Week 5 Pain + Temperature + Itch

Question 1

Temperature

Answer 1

• Thermoreception: thermal energy, thermoreceptors on tips of A(delta) and C fibres of peripheral nerves
• Thermoreceptors: certain members of the TRP receptor superfamily act as thermoreceptors, other receptors/ channels also contribute towards thermoreception

Question 2

Pathway for Temperature

Answer 2

• Thermoreceptive signals travel to the brain via the spinothalamic pathway
• Immediately synapses and crosses over in spinal cord before ascending to the thalamus and synapsing onto primary somatosensory cortex
• Pain and temperature pathway

Question 3

Fibers

Answer 3

• A-alpha fibres: Myelinated, fast condution velocity, Proprio
• A-beta fibres: Myelinated, fast conduction velocity, Mechano
• A-delta fibres: Partially myelinated, Nociceptive + thermos
• C fibres: Unmyelinated, slowest conduction, Mechano + noci + thermo, Polymodal, As sensation starts to get painful, starts to activate C fibres as well

Question 4

TRPs

Answer 4

-ThermoTRPs have different activation thresholds allowing perceptual distinctions
between warm-hot and cool-cold
-Many of these receptors/channels are activated by thermal energy changes and also by certain chemicals
-TRPs found all over the body – cutaneous
-As you get colder/hotter starts to activate another receptor, and so on successively

Question 5

Chemosensory system

Answer 5

• The feeling elicited by certain chemicals – chemesthesis: Chemicals activate thermoreceptors and/or nocireceptors on FNEs
• Qualia associated with chemesthesis
• The chemosensory system is usually discussed in relation to the face
• CN V innervation
• Functions as a safety surveillance system
• Growing interest in all TRPs

Question 6

The chemosensory system is usually discussed in relation to the face

Answer 6

-CN V (trigeminal) innervated the skin of the face, nasal cavity, mouth, cornea
and conjunctiva of the eye: Innervation around eye is sensitive to chemical stimuli (low threshold),
Thinner barriers in mucus layers of mouth, nose and eye – easy to activate FNE in trigeminal system,
Other branches of nerve require higher concentrations, Skin’s protective layer makes it least sensitive to these stimuli,
Most of the body is underneath skin layers – FNE way under, To get a chemical to the FNE have to get through the skin
-CN IX (glossopharyngeal) and X (vagal) also carry chemosensory info that is
non-tastant induces (more pharyngeal + bronchial): Get coughing and sneezing reflexes

Question 7

CN V innervation

Answer 7

-3 branches: First 2 are sensory, 3rd in jaw is sensory and motor
-Somatosensory, mechanoreceptive info travels via CNV: Basic touch, mechanical compression
-Any sort of chemicals coming in – activate channels – change in ions - signal
transduction – up nerve in CNS
-People with a lot of FNE tend to be supertasters – very sensitive

Question 8

Functions as a safety surveillance system

Answer 8

-Initiates protective mechanisms: Tearing, mucus, salivation, coughing, sneezing, vasodilation/flushing, Body recognises that CNV activation means there is an irritant in the
area – get it out of system, Move away from unpleasant state – learning
-With repeated application of stimuli: Hyperalgesia – same stimulus causes more pain each time – don’t
adapt but sensitisation occurs, Allodynia – innocuous stimulus can result in pain – something not
usually painful, Sunburn – touching skin hurts, something that shouldn’t hurt
you causes pain
-Inflammation: ATP can recruit inflammatory response in blood, Further sensitisation – if you are around the stimulus enough to get
inflammatory response, Leads to hyperalgesia (with painful stimuli) and allodynia (with
innocuous stimuli)

Question 9

Anterior insula and anterior cingulate cortex

Answer 9

• Emerging idea that these region act as nodes of a salience network which helps flip
  between default mode network (DMN) and the central executive network (CEN)
• Activated in situation where there is salience, importance – information that could
  be important

Question 10

Thermo- and nociceptor activation

Answer 10

• Can trigger automatic behavioural responses
• Can trigger volitional behaviour responses: activation of AI + ACC, Switch to CEN
• Pain triggers things
• If chronic can become debilitating

Question 11

Nociception

Answer 11

Pain is:
o An unpleasant sensory or emotional experience associated with actual or potential tissue damage or described in terms of such damage
o Something is going to happen or has already happened

Question 12

Trigeminal relay pathway

Answer 12

Question 13

Types of Pain

Answer 13

o Nociceptive
– abrupt/strong cutaneous sensation, tissue damage, Cutting finger, bruising arm
o Neuropathic
– damage to neural structures, neural supersensitivity, Peripheral nerve is damaged, viral infection causing pathological
change in nerve causing it to misfire
o Psychosomatic
– physical pain of psychological origin, Perception comes from cortical activity, If you have pain pathways activating that mimic pain perception it can
cause pain

