Somatosensory & pain systems Flashcards
What is pain?
Derives from POENA(L) & means penalty or punishment = suffering, distress of body or mind
Sensory & emotional, makes u feel bad w the emotional component
Define pain exactly:
“An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”
Why does the deifinition of pain mention it resembling pain?
“An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”
“Or resembling that associated with” = lots of ppl in pain aren’t actually suffereing from an obvious cuase
Where are our thresholds for pain set (e.g. mechanical or thermal) & why?
Series of sensory thresholds that are set just below where the tissue damage would occur
This is a survival mechanism –> bc if the tissue is damaged it may become infected etc
What is nociception?
The perception (detection) of noxious events in our environment
Has no emotional component to it, need this to drive the emotional component of pain
What is pain?
The “feelings” associated with nociception
What are the 3 things that pain always is?
- Subjective
- A learned experience
- UNPLEASANT
What do we mean when we say pain is subjective?
Everyone experiences pain differently
e.g. Could be suffereing from severe arthritic damage & be experieincing very little pain while other would experience a lot
What do we mean when we say pain is a learned experience?
We need to experience pain thru childhood to learn how to process pain
Pain experiences when you’re younger influence your pain response when ur older
However pain during critical stages in child development can alter developemnt
How can pain during critical stages in child developemnt alter pain reception?
Children who go thru surgery when young, have dampened pain reception (e.g. thresholds are higher)
However if they’re re-injured they feel more pain & are more susceptible to chronic pain later in life
What NS in involved in pain?
Both the PNS & CNS
What is the overall role of the PNS in pain?
Detection of noxious events (nociception) involves the PNS which relays info to the CNS (specifically the spinal dorsal horn)
What is the overall role of the CNS in pain?
Interpretation of noxious inputs takes place in the CNS (specifically in the brain)
Is the brain needed for reaction to a painful stimulus?
No - brain is for interpretation of noxious info
Reaction to painful stimulus this is not needed –> brain & SC can be seperated
The body will still react as the unconscious reaction does not req the brain but the reaction to how it makes us feel involves the brain
What are nociceptors?
Peripheral nerves that detect noxious stimuli
Are activated by intense chemical, thermal or mechanical stimuli
& They feed that info into the dorsal horn of the spinal cord
Where is the ventral & dorsal horn of the SC found?
Dorsal = at the top
Ventral = at the bottom
Where does info enter & exit the SC?
Dorsal horn = info enters the SC thru here at the top
Ventral horn = reflexes flow out of here at the bottom
What is the main focus/role of the dorsal horn of the SC?
Pain & nociception
This is where the sensory info arrives, info is relayed from here up to the brain & the brain in turn sends the info back down the SC, thru to the ventral horn
If the dorsal horn is more/less excited what do you feel?
More excited = more pain
Less excited = less pain
How do analgesics work to dampen pain?
They dampen excitement in the dorsal horn of the SC
Less excitement = less pain felt
What are the elements of the “pain pathway”?
- Peripheral nociceptors
- Primary afferent neurons
- Intrinsic spinal dorsal horn neurons
- Ascending projection neurons
- Higher centre neurons
- Descending neurons
(Works like a circuit)
What are the 3 types of pain reception fibres?
- A-beta fibres
- A-delta fibres
- C fibres
How big are A-beta fibres & why is this helpful?
Have the largest diameter & are wrapped in lots of myelin, so they conduct quickly by saltatory conduction
What sort of signals so A-beta fibres carry?
Transduce & encode info abt light touch, pressure, vibration & some pain
Use these most when interacting with stuff in our environment
What is the stucture of A-delta fibres like?
Myelinated like A-beta, but less so
Smaller in diameter than A-beta too
What sort of info do A-delta fibres carry?
Convey info such as sharp pain or fast pain, also temp & touch
What is the structure of C-fibres like?
Thin & unmelinated
So slower conduction
What are C-fibres activated by?
Activated by high threshold info, so high temp & dull pain
What NTs do A-beta & A-delta fibres use?
ATP & glutamate ATP
What NTs do C-fibres use?
They also use ATP & glutamate like Delta & Beta
However, a subset of C fibres use neuropeptides –> CGRp & substance P
Give an example of an area that uses C fibres for pain
Testicles –> these are only activated by C fibres, thats why there is a prolonged aching pain
How does C fibres use of neuropeptides (CGRp & substance P) help their function?
