Block C - Pain Flashcards
How does pain differ from nociception?
Pain is mulidimensional and refers to a unique sensory and emotional response to pain. Whereas, nocieption is the neural process which encodes for noxious stimuli
What are 4 main benefits of pain and what would happen if she didn’t have pain mechanisms?
- withdrawal reflex
- Tissue repair and healing
- Pain learning
- motivates seeking treatment
If we didnt have pain then indiviudals will be greatly impacted by injury, infection ,self mutaliation and in some cases succumb to early death
True or False: All pain has a function.
False, there are some pain types that have no function at all
what are the main dimensions of pain?
- Intensity - pain scale, mild, moderate and severe
- characteristics - is it sharp, dull, aching
- Modality - heat, physical touch
- Location - superficial or deep, focal or diffuse
- Time - acute or chronic
- Behaviour - how is the pain effecting behavioural response
- Emotion
What is the 3 broad classification of pain
- nociceptive
- inflammatory
- pathological
What is nociceptive pain, what are the subtypes?
Nociceptive pain is physical or potential damage to body tissue in response to basic modality like temperature and mechanical pressure.
The 3 subtypes include:
1. Superficial somatic
2. Deep somatic
3. Visceral pain
For each nociceptive pain type, name effected tissue, stimuli, characteristics and localisation
Superficial somatic:
tissue - skin and superficial tissues
Stimuli - burns, abrasions, lacerations
Character: Sharp burning pain
Localisation: Easy to locate and well define
Deep somatic:
Tissue - bones, tendons, ligaments
Stimuli - sprains, strains and fractures
character: dull aching pain
localisation: Difficult to locate
Visceral pain:
Tissue - internal organs
stimuli - hypoxia, inflammation, ischemica, stretching
character: dull deep squeezing pain, hard to explain
localisation - diffuse and hard to localise as in most cases pain will be felt distant to the origin site
What is the basic pathway for pain peception
- noxious stimulus
- detection by nociceptors
- tranduction via nociceptive neurons to CNS
- activation of motor pathway at level of spinal cord - for reflex if required
- modulation occurring at spinal level
- Perception - high order brain regions which facilitate multidimensional aspect of pain
What is inflammatory pain and what are the 2 subtypes asscociated with this kind of pain
Pain that is associated with tissue injury and peripheral inflammation which often results in pain hypersenitivity
2 types:
Hyperalgesia: Increase pain sensitivity to a stimulus that usually evokes pain
allodynia: increased pain sensitivity to a stimulus which doesn’t usally evoke pain
True or False: Inflammatory pain is associated with protection and repair. Justify answer.
True, inflammatory pain increase pain sensitivity which prevents an individual from interaction with pain stimulus which has the ability to worsen original injury.
What is pathological pain and what the subtypes?
Pathological pain is similar to nocieceptive and inflammatory pain but also carries neuroimmune componants. 3 types include, phatom pain (pain in amputed limbs where nerves have been severed), neuropathic pain (pain from damaged peripheral nerves and not directly from injury site) and psychogenic pain (emotions, mental state and behaviour)
Compare the threshold type and adaptiveness of each pain type
Nociceptive pain
- adaptive
- high threshold
inflammatory pain
- adaptive
-Low threshold
Pathological pain
- maladaptive
- low threshold
Name the 3 main nociceptive stimuli
- Thermal
- chemical
- Mechanical
Name 5 types of nocicpetors
- Mechanoreceptors
- chemical receptors
- mechano-thermoceptors
- polymodel: can detect all 3 stimuli
- slient - low threshold, only activated when injury is present
SP and CGPR are commonly released from nociceptive fibres. How do they influence pain sensation?
These peptide will play a role in histamine release, vasodialation and brady kinin release which will extend, broaden and amplify pain so that it can be felt beyound the site of injury
Explain chemical mediators and how they influence hyperalgesia and allodynia.
Damage cells at the injury site will release prostagladins, bradykinin and sertonin which then act on specific receptor to sensitise (hyperalgesia) and activate silent receptors (allodynia)
What are the 2 types of afferent fibres for nociception and compare and contrast they characteristics
A delta and C fibres which are both thin fibres that release glutamate. A delta fibres are myelinated and so there conduction velocity is higher than C fibres. A delta fibres play a role in superfical somatic pain so that very sharp, immediate pricking pain. These fibres have small receptive field which allows for pain to be easily localised. C fibres however, are unmyelinated and this have a slower conduction velocity. Alongwith glutamate, c fbres will also release SP and thus have a sustained response. These fibres are associated with deep somatic and viseral pain and is rather hard to localise due to larger receptors fields.
both fibres will terminate in the dorsal horn by synapsing with 2 order nociceptive dorsal horn neurons
what are the two main excitatory NT’s and what do they target
Glutamate which targets AMPA receptors
SP which targets NK1 receptor
describe the withdrawal arc and how nociceptive connections facilate this.
nocieptive fibre so a delta and c fibre are poly synaptic and so not sonly do they synpase with upper control centres but they also synapse with one inhibitory interneuron and one excitatory neuron. These intern neurons then synapse with afferent motor neurons. So in withdrawl arc reflex. one inhibitory interneuron will inhibit the anatgonist muscle and they other will excite the agonist muscle.