Question 14

Nociception and Thermoreception

FNE

Answer 14

o Have receptor channels on the ends of FNE similar to Thermoreception
o Overlap between thermo and pain info
o As it gets hotter and more receptors are activated the perception becomes
pain: It feels really hot but also feel painful, Cold pain is indistinguishable from hot pain

Question 15

Nociceptors vs mechano- and thermoreceptors

Nociceptors differ in some key ways:

Answer 15

• Slower conduction velocities
• All diffuse receptor fields
• Much higher thresholds for activation: Compared to mechano and thermoreceptors, Increase stimulus

Question 16

Process of nociception

Answer 16

1. Nociceptive stimuli activate nociceptors on FNE, this causes signal transduction
2. Resultant neural signal travels along nociceptive fibre to dorsal root ganglion and
   into spinal cord
   o Recall A delta fibres partially myelinated, C fibres unmyelinated
   o Get immediate sense of pain initially (A fibre) then a second, more dull,
   prolonged sense of pain (C fibre): Different myelination gives transmission differences – delay in info
3. Here in spinal cord, synapse to second order neuron + decussate
   o Come up through the same peripheral nerve as mechano info
   o Synapse straight away in the spinal cord and crosses over at that level

Question 17

Lateral spinothalamic pain relay

Answer 17

1. Nociceptors activated
2. Neural signal travels up to spinal cord
3. Synapse onto second order neuron in spinal cord
4. Second order neuron crosses midline and ascends all the way to the thalamus
5. Synapse onto third order neuron in thalamus, proceed to somatosensory cortex (SI)
   o Somatotopic map in SI – what is going on in the body and where
   - Nociceptive info from face travels via CVN and synapses ipsilateral brainstem, then
   thalamus, then SI
   - This lateral ST tract is the major pain pathway but there are others

Question 18

Pain info reaches the thalamus and then…

medial thalamus

Answer 18

o Projects to the frontal cortex (especially ACC and insula)
o This provides cognitive component
-Respond and formulate a plan – need to formulate response to avoid getting more injured
-Cognitive assessment – pain is happening and I need to do something about it

Question 19

Pain info reaches the thalamus and then…

Lateral thalamus

Answer 19

o Projects to SI and SII somatosensory cortex
o This provides sensory component
-Where/what/how much pain

Question 20

Cortical processing

Answer 20

• Numerous brain areas are activated during pain perception
• When you watch others in acute pain, non-sensory regions of the pain matriculates are activated in your brain: empathy, aversion
• People who have never felt pain- don’t have nociceptive pathways

Question 21

Pain + Spinal Cord

Answer 21

• The spinal cord plays an important role in the process of nociception:
  o Conduit for the information to travel up towards the brain
  o Potential site to stop/modify that info from traveling up to the brain
  -Decussation:
  o Signal travels up on different sides depending on what the info from the fibres is:Non-painful – goes all the way up to the medulla before crossing, Painful – crosses straight away

Question 22

Dissociated sensory loss

Answer 22

• If you damage the spinal cord, you may differentially affect mechanoreception and
  nociception, at different sites of the body
• Recall:o Each level of the spinal cord received info only for a specific dermatome
  o Each peripheral nerve enters the dorsal spinal cord, and then info ascends to
  the brain

Question 23

Bilateral damage at T3

Answer 23

o Lesion crosses entirety of the ‘motor way’
o Any info that comes into the T3 root will be blocked
o Lose all sensation in that T3 dermatome and anything below

Question 24

Unilateral damage at T3

Answer 24

o Dissociation comes when damage is only to one side
o From side of damage:
-Info from peripheral nerve can’t ascend from T3
-Lose everything from that half of the dermatome
-Any mechano will be blocked
-Lose mechano from that site and below
-Still have pain perception from below as it crosses over
o From opposite side
-On other side of body at T3: Opposite dermatome is blocked, Get no pain info, Still get touch info
-From below T3 on opposite side: Get no pain info, Still get touch info, Due to crossing over at different levels

Question 25

Gate Theory of Pain

Answer 25

-Processing within the spinal cord
- Within the spinal cord there are mechano and nociceptive fibres but also populations
of interneurons that facilitate or inhibit incoming information -Gate cells and transmission cells within spinal cord
When non-nociceptive touch info arrives in the spinal cord, this activates the gate cell, which inhibits the T cell
-Lock on gate firm =gate opening inhibited
- When pain info arrives in the spinal cord, this inhibits
the gate cell, which disinhibits the T cell, allowing the T cells to actively transmit pain
-Releases lock on gate=gate opening allowed=pain sensation

