Touch, Pain, Itch: Module 3.3 - 3.5 Flashcards
What are the two types of touch?
- Active Touch
- Passive touch
What is active touch?
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
What is Passive Touch
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.
How many receptors provide touch sensation in the human hand?
4
Touch is a combined result of all of them.
What are the two types of axons tha innervate the 4 mechanoreceptors of the hand?
- SA (Slow Adapting)- Respond to steady skin indentation with a sustained discharge.
- RA (Rapid Adapting) - Fibers stop firing when indentation becomes stationary.
What are the 4 types of mechanoreceptors of the hand?
What are the characteristics of the 4 Mechanoreceptors of the hand?
Explain the organization of receptors in glabrous skin.
What are receptive fields?
Limited area in which mechanoreceptros convey sensory information.
Explain the difference between the receptive fields of Type 1 and Type 2 fibers.
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.
What place on the hand has the keenest sensitivity?
The distal pad of the index finger.
How do they use receptive fields for braille reading?
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.
What do SA fibers actually sense and what properties of an object can this tell us?
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.
What specific deformation to SA2 fibers innervating Ruffini ending respond to?
Stretching of the Skin
What do RA fibers actually sense?
Sense Motion and Vibration.
Vibration sense is a useful measurement of dynamic sensitivity to touch.
What is the most sensitive mechano-receptor in the somatosensory system and best sensitive to vibratory simuli?
RA2 Pacinian Corpuscle
What is the best studied touch receptor organ?
Merkel Cell
Where do merkel cells usually cluster?
Cluster in swellings of hairy skins (touch domes).
Near the center of the fingerprint ridges in glabrous skin.
What are Markel cell-neutrie complexes?
Sensory epithelial cells innervated by large diameter AB sensory axons.
Explain signal transduction in regards to touch of Merkel Cells.
What are the two examples of merkel cell recordings?
What are the 2 Piezo protein isoforms?
- Piezo1: Found primarily in nonneural tissue, such as epithelia in blood vessels the kidneym and bladderm and in RBCs.
- 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.
Explain structural characteristics of the Piezo Protein family.
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
What conditions can arise from loss of Piezo 2?
What are the differences in activation between Piezo1 and Piezo2?
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.
What is pain?
- The ability ot detect noxious stimuli.
- Is essential to an organisms survival and wellbeing.
What are the 2 types of pain?
- Acute
- Chronic - Pathological
What are the 2 ways someone can have a change in pain perception?
- Reduced Sensitivity (Leads to injury) (Can involve other tissues)
- Increased sensitivity (Allodyna and hyperalgesia)
Reduced can lead to amputation in type 2 diabetes.
What is nociception?
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.
What are nociceptors and what are the 3 types?
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
These three classes of nociceptors are widely distributed in skin and deep
tissues and are often co-activated.
How are the different type of nerve fibers are involved with pain and nociceptive transmission?
No Pain (Myelinated)
Aa Fibers: Proprioception
AB Fibers: Touch
Pain
Ad Fibers: Pain and Temp
C Fibers: Pain, Temp and Itch (Not Myelinated)
Explain the different regions of the dorsal horn and what they recieve.
What are the 4 Ascending Nociceptive Pathways?
- Spinothalamic
- Spinoreticular Tracct
- Spinoparabrachial Tract
- Spinohypothalamic Tract
Explain the Gate control theory of pain.
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.
What is referred pain?
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.
What is a possible explanation for referred pain?
The convergence of somatic and visceral nociceptive inputs onto lamina V neruons.
What are two common changes in pain perception?
- Allodynia
- Hyperalgesia
What is Allodynia?
Pain in respoinse to stimuli that aare normally innocuous (not harmful).
Light storking sunburnt skin, movement of joints with arthritis.
Whatis hyperalgesia?
An exaggerated response to noxious stimuli.
Persistent pain in absence of sensory stimulation.
What are 2 types of chronic pain?
- Nociceptive pain
- Neuropathic Pain
What causes Nociceptive Pain?