What are the 3 spinothalamic tracts of ascending pain pathway and are they specific or not specific?
- Neospinothalamic - synpase only with pain specific neurons
- paleospinothalamic - synapses with either non-specific neuron and pain specific neurons
- arcispinothalamic ^
What fibres correspond with each spinothalamic tract?
Neospinothalamic - Adelta fibres
Archispinal and paleospinal thalamic - C fibres
Match each spinothalamic tract with type of nociceptive pain type
Superficial somatic - Neo, Paleo and Archispinal
Deep somatic - Paleo and archispinal
Vicersal - Paleo and Archispinal
Breifly describe the pathway for Neospinal and paleo,archispinal tracts
Neospinal: A delta –> VPM –> primary somatosensory cotex
Paleo,Archispinal: C fibres –> IL –> secondary somatosensory cortex
What is referred pain? Provide an example.
Referred pain is when a superficial somatic and viseceral primary afferent converge on the same 2nd order neuron in paleospinal thalamic tract and so there is perception of pain at the superficial site die to focal and small receptive fields rather than the organ.
An example of this is a myocardial infraction where by pain is felt in the arm rather than the heart
Name 5 brain regions and there associated role in pain
- Primary somatosensory cortex - perception of pain
- Secondary somatosensory cortex - recognising and remembering pain
- PAG - descending modulatolry control
- Reticular formation and hypothalamus - autonomic control
- Insular, cingulate & frontal cortices - emotional aspect
What is the gate control theory?
Non painful inputs can close the gate to painful inputs to CNS. Non nociceptive neurons and nociceptive neurons project to inhibitory interneuron. Nocicpetive fibres will inhibit the interneuron while non nocicpetive neurons will excite. the relative frequencies of AP from nocicpetive and non-nocicpetive neurons will determine how open the gate is and how much pain information is passing through
name the 2 excitatory transmitters and 2 inhibitory transmitter/receptors in pain modulation? State whether they are found post/presynaptically.
Excitatory:
Glutamate presynaptically to bind on AMPA post synaptically
SP presynaptically to bind to NK1R postsynaptically
Inhibitory:
Opioid receptors that sit on post synaptic neuron
Gabageric neurons from PAG will release GABA which then bind post synaptically
Descending sertonergic neurons which interaction with postsynaptic neurons will release serotonin which binds to 5HT receptors in post synaptic neuron
Whats the different between analgesic and anaesthetic
analgesics act to relieve pain without loss of consciousness while anaesthetics act to inhibit response to stimulus with (general) or without (local) loss of consciousness and loss of vital functions
How do NSAIDs work?
Inhibits prostagladin synthesis by inhibiting COX enzyme. Has main role in periphery but can also work at conduction and modulation level
How does opioids work?
Act on as agonists on opiodergic receptors which causes block of NT release (via preventing influx of Ca). Opiods work primarily on the conduction pathway and perception in cortex
Can also effect GABAgeric neurons in PAG by dishibiting them and therefore allowing excitation of PAG neurons to release serotonin
Step out the levels of pain perception with the local of each level
Transduction in the periphery
Conduction in the dorsal horn of the spinal cord
Modulation in the desending pathways
Transmission at the thalamus
Perception in the cortex
How does local anaesthesia work?
Works by inhibtiong sodium voltage gated channel therefore preventing APs from arise
Compare the difference between reflexive tests and non-reflexive tests
Reflexive test look at periphery and spinal cord by assessing automatic responses from pain. Whereas, non reflexive looks at higher cortical perception, desending modulation and clinical assessments of pain through behaviour responses
For animal models, name 3 reflexive tests for thermal pain
- Tail flick - apply heat onto tail and observe how often they flick tail
- Hot plate - place animal on hot plate and observe how often they lift or lick there paw - this looks at both automatic responses but also behavioural response (paw licking is higher order)
- Hargreaves - similar to hot plate but heat is only apply to hind legs for example - this allows for there to be a control and effected
For animal models, name 2 reflexive tests for mechanical pain
- Vonfrey - test an assortment of filaments with different flexibility/pressure but applying them to paw of animal and observe when they lift there foot - thus look at superficial pain
- applying mechanical pressure to a muscle, joint or paw to assess deep somatic pain
what kind of pain does von frey filaments look at
mechincal allodynia in neuropathic and inflmmatory pain
What are the 2 principals you must consider when selecting an appropriate pain model
- understand clinical presentation of pathology known as face validity - use this to match pathology with kind of test for example post surgical pain pathology would match with a post surgical pain model
- behavioural measures that assess issues of that particular disease
What does a acute post surgical pain model look like?
often involves incision of superficial and deep tissue then sutured up. Vonfrey filaments are then place adjacent to surgery site to assess mechanical allodynia following surgery. Another aspect this pain model looks at is guarding behaviour and how the animal guards the incision site.
