vagal afferents innervating smooth muscle of the lung, where they sense lung stretch.

Question 23

Explain structural characteristics of the Piezo Protein family.

Answer 23

The Piezo protein family of transmembrane ion channels are molecular mediators of mechanoreception in mammals.

Piezo1 proteins are composed of approximately 2,500 amino acids, with at least 26 transmembrane α-helices.

The ion channel is a** trimer formed from three identical subunits**, with two pore-forming α-helices at the C-terminal end of each Piezo protein.

The N-terminals of the subunits form a propeller-like structure, which is thought to be involved in coupling mechanical stimuli to channelgating.

They form cation non-selective channels

Question 24

What conditions can arise from loss of Piezo 2?

Answer 24

Question 25

What are the differences in activation between Piezo1 and Piezo2?

Answer 25

**Piezo1**: Activated by both negative and postiive pressure. - Due to being in Gut in which pressure can go both ways. **Piezo 2**: Activated by only postive pressure. - Most important in Proprioception.

Question 26

What is pain?

Answer 26

* The ability ot detect noxious stimuli. * Is essential to an organisms survival and wellbeing.

Question 27

What are the 2 types of pain?

Answer 27

* Acute * Chronic - Pathological

Question 28

What are the 2 ways someone can have a change in pain perception?

Answer 28

* **Reduced Sensitivity** (Leads to injury) (Can involve other tissues) * **Increased sensitivity** (Allodyna and hyperalgesia) | Reduced can lead to amputation in type 2 diabetes.

Question 29

What is nociception?

Answer 29

The process by which intense thermal, mechanical, or chemical stimuli are detected by a subpopulation of peripheral nerve fibers, called nociceptors. | Refers to whole structures not specific receptors.

Question 30

What are nociceptors and what are the 3 types?

Answer 30

**Nociceptors:** Free nerve endings of primary sensory neurons. ** 3 Types:** 1) **Thermal nociceptors:** activated by temp. > 45°C or < than 5°C. They include myelinated Aδ fibers (5-30 m/s) and unmyelinated C-fibers (1 m/s). 2) **Mechanical nociceptors**: activated by intense pressure applied to the skin. Also endings of myelinated Aδ axons. 3) **Polymodal nociceptors:** activated by high-intensity mechanical, chemical, or thermal (both hot and cold) stimuli. Predominantly of unmyelinated C fibers ## Footnote These three classes of nociceptors are widely distributed in skin and deep tissues and are often co-activated.

Question 31

How are the different type of nerve fibers are involved with pain and nociceptive transmission?

Answer 31

**No Pain** (Myelinated) Aa Fibers: Proprioception AB Fibers: Touch **Pain** Ad Fibers: Pain and Temp C Fibers: Pain, Temp and Itch (Not Myelinated)

Question 32

Explain the different regions of the dorsal horn and what they recieve.

Answer 32

Question 33

What are the 4 Ascending Nociceptive Pathways?

Answer 33

1. Spinothalamic 2. Spinoreticular Tracct 3. Spinoparabrachial Tract 4. Spinohypothalamic Tract

Question 34

Explain the Gate control theory of pain.

Answer 34

Theory states that the spinal cord has a gating mechanism that controls whether pain signals are sent to the brain or not. Possible reason why rubbing the site of pain can alleviate the pain.

Question 35

What is referred pain?

Answer 35

Is a condition in which pain from injury to a visceral tissue is percieved as originating from a region of the body surface. Associated with large organs -> Possible adaptive advantage targeting extremeties to cause rest when internal organs are in pain.

Question 36

What is a possible explanation for referred pain?

Answer 36

The convergence of somatic and visceral nociceptive inputs onto lamina V neruons.

Question 37

What are two common changes in pain perception?

Answer 37

* Allodynia * Hyperalgesia

Question 38

What is Allodynia?

Answer 38

Pain in respoinse to stimuli that aare normally innocuous (not harmful). | Light storking sunburnt skin, movement of joints with arthritis.

Question 39

Whatis hyperalgesia?