CGRp & substance P are slow acting NTs so they hang around for a while
This creates a dull aching pain in the affected area, like when you stub your toe & it hurts for a while after
Where are the 2 terminals of peripheral afferent neurons found?
One in dorsal horn in the SC
One in the distal terminal in the target tissue (e.g. in the skin)
How many terminals do peripheral afferent neurons have?
2 terminals
Name some of the distal terminals found in the skin (epidermis)
Epidemis:
- Free nerve endings
Sub-epidermis
- Meisner corpuscle
- Root hair plexus
- Merkel disks
Dermis:
- Pacinian corpuscle
- Klause’s end bubbles
Describe the pain response that happens when you stub your toe:
- Initially A-beta fibres you feel pain from stubbing ur toe
- Shortly followed by A-delta fibres which is sharp pain & then a second(ish) later..
- C fibres will arrive, which is the slow, dull & achy pain
What are primary afferent fibres (PAFs)?
Are the neurons which innervate our skin, muscle, viscera & bones
What are the 3 types of PAFs?
- A-Beta
- A-Delta
- C fibres
What are the properties of A-delta & C-fibres?
- High threshold
- Can respond to single or multiple modalities
- Activation leads to different qualities of pain
- Have specific transduction channels responding to noxious stimuli
- Can have both afferent & efferent functions
What are the 5 key parts of the spinal cord when looking at pain?
- Dorsal horn
- Ventral horn
- Superficial laminae
- Intermediate laminae
- Deep lamina
What is the superficial laminae in the SC made up of?
Pain specific neurons
Pain inputs from c-fibres, A-delta fibres, interneurons & projection fibres that process painful info
(Top 2 layers)
What is the intermediate laminae in the SC made up of?
Touch specific neurons
Receive input from A-beta fibres so process tocuh specific innocuous info
(Layers 3&4)
What is the deep lamina in the SC made up of?
Intergrative neurons
Deepest part of the spinal cord is intergrative - get info from all 3 sensory neurons types
(Layer 5)
What appears white & grey in SC stains?
White - myelin
Grey - neurons
What flows thru white matter in the SC?
Neurons that are myelinated carrying info up to brain
How many layers (laminae) are there in the grey matter of the SC?
We have 10 laminae (layers)
What are the 10 laminae in the SC grey matter divided into?
- Superficial laminae (top 2 layers)
- Intermediate laminae (3&4)
- Deep lamina (layer 5)
What is the spinal cord dorsal horn the site of?
It is the first site of processing cociceptive info
Describe how the dorsal horn is innervated:
- Peripheral nerves have their cell bodies in the dorsal root ganglia - adjacent to but outside the SC
- Sensory neurons innervate their target tissue & the dorsal horn of the SC entering via the dorsal root
- Different types of sensory neurone terminate in different parts of the dorsal horn
Why would be lamina 1&2 but also 3&4 be activated during a high magnitude noxious stimulus?
Noxious stimulus will activate lamina 1&2
3&4 will be activated too bc pain will also activate the low threshold fibres
High magnitude stimulus will activate all fibre types so you see bigger vol of dorsal horn being activated
What happens in the SC when a noxious stimulus is detected?
- PAFs synapse w doersal horn neurons (second order neurons)
- These are either projection neurones or spinal interneurones
- Projection neurones convey info to the brain
- Interneurones relay & intergrate noxious info to projection or motor neurones
What is the best way of classifying projection & interneurones?
Based on the NTs the neuron releases & other proteins they express (may produce nitric oxidr for example)
(Not best for them to be classified by apperance or electrophysiological properties as they aren’t always consistent or easy to detect)
What happens when the PAF arrives at the dorsal horn?
When it arrives it will send an axon into the dorsal horn –> but it doesn’t make synaptic connection w just 1 second autoneurone
May contact 1000s of autoneurones –> projections ficate in many ways & make connections in a large vol of dorsal horn tissue
Why is there a large amt of substance P found at the top of the dorsal horn?
Many C-fibres enter here in the dorsal horn & C-fibres produce lots of substance P
What is the receptor for substance P?