Briefly describe what a inflammatory pain model looks like.
Injection of irritants in skin, paw, muscle, joint or organ to replicate inflammatory disorders.
Compare the chemicals which are used for an acute and chronic inflammatory pain model
For acute inflammatory pain capsaicin is injection and binding of this chemical with the TRPV1 receptor will cause local neurogenic inflammation, thermal and mechanical hyperalgesia and mechanical allodynia in surround around. Carrageen is another chemical which generate both acute and chronic inflammatory pain. This chemical replicates inflammatory pain seen in sprains, strains and myositis. Another way to assess chronic inflammatory pain is freund adjvant which generates hyperalgesia + behavioural and functional responses seen in inflammatory disorders
Generally neuropathic pain is difficult to assess. In animal models, how is neuropathic pain replicated?
If looking at spinal cord then that usually involves surgically lesioning the cord, laser injury or contusion however, if looking at peripheral nerve injury then you can tie, transect and lesion nerves
Another model of neuropathic pain is chronic constriction injury which works by contricting the sciatic nerve by sutures and assessing pain
True or False, TLR4 is associated with allodynia. Provide justification
True. The gene encoding for TLR4 was compared in mice with this gene and knockout mice without this gene. They found absence of allodynia in knockout mice
What is adoptive transfer and what does it demonstrate
Adoptive transfer is a process whereby immune cells are taken from individual and transfer to another individual. In doing this they found that cells from high pain patients can be transfered into individuals with pain and induce high pain. This was not applicable in when trying to transfer cells from no - low pain patients
In humans, how can mechanical pain be assessed? Just name the types and what kind of pain they assess
- Von frey for superficial somatic pain
- Cuff algometry for deep somatic pain
How does von frey work in testing pain in humans? Would you observe different responses for hyperalgesia and allodynia?
In hyperalgesia you would measure pain via pin pricking pain and observe the response while in allodynia you would test multiple filaments and observe the threshold or response frequency
How does cuff algometry work
You place computer control pneumatic torniquet cuff on a patient and rise pressure until the individual begins to feel pain (detection threshold) and the till they can stand pain anymore (tolerance threshold)
In humans, how is electrical pain assessed? Describe this process.
Painful cutaneous electrical stimulation which works by placing electrodes on skin and increase the intensity to record pain threshold and tolerance. This directly activate nociceptive fibres and bypass nociceptors.
In humans, how is chemical pain assessed? Just name them.
- UVB inflammatory pain model
- Capsacinin
Describe how UVB inflammatory pain model works for assessing chemical pain
Hyperalgesia - Firstly you induce skin erythema by UVB irradiation and then follow up by performing thermal, pressure, and mechanical pain tests and observe differences in UVB treated and untreated
How does capsaicin work for inflammatory pain?
Assess hyperalgesia and allodynia by topically applying or injecting capsaicin which binds TRPV1 and cause neurogenic inflammation - this is a good for testing analgesics.
What’s the differance between detection threshold and pain tolerance
Pain detection threshold is the stimulus intensity and pain intensity at which an individual will begin to feel pain. Whereas, the stimulus tolerance threshold is the stimulus intensity/duration that a patient can no longer tolerate the pain
what is stimulus response curve in response to normal pain, analgesics and hyperalgesia & allodynia
An analgesic prevent perception of pain and this the detection and tolerance threshold will be moved to the right indicating a reduced ability to detect a pain stimulus and a greater tolerance to that stimulus
Following injury where their may be hyperalgesia and allodynia, the pain detection and tolerance threshold moves to the left. This is because there is increased sensitisation to pain and so detection is much more sensitive and tolerance is weak.
Describe the key components of the human endotoxin-capsaicin model
Intradermal injection of capsaicin (TRPV1) into arm with a low dose intravenous endotoxin (TLR4) 3 hours prior. Measure areas of allodynia with brush and puncate hyperalgesia using vonfrey and flare which is visual. Provides neuropathic pain model and also shows clinical evidence for TLR4 potentiation of pain
Describe the major benefits and limitations of one- versus multi-dimensional clinical pain scales.
One dimensional is simple, efficient and minimally intrusive however they asses limited parts of pain experience. - Multidimensional looks at sensory, affective, temoporal, location and intensity eg. McGill pain questonaries but are time consuming and hence used less.
