Lecture 19- Pain Flashcards
1
Q
What is pain?
A
- Pain is an unpleasant sensory or emotional experience associated with actual or potential tissue damage (or described in terms of such damage)
- emotional too, the emotions resulting from pain
2
Q
What is pain for?
A
- Protective mechanism
- Awareness of damage occurring or about to occur
- telling you where the damage is
3
Q
What are the aspects associated with pain?
A
- Sensory-discriminative aspects: location, intensity, duration of the pain
- Motivational-affective dimension: unpleasant feeling associated with pain, the emotional aspects.
- other parts of the body= sweating, heartbeat, can induce flight or fight response
- Pain has an urgency.
- Pain can be modulated by behavioral experiences.
- There are neural mechanisms that can modulate pain transmission and the emotional reaction to pain.
(soldiers with pain don’t feel it if expecting to go home)
4
Q
What is the perception of pain dependent upon?
(What do you have to feel pain?)
A
- Cellular damage (tearage)
- this stimulates the sensory receptor stimulation
- this leads to activation of ascending neural pathways
- this activates the sensory cortex arousal
- and this leads to conscious awareness of pain
5
Q
What are the primary afferents?
A
- Sensory nerve terminals activated by tissue damage or by potentially damaging stimuli are called nociceptors
- unspecialized nerve endings, mostly located in epidermis
- can’t define them by endings, so they are defined by the conduction velocity of the axon fibres
6
Q
What are the two types of nociceptors? (based on velocity of conduction)
A
- Nociceptor axons are divided into two groups based on the properties of their axons.
1. Adelta-fibre axons - thinly myelinated with conduction velocities between 5-30 m/s
2. C-fibre axons - unmyelinated with conduction velocities <2 m/s, slowly conductive
7
Q
How else are nociceptors also classified? (by modality)
A
- Nociceptors are also classified by their modality (i.e. the sensory stimulus that activates them)
1. Mechanical nociceptors (Adelta-fibres): stimulated by cutting, crushing
2. Thermal nociceptors (Adelta- and C-fibres): respond to high temperature, noxious temperature is typically above 42 degrees centigrade, also low temperature
3. Polymodal nociceptors (C-fibres): all kinds of damaging stimuli, respond to wide range of stimuli, respon to chemicals, respond to more than one modality - These are high threshold receptors (i.e. they are normally activated by stimuli that produce damage or that have the potential to produce damage)
8
Q
How are the nociceptors activated?
A
These are high threshold receptors (i.e. they are normally activated by stimuli that produce damage or that have the potential to produced damage)
9
Q
What are the two types of pain perception elicited by activating nociceptors?
A
- Fast pain - a localized sensation of sharp, acute, pricking, stabbing pain felt immediately after a noxious stimulus is delivered. It usually disappears when the stimulus ceases (activation of Adelta-fibres).
- Slow pain - a diffuse aching, throbbing or burning pain (activation of C-fibres), more aversive pain, pain in muscle for example, dull and persistant, much worse that the fast, as you can’t dom muhc about it as easily
10
Q
How does the sensory nerve terminal work?
A
- it is a nerve ending
- there are channels (ion) that are involved in when the sensory stimulus is applied, the channels’ conductance changes in a way that leads to depolarization of the ending
- the depolarization spreads along the axon to where Na+ channels are (the very ending doesn’have to have Na+ channels)
- proximal to the nerve ending there are Na+ channels in quantities that you can elicit an action potential
- in a sense have two steps: inovlves activation od transduction channels that cause depolarization, that triggers the opening of Na+ channels that leads to further depolarization and to an action potential
- the step where action potential is produced is where the sensory information is encoded, the intensity of the stimulus is related to the frequency of the APs sent to the CNS
- there is info in the frequency with which the APs are sent to the CNS
- the step with initiating AP encodes some value of teh stimulus
- the channels are non selective cation channels, allow the movement of cations down their electrochemical gradient, in the case of Na+ channels: from outside to the inside, K+ from inside to outside
- when Na+ channels are open with membrane resting potential about -60mV, opening will lead to depolarization, this spreads then Na+ are activated and then AP an dthen is propagated
11
Q
What are the Thermo TRP channels?