Activation of nociceptors in the skin or soft tissue in response to tissue injury. Occurs with inflammation.
Treated with NSAIDS or opiates.
What causes Neuropathic Pain?
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.
What is the primary NT released by Nociceptors and what are the cotransmitters released?
Primary: Glutamate
Cotransmitters: Neuropeptides - Substance P, CGRP, somatostatin, galanin.
Glutamate stored in small vesicles, NPeptides stored in dense core ones.
Explain sensitization of peripheral nociceptors.
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.
What is the main molecule contributing to sensitization?
Bradykinin (Active Pain-producing agent) - Activates Ad and C nociceptors.
Decreaes firing threshold.
Explain How Neurogenic inflammation works.
What is the mechanism in which Bradykinin works to increase sensitivity?
Modulates TRP Channels
Amplifies Heat TRP and inhibits Cold TRP.
What is a major contributor to neuropathic pain due to nerve injury?
Central Sensitization
Can Decrease pain thesholds leading to allodynia and spontaneous pain.
How does central sensitization work?
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
What is analgesia?
Insensibility to pain without loss of consciousness.
What are some examples of opiod receptors?
Mu, Delta, Kappa, Orphanin
What are some endogenous opioids?
Enkephalins, B-Endorphins, Dynorphins
Why is morphine use as an analgesic?
Morphine controls pain by activating opioid receptors and by mimicking the actions of endogenous opioid peptides.
What are the 2 effects of opiodids on nociceptor signal transmission?
- Presynaptic (DRG) - Reducing Ca entry and NT release.
- Postsynaptic (projection neuron) - Increase K conductance, hyperpolariztion and increasing activation threshold (hyposensitivity).
What is the mechanism in which opioids work?
What is an itch and what it its purpose?
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.
What are 2 related sensations, what type of neurons are they detected by, what are there behavioral respones?
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.
Can pain supress itch?
Yes
Pain generated by scratching relieves itchy sensation.
Can Itch Suppress Pain?
Rarely
Can Itch Responsive Neurons in the DRG and Spinal Cord be activated by Pain?
Yes
What is the inensity theory?
Poly-modal sensory neurons respond to both pain and itch stimuli.
Strong stimuli generate pain where weaker generate itch.
However… weaker painful stimuli or stronger itchy
stimuli fail to turn into a different sensation, thus
raising questions about the intensity theory.
What is the selectivity theory?
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
What places is itch confined to?
Skin, Ocular Conjuctiva, Mucosa
What are itch specific peripheral sensory neurons called?
Pruiceptors
Sub group of nociceptive neurons.
What discovery led itch to be a seperate biological and sensory process from pain?
The discovery of an itch-specific pathwag in the NS defined by gastrin-releasing peptide and its receptors.
What axon types is involved in Nociception and Pruriception?
Ad and C fibers.
What ascending pathway does itch take?
Same Pathway through the Spinothalamic Tract
What is acute itch and what is its mechanism?
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)
What can chronic itch be caused by and what is the mechanism throught to be?
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
What is chronic itch frequently accompanied by?
Allokinesis and HyperKinesis
Involuntary Motion
What are the 3 Pruriceptor classification and what are they activated by?
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)
Explain the NP3 - Mediated Itch Pathway.
What is the mechanism of histamine-dependant (Acute) itch?
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
What is the mechanism of histamine-independent (chronic) itch?
What do TRPA1 receptors bind?
Bind pungent substances such as horeseradish, garlic, onions, allium expressing plants.
Produce pain or itch due to covalent modification of cysteines in TRPA1
What are the 2 types of itch-selective nerves and what are the different receptors expressed on them.
- Histaminergic - H1R and H4R Receptor
- Nonhistaminergic - Variety of receptors responding to other pruritogens.
How can TRPa1 receptors mediate itch when they are also involved in sensing noxious cold temeratures?
Noxius cold is sensed when both TRPA1 and TRPM8 receptors are excited, but itch is perceived when TRPM8 receptors are silent/not present.
Why do some TRPV1-expressing fibers mediate itch sensations rather than sensations of noxious heat?
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)