NK1 receptor
(Neurokinin 1)
Where do each of the nociceptors terminate in the laminae of the dorsal horn?
A-Delta = I & V
C = II & V
A-Beta = III, IV &V
How does nociceptive info get to the brain?
Uses projection neurones –> summarises the 3 main concs of neurones that form the spinothalamic tract
Where are projection fibres found in the SC?
Some in lamina 1, a few in 3&4 & LOTS in lamina 5
How do projection neurones work?
Their cell bodies are found in the SC but they send axonal projections all the way up to ur brain
Where do the projection neurones in the SC send info to & why?
The thalamus
It is a relay & distribution centre for all physical info –> makes sure info is sent to the correct bit of the cerebral cortex
Where would somatosensory info in the spinothalamic tract go to?
Somatosensory info in the spinothalamic tract recieves info from the SC
The part of the thalamus that receives it sends it to e.g. the somatosensory cortex or the anterior cingulate cortex
How does pain info flow thru the brain?
- Info arrives in the thalamus
- It sends info to the primary somatosensory cortex
- In turn it sends info to the secondary somatosensory cortex (thalamus would also send info directly here too
- Thalamus also sends info to anterior cingulate cortex & the prefrontal cortex
What are the anterior cingulate cortex & the prefrontal cortex involved in?
The more conscious perception of emotions of pain (how we feel in the long term)
What is the role of spinoparabrachial tract?
Another ascending tract - this is the main one involved in the emotion of pain
How does the spinoparabrachial tract send emotional info about pain & how is the response generated?
- It sends info from lamina I & lamina II (bits of the dorsal horn that get the pain info)
- Sends info up to PARABRACHIAL NUCLEUS (has large output to amygdala)
- AMYGDALA activated when soemthing unpleasant happens, in turn sends info to the BASAL GANGLIA
- THALAMUS sends info to the INSULA
- CEREBELLUM is also involved in pain processing (not just coordianting movement)
What is the role of the parabrachial nucleus?
Not involved in where in my body I’m hurt but how does it make me feel
(Has a large output to the amygdala - involved in fear and aversion)
What is the insula?
It is an interaction point between sensory & emotional points of pain
It is incredibly important
What are the 2 main factors that can affect how much you feel pain?
- Attentional modulation
- Emotional modulation
How does emotional modulation affect the way you feel pain?
If u have low mood u will feel pain more intensely that if ur happy
Good mood = less pain
Your emotional brain centres are able to modulate the way you feel pain
What is attentional modulation & how does it affect how u feel pain?
The attention you pay to the pain affects the way you experience pain
If ur the sort of person that catastrophises things & you worry too much about the pain it will feel worse
If ur distracted pain = less
Babies pain perception:
Low cortison babies (less stressed babies) feel less pain –> proves this is not just true in adults
Could test cortisol in their saliva
Describe the periaqueductal grey (PAG):
Midbrain centre involved in descending pain modulation
Involved in sending info back down the SC, not just to do with movement but to do w modulating the excitability of the dorsal horn
What is the earliest evidence of the PAG?
From Mayer & Price –> they electrically stimulated the PAG of rats
Rats elicited stimulation produced analgesia
Following the noxious stimulus they didn’t try to move away or squeal
They managed to completely remove thier experience of pain
Works the same in humans
Why can’t we use electrical stimulation of the PAG as a therapy option for pain?
Although it removes our experience of pain when stimulated
The PAG is also invovled in more than jsut pain responses –> involved in many AUTONOMIC proesses
e.g. HR, BP, respiration rate
Can’t be used as a theraputic option
Where is the PAG found in ur brain?
Lies right in the centre of our brain, next the the periaqueduct & appaears grey, hence the name
Name some of the inputs into the PAG:
Gets info directly from the SC but also from the;
- Cingulate cortex
- Frontal cortex
- The hippocampus
- Amygdala
- Hypothalamus
What is the main role of the PAG?
Much like the thalamus is a relay centre for info coming into the brain;
The PAG is a relay centre for info leaving the brain
Describe the connectivity of the PAG:
PAG intergrates inputs from the limbic forebrain & diencephalon –> w inputs from dorsal horn or SC
Major inputs arise from;
Amygdala, prefrontal cortex (anterior cingulate & insular cortices), nucleus accumbent, hypothalamus, locus coerulus & dorsal horn of SC
What can microinjection of opiods or electrically stimulating the amygdala cause?