A
- TRP transduction channels (there are several types, mechano, heat etc)
- TRP= transient receptor potential
- family of channels
- Thermo TRP channels are the ones that respond particularly to thermal stimulation but can also respond to chemical stimulation
- each type is activated by different temperature
- TRPV1= capsaican activates it (in chilli), ingredients in garlic and camphor, these are the channels that are activated when temp gets from below to above 42 degrees
- TRPV2= activated at higher temps
- TRPM8= temperatures in non noxious range, 28 degrees to below 10, these are the receptors that signal non noxious cooling, also involved in some noxious sensation, when very strongly activated can activate discomfort, strongly activated by mint (mint sweet= cooling, freshness)
- TRPA1= very cold temperatures, horseraddish, involved in cold pain, (the buring sensation of very cold), cinnamon too
12
Q
What is corneal recording good for and how is it done?
A
- record from the cornea
- front surface of the eye have nerves and terminate close to the cornea, almost out of the surface
- it is almost exclusively activated by nerves where when activated it causes discomfort (not a mix)
- densely innervated
- good as a study model
- apply suction electrode on the surface and record activity of the nerves
13
Q
What was the molecular identification of corneal sensory receptors? The experiment description
A
- recording from a type of receptor that responds to temperature when temp is decreasing, cooling is detected, not cold!
- the receptor continuously fires at constant temp, when heat= decrease in activity, and when cooling the frequency of firing increases
- called cold sensitive receptors, these receptors are thought to express the channel TRPM8 (the coooling and mint)
- can label the channel TRPM8 in the cornea
- only some nerve endings that respond to cold, most are polymodal
14
Q
What is sensitization?
A
- hyperalgesia/allodynia
- A change in neuronal sensitivity that results in heightened pain being generated by normally weakly painful or non-painful (innoxious) stimuli.
- e.g. -Sunburn - heightened sensitivity to thermal (warm) stimuli which normally doesn’t activate nociceptors
- Sore throat - swallowing becomes painful.
- allodynia is the bit where innoxious stimuli stimulate pain
- hyperalgesia where you get pain normally but the sensation is heightened
15
Q
What is peripheral sensitization?
A
A change in the “sensitivity” of nociceptors so that their threshold for activation is reduced. This change occurs in tissues that are inflamed.
16
Q
What is the nociceptor sensitization (acute)?
A
- Increase the sensitivity of the sensory transduction channels. = the endings are changed in their behaviour or a change in number of channels
or you can get
- Reduce the voltage threshold for activating voltage- activated Na+ channels (i.e. decrease the voltage threshold for initiating action potentials).=
17
Q
What is the peripheral sensitization-tissue inflammation?
A
- Activation of ‘peptidergic’ nociceptors contributes to the inflammatory response (neurogenic inflammation)
- A sub-population of C-fibre nociceptors contain and release calcitonin gene-related peptide (CGRP) and substance P
- APs spread to the CNS but also to collateral axons
- nociceptive fibres that release peptides have both afferent and efferent function
- action potential propagated to collateral axons
= this is called axon reflex!
- the peptidonergic neurons have two peptides they release: CGRP and substance P
- collateral axons can innervate blood vessels, the release of CGRP(calcitonin gene related peptide) produces vasodialation= the skin reddens
- substance P causes the venules to become leaky= leak fluid into the tissue
- other collateral axons innervate mast cells, substance P activates them= release histamine, and histamine contributes backs to the activation and can act on the blood vessel
=the process is neurogenic inflammation! the neurons inflame the tissue, get local inflammation response, then skin thickens= edema= leakage of fluid from blood vessels
-positive feedback= the nerve activation increases it by substance P release
19
Q
What are the receptors at play in acute peripheral sensitization?
A
-Phosphorylation of TRPV1 channels makes them more sensitive to thermal stimuli -Phosphorylation of Na+ channels make them more readily activated (reducing the threshold for activating action potentials)
22
Q
What are prostaglandins?
A
- COX-2 - the inducible isoform of cyclo-oxygenase
- Non-steroid anti-inflammatory drugs (NSAIDs; e.g. Asprin, Ibuprofen) inhibit COX-2.= that is why it doesn’t hurt, the analgesic properties of the drugs, they block the formation of prostaglandins
- important agents that induce sensitiation of nociceptors
- they are formed by the drug COX2 acting on the archadonic acid
25
Q
How does acute peripheral sensitization work?
A
- Phosphorylation of TRPV1 channels makes them more sensitive to thermal stimuli
- Phosphorylation of Na+ channels make them more readily activated (reducing the threshold for activating action potentials
- the kinases phosphorylate, act at the transduction channels (the TRPV1 for example) and also at the Na+ channels