Question 26

Gate theory of pain

Cells

Answer 26

• Transmission (T) cells
  -Transmit pain info onwards, up toward the
  brain
• Gate cells
  -Work to ‘gate’ the activity of the T cells, tonically inhibit the T cells

Question 27

Modifications of Pain

Answer 27

• If you can influence the gate you can influence pain perception
• uses top down modification + bottom up modifications and exogenous control

Question 28

Modification of pain

bottom up

Answer 28

o Increase cutaneous sensation to try and shut the gate
o From the periphery
o Turn on gate cell to stop transmission of pain – provide very stong
mechanoreceptive input
o Give yourself mechano stimuli
-Touch the area that hurts right away
-Rub and injury – shuts the gate within spinal cord
-Trying to activate gate cell to reduce T cell pathways

Question 29

Modification of pain

top down

Answer 29

o Send a message from the brain to shut the gate
o Signal from the brain
o Strong central signal telling gate cell to activate and inhibit T cell
 Subconsciously – brain initiates top down modification right away
 Consciously – central control component, send excitatory signal to
gate cell
 Activating pathway – people can block the pain, learned to
control descending pathways and activate it themselves
 Endurance sports – combat signals telling you to stop running
 Placebo to treat pain – if you think this will help, maybe
activate descending pathways and reduce ascending pain pathway
o Might be enough to actually reduce pain perception
o Pathway is descending from SI
 Descending pathways modulate transmission of ascending pain signals
 E-stim of descending path inhibits activity of 2nd order nociceptive
neurons (T-cells) and produces analgesia – reduction of pain
o Descending path contains enkphalin, endorphin and dynorphins
 Endogenous opioids
 Relief from pain
o Start to train people about the descending pathway to reduce pain
 If we can use non-prescription drugs it will be a good thing
 Effect is the same – activate descending pathway endogenously as
opposed to exogenously using opioids

Question 30

Modification of pain

exogenous control

Answer 30

o Use an exogenous drug to help shut the gate
o Descending pathway responds to opiate drugs – exogenous opioids
 Activate the same pathway – help shut gate in spinal cord

Question 31

Congenital insensitivity to pain

Answer 31

o Since birth, an inability to feel pain (insensitivity) or lack of responsiveness to pain (indifference)
o Sometimes accompanies by Thermoreception deficits
o Genetic mechanisms increasingly understood
 NaV1.7 mutations
 NaV1.9 variants
 Difference in sodium channels mean that nociceptors don’t work in
the normal way
o Peripheral neuropathy
 Something going wrong in the peripheral, before the spinal cord

Question 32

Pain asymbolla

Answer 32

o Nociceptive stimuli are felt in a sensory component but without the affective component there is less/no unpleasantness/suffering
 Can feel pain but neutral to it - indifference
o Common aetiology
 CNS pathology – something noticeably wrong in brain + spinal cord
 Surgical brain resectioning
 Remove part of cingulate or internal capsule – central
components causing pain perception
 Opioids, to a degree, also achieve a level of asymbolia
 Can become physically dependent – relief from psychological pain
 Work at descending pathway – activate receptors in brain to reduce responsiveness to pain in an affective state
 Less suffering, don’t really care – helps heal better
- Sensory limbic dissociation
o Si and SII both go to motor cortex but SII also goes to limbic system – give
emotional affective component of touch as well
o In pain it is bad, negative emotion associated
o If this becomes disconnected then you lose this limbic reaction to sensory
information - Pain matrix
o Need cingulate, insula, prefrontal and limbic (as well as SI and SII)
o They give cognitive components to respond and formulate a plan – also give
the qualia ‘this hurts’
o If there is disconnect it removes some of the sense of pain or significance of it

Question 33

Functions of pain

Answer 33

• Alerts you to tissue damage
  o A warning signal that tissue damage has occurred or is about to occur
   Don’t continue with the situation – have hurt your body somehow and
  need to deal with it
  o Very difficult to ignore that signal
  o Initiates an immediate behavioural response
  -Prompts behavioural change to ensure survival
  o In you: hyperalgesia
   Repetitive application of stimuli results in sensitisation
   A warning signal to stop doing this
  o In you: allodynia
   Normal touch stimuli becomes painful
   Leads to protection of injured area – allows healing
  o In others: physical help, attention, empathy
   Responses in other – come to help
   To help your survival

Question 34

Pain Perception

Answer 34

• We all have different pain thresholds – we all experience pain differently and we all
  handle pain differently
• Partly due to physiology
  -Partly due to physcholgy

Question 35

Pain Perception

partly due to physiology

Answer 35

o Degree of FNE innervation
 More = more sensitive
o Number and types of TRP receptors, NaV1 receptors, etc.  Encoded by genes
o Skin properties
 Have to get through layers of dermis