Answer 39

An exaggerated response to noxious stimuli. | Persistent pain in absence of sensory stimulation.

Question 40

What are 2 types of chronic pain?

Answer 40

1. Nociceptive pain 2. Neuropathic Pain

Question 41

What causes Nociceptive Pain?

Answer 41

Activation of nociceptors in the skin or soft tissue in response to tissue injury. Occurs with inflammation. | Treated with NSAIDS or opiates.

Question 42

What causes Neuropathic Pain?

Answer 42

Results from **direct injury to nerves** in the PNS or CNS. Burning or Electric Sensation. (egL shingles, phantom limb pain) | Responds to NSAIDS not opiates.

Question 43

What is the primary NT released by Nociceptors and what are the cotransmitters released?

Answer 43

**Primary:** Glutamate **Cotransmitters:** Neuropeptides - Substance P, CGRP, somatostatin, galanin. | Glutamate stored in small vesicles, NPeptides stored in dense core ones.

Question 44

Explain sensitization of peripheral nociceptors.

Answer 44

Damaged tissues release a cocktail of peptides and proteins. This cocktail decreases the threshold of nociceptor activation. Local - Red area around injury is sensitized. | Bradykinin, Substance P, Nerve Growth Factor, ATP, Histamine, 5HT, etc.

Question 45

What is the main molecule contributing to sensitization?

Answer 45

**Bradykinin** (Active Pain-producing agent) - Activates Ad and C nociceptors. | Decreaes firing threshold.

Question 46

Explain How Neurogenic inflammation works.

Answer 46

Question 47

What is the mechanism in which Bradykinin works to increase sensitivity?

Answer 47

Modulates TRP Channels Amplifies Heat TRP and inhibits Cold TRP.

Question 48

What is a major contributor to neuropathic pain due to nerve injury?

Answer 48

Central Sensitization | Can Decrease pain thesholds leading to allodynia and spontaneous pain.

Question 49

How does central sensitization work?

Answer 49

**Repeated Exposure to noxious stimuli results in long term changes in the dorsal horn neurons**. Prolonged changes in dorsal horn neurons constitute a "memory" of C fiber input. | Involves C fibers, NMDA receptors, and need Neuropeptides

Question 50

What is analgesia?

Answer 50

Insensibility to pain without loss of consciousness.

Question 51

What are some examples of opiod receptors?

Answer 51

Mu, Delta, Kappa, Orphanin

Question 52

What are some endogenous opioids?

Answer 52

Enkephalins, B-Endorphins, Dynorphins

Question 53

Why is morphine use as an analgesic?

Answer 53

Morphine controls pain by **activating opioid receptors** and by **mimicking** the actions of **endogenous opioid peptides**.

Question 54

What are the 2 effects of opiodids on nociceptor signal transmission?

Answer 54

* **Presynaptic (DRG)** - Reducing Ca entry and NT release. * **Postsynaptic (projection neuron)** - Increase K conductance, hyperpolariztion and increasing activation threshold (hyposensitivity).

Question 55

What is the mechanism in which opioids work?

Answer 55

Question 56

What is an itch and what it its purpose?

Answer 56

Acute Pruitus (itch) serves as an alarm signal to protect the body against potentially harmful environamental threats (parasites, noxious plants or other irritants. **The scratch reponse helps to remove these irritants from the skin and reduces the itch sensation.**

Question 57

What are 2 related sensations, what type of neurons are they detected by, what are there behavioral respones?

Answer 57

**Pain and Itch** **Detected:** By small diamter DRG Neurons. **2 Behavioral Responses** Itch - Elicits scratching to remove irritants Pain - Generates a withdrawal response to avoid tissue damage.

Question 58

Can pain supress itch?

Answer 58

Yes | Pain generated by scratching relieves itchy sensation.

Question 59

Can Itch Suppress Pain?

Answer 59

Rarely

Question 60

Can Itch Responsive Neurons in the DRG and Spinal Cord be activated by Pain?

Answer 60

Yes

Question 61

What is the inensity theory?