This results in analgesia
Can be reversed by lidocaine injection into the PAG
What can happen in you have a stroke occur in ur thalamaus or PAG?
Obvious effects such as issues w speech & movement
But it can also cause abonormal processing of pain –> bc the lesions occur in the area of the brain which impacts pain processing
What is the dorsal part of the PAG involved in?
More autonomic functions
What is the ventral part of the PAG involved in?
More invovled in pain modulation
How does the PAG connect to the SC?
PAG controls the dorsal horn Does but does not connect directly to the SC
PAG sends projections to a part of the braintem called the rostral ventral medulla
This sends neuronal projections down to the dorsal horn
Where do the specific areas of the PAG project to & how does this relate to their roles?
- Ventrolateral PAG (pain modulation) projects to the rostral ventral medulla (RVM) & to the dorsal lateral & ventrolateral pontine tegmentum
- Dorsolateral PAG (autonomic functions) projects to the ventrolateral medulla, a region critical for autonomic control
- Rostral PAG projections also exist particularly to the medial thalamus & orbital frontal cortex - areas involved in ascending nociceptive pathways
What is the role of the rostral ventral medulla?
Sends projections down the breain stem between the PAG & dorsal horn
What recent development has been made on the PAG?
Shown recently that specific regions of the PAG recieve input from specific regions of the dorsal horn;
e.g. second order neurones activated by C-fibres projected preferentially to the VL-PAG, whereas larger A fibres projected mainly to the DL/L PAG
What is the rostral ventral medulla (RVM)?
The rostral part of the ventral medulla
Not a specific brain region like nuclues accumbens or the thalamus –> RVM is an area
AKA the nucleus raphe magnus (NRM)
Where does the RVM (NRM) recieve a major input from?
The PAG
The RVM then sends projections down to the dorsal horn of the SC
What happens if you activate the RVM (NRM)?
Activating the RVM can make pain better by inhibiting the excitability of the dorsal horn
(can make pain worse too by facilitating excitability in the dorsal horn)
Brain bidirectionally controls the way we experience pain
Name 3 areas that contain opioid peptide transmitters (e.g. enkephalins)?
- PAG
- NRM (RVM)
- Dorsal horn
What % of the pop suffer from chronic pain?
25-30% of the pop in developed countries experience chronic pain
Chronic pain = ?
NOT USEFUL (maladaptive)
Define hyperalgesia:
Inc responsiveness to a normally noxious stimulus
If stimulus hurt before it will rlly hurt now
Define allodynia:
Pain or unpleasant sensation evoked by a normally non-painful stimulation
Define spontaneous pain:
Pain w no obvious immedaite cause
What causes chronic pain?
Arises from damage to tissues (inflammation) or nerves
The cause of pain may have gone but the SC is still sending signals of this pain
Physiological properties of the SC ahve undergone change & means pain is felt all the time
(Changes in perception arise thru changes in neuronal properties)
Why is spontaneous pain so bad?
You can’t escape spontaneous pain, chronic pain makes u miserable & is a vicious cycle:
Can lead to social isolation as the pain in public makes you withdraw, then alongside the physical pain u feel u also feel emotional pain,
e.g. low mood or anxiety, we know when your mood is worse you feel pain more & you also think about the pain all the time (attention to pain).
What can be used to treat chrionic pain short term?
Opioids (these dampen the pain signals firing in the dorsal horn)
Why can opioids only be used short term to treat pain?
They become ineffective after a short period of time –> higher dose is needed
This can lead to addiction
What are the characteristics of primary hyperalgesia?
- Thermal (heat & cold), and mechanical hyperalgaesia & allodynia
- Small region surrounding injury
- Within minutes
- Peripheral neuronal changes
(Response to a painful stimuli)
What are the characteristics of secondary hyperalgesia?
- Mechanical hyperalgesia & allodynia
- Larger region
- Within minutes/hours
- CNS changes
Why have we developed the system of secondary hyperalgesia?
To protect us from further injury
Our thresholds are lowered in the larger zone so the chances of us being injured further in the primary region is reduced