Question 36

Pain Perception

partly due to psychology

Answer 36

o Selected attention
 Attend to the painful sensations and fixate – makes it worse
 Makes you have a lower threshold to subsequent stimuli
 Don’t pay attention to it – alleviate threshold
 If there is something that is more pressing
 You don’t pay attention to the pain until afterwards when you are safe, then pain kicks in
 Reduce pain perception with distraction
 Provide distracting stimuli – draws attention away from pain
o Socialreferencing
 Inbuilt idea of conforming to social norms
 From the moment something painful happens to us as infants – a baby
looks to those around them to see how to react
 Male – suppress crying from pain more than a female
 Societal norms – how we should respond based on age, gender
o Emotional state
 Mood – nervous, happy, sad
 Affects how you perceive pain, how you handle it
 Anxious – stimulus is more painful
 Fear – expectation of pain will enhance the perception
 Look away from the needle or look towards is to know where the pain is coming from
 Knowing it and mitigating it helps not feeling the pain as much
 For others it will exacerbate the pain due to the fear
 Negative affect – bad mood – things are more painful
o Noxious stimuli applied following induction of a sad mood are more painful
o Pain thresholds generally lower following exposure to negative slide scenes
 Mood effect the emotional aspect of pain perception
o When in pain you usually feel sad – makes it worse
o Personality traits
 Lifelong personality differences
 Do you carry trait anxiety, neuroticism?
 When you do experience pain do you suck it up, go home and cry,
make a huge drama
 Suppress it or play it up – subconsciously or consciously
 Pain elicits behavioural responses in other people – we know this and use this
 Catastrophizing chronic pain
 Intensification of emotional and cognitive components of pain
perception (overwhelmed, judging tasks unachievable)
 May elicit social support but is counterproductive … increases distress and fosters disability
 Intensifies affective component
o Sensory experience may not change but alters cognitive
component
 Usually is underlying pain – makes it very well known to other
to a greater degree
 Munchausen syndrome
 Psychiatric syndrome of feigning illness/disease to gain
attention
 Munchausen-by-proxy transfer to use of children to fulfil
psychological need for attention
 Nothing is wrong and you know this
o Make it up to get behavioural reaction from other o Do the research to feign the right symptoms to get
attention in clinical setting

Question 37

How do you treat pain when nothing is wrong

Answer 37

• No obvious bottom-up mechanism – nothing in periphery that should be causing
  pain
• Treating pain is one of the biggest challenges in modern medicine
  o Nociceptive pain
  o Neuropathic pain
   Can’t see what is going on
   In peripheral nerves in spinal cord
   If something is wrong in the pathway – abnormal activity firing, causes
  pain
  o Psychosomatic pain
   Nothing cutaneously wrong, or peripherally or centrally
   Something psychologically manifesting as physical pain
   Treating this is a particularly tough challenge
   Historically viewed with scepticism
   Finally seeing a shift in medicine: pain can be top-down
   If you activate pain matrices in the brain, pain qualia will result
   Need to treat this

Question 38

Pruitus

Answer 38

• Itching = an unpleasant sensation that evokes the desire to scratch
• Acute pruritus is useful – tells you something is on the skin
• Chronic pruritus can be miserable
  o Pruriceptive
   Something wrong cutaneously
   Something causing the itch – bite, rash
  o Neuropathic
   Abnormally firing in the pathway that carries itch
  o Psychogenic
   Something wrong psychologically, manifesting physically as itch
  o Systemic
   Things that go wrong in the body that manifest as itchiness
   Renal failure, thyroid, bile
   Side effect of itch
• Itch appears to stem from activation of specific A delta and C fibres that express certain receptors/combinations of receptors
  o H1 histamine receptors – activated by histamine
  o TRPV1 + H1 histamine – activated by capsaicin and histamine o MrgA3 receptors – activated by chloroquine
  o 5-HT2 serotonin receptors – activated by 5-HT

Question 39

Should itch be its own modality? Submodality?

Answer 39

• Pruritogens (stimuli) activate specific types of receptors on FNEs (A delta and C
  fibres)
• This results in signal transduction
• Unique neural relay?
  o Uses spinothalamic – a shared pathway with nociception and Thermoreception
• Unique cortical processing
  o Pruritogenic stimuli cause activation in  SI
   Need to know where you’re itching and how much
   Is it itch vs mechanoreception or pain
   Motor areas
   Pre-supplementary motor area, SMA itself, M1 o Makes sense when you think about the response we have
   We scratch – definitive loop
   The minute we feel itch we scratch and move away
   Itch-scratch cycle - Itch is perceptually intriguing
  o The qualia seems to be easily elicited by the idea of itch
  o Just the mention of it, verbally, visually – can cause qualia
  o Is this a blurring of perception and conception? Is it inception – causing it in
  someone

Question 40

Week 5 Pain + Temperature + Itch