Answer 61

Poly-modal sensory neurons respond to both pain and itch stimuli. **Strong stimuli generate pain where weaker generate itch.** ## Footnote However... weaker painful stimuli or stronger itchy stimuli fail to turn into a different sensation, thus raising questions about the intensity theory.

Question 62

What is the selectivity theory?

Answer 62

**Itchy stimuli specifically activate itch selective neurons** to generate itch sensation. **Painful stimuli activate both itch and a larger nociceptive population** whose activation inhibits itch to produce only pain sensation

Question 63

What places is itch confined to?

Answer 63

Skin, Ocular Conjuctiva, Mucosa

Question 64

What are itch specific peripheral sensory neurons called?

Answer 64

Pruiceptors | Sub group of nociceptive neurons.

Question 65

What discovery led itch to be a seperate biological and sensory process from pain?

Answer 65

The discovery of an itch-specific pathwag in the NS defined by **gastrin-releasing peptide** and its receptors.

Question 66

What axon types is involved in Nociception and Pruriception?

Answer 66

Ad and C fibers.

Question 67

What ascending pathway does itch take?

Answer 67

Same Pathway through the Spinothalamic Tract

Question 68

What is acute itch and what is its mechanism?

Answer 68

**Acute pruritus (itch) serves as an alarm signal to protect the body against potentially harmful environmental threats.** Mainly **mediated by histamine-responsive sensory neurons** in the skin that are relatively insensitive to mechanical pain stimuli but also respond to noxious chemicals such as capsaicin (TRPV1 agonist)

Question 69

What can chronic itch be caused by and what is the mechanism throught to be?

Answer 69

Seriously debilitating symptom accompanying various cutaneous and systemic disorders but may also be caused by drugs such as the anti-malaria drug chloroquine. Antihistamines do not improve some chronic itching, suggesting that it is **mediated via histamine- independent pathways**

Question 70

What is chronic itch frequently accompanied by?

Answer 70

Allokinesis and HyperKinesis | Involuntary Motion

Question 71

What are the 3 Pruriceptor classification and what are they activated by?

Answer 71

**NP1:** *Activated specifically by β-alanine*. NP1 expresses the B-alanine receptor MrgprD **NP2:** *Activated by chloroquine*. NP2 expresses its receptor MrgprA3 **NP3:** Defined in part by its expression of the receptor for IL-31 (IL-31RA)

Question 72

Explain the NP3 - Mediated Itch Pathway.

Answer 72

Question 73

What is the mechanism of histamine-dependant (Acute) itch?

Answer 73

Itch induced by intradermal injection of histamine or by procedures that release endogenous histamine **activates a subset of TRPV1-expressing neurons that also contain the H1 histamine receptor;** these itch sensations are blocked by antihistamines. **It requires phosphorylation of TRPV1 (PKC**

Question 74

What is the mechanism of histamine-independent (chronic) itch?

Answer 74

Question 75

What do TRPA1 receptors bind?

Answer 75

Bind pungent substances such as horeseradish, garlic, onions, allium expressing plants. | Produce pain or itch due to covalent modification of cysteines in TRPA1

Question 76

What are the 2 types of itch-selective nerves and what are the different receptors expressed on them.

Answer 76

1. **Histaminergic** - H1R and H4R Receptor 2. **Nonhistaminergic** - Variety of receptors responding to other pruritogens.

Question 77

How can TRPa1 receptors mediate itch when they are also involved in sensing noxious cold temeratures?

Answer 77

**Noxius cold is sensed when both TRPA1 and TRPM8 receptors are excited**, but **itch** is perceived when **TRPM8 receptors are silent/not present**.

Question 78

Why do some TRPV1-expressing fibers mediate itch sensations rather than sensations of noxious heat?

Answer 78

**Heat pain is sensed when TRPV1-, TRPV2-, and TRPV3-expressing fibers are co-activated**, but **itch** may be **perceived when only TRPV1**- expressing fibers respond and TRPV2 and TRPV3 receptors are silent (or not present)