Week 5 Pain + Temperature + Itch Flashcards
Temperature
- 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
Pathway for Temperature
- 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
Fibers
- 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
TRPs
-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
Chemosensory system
- 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
The chemosensory system is usually discussed in relation to the face
-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
CN V innervation
-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
Functions as a safety surveillance system
-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)
Anterior insula and anterior cingulate cortex
- 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
Thermo- and nociceptor activation
- 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
Nociception
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
Trigeminal relay pathway
Types of Pain
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
Nociception and Thermoreception
FNE
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
Nociceptors vs mechano- and thermoreceptors
Nociceptors differ in some key ways:
- Slower conduction velocities
- All diffuse receptor fields
- Much higher thresholds for activation: Compared to mechano and thermoreceptors, Increase stimulus
Process of nociception
- Nociceptive stimuli activate nociceptors on FNE, this causes signal transduction
- 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 - 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
Lateral spinothalamic pain relay
- Nociceptors activated
- Neural signal travels up to spinal cord
- Synapse onto second order neuron in spinal cord
- Second order neuron crosses midline and ascends all the way to the thalamus
- 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
Pain info reaches the thalamus and then…
medial thalamus
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
Pain info reaches the thalamus and then…
Lateral thalamus
o Projects to SI and SII somatosensory cortex
o This provides sensory component
-Where/what/how much pain
Cortical processing
- 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
Pain + Spinal Cord
- 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
Dissociated sensory loss
- 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
Bilateral damage at T3
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
Unilateral damage at T3
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
Gate Theory of Pain
-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
Gate theory of pain
Cells
- 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
Modifications of Pain
- If you can influence the gate you can influence pain perception
- uses top down modification + bottom up modifications and exogenous control
Modification of pain
bottom up
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
Modification of pain
top down
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
Modification of pain
exogenous control
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
Congenital insensitivity to pain
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
Pain asymbolla
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
Functions of pain
- 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
Pain Perception
- 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
Pain Perception
partly due to physiology
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
Pain Perception
partly due to psychology
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
How do you treat pain when nothing is wrong
- 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
Pruitus
- 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
Should itch be its own modality? Submodality?
- 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
Week 5 Pain + Temperature + Itch
