7. Anatomy and physiology of pain Flashcards
Define pain
An unpleasant sensory and emotional experience associated with actual or potential tissue damage
Pain is a perception - not always associated with tissue damaging stimuli
“It is what the patient says it is” - open to interpretation due to different levels of pain thresholds
What are the four different mechanisms of pain?
Transduction - noxious stimuli translated into action potentials
Transmission - action potentials propagate along pain pathways
Perception - discrimination of the type of pain
Modulation
What is a nociceptor?
A primary afferent i.e. a sensory receptor for painful stimuli
Brings informtion to the nervous system from peripheral axons in the skin
What are the different types of axons in the nociceptive system?
C fibres - unmyelinated - slow conducting (<1m/s-5m/s)
A delta fibres - very thin myelinating fibres - fast conducting
Explain the idea of first pain and second pain
E.g. touching a hot stove
First pain - transmitted via the a delta fibres - fast response to the pain to allow you to move your hand away from the hot stove
Second pain - slower response - more visceral, intense, emotional pain - the burning of your hand a while after touching the stove
What is transduction in the nociceptive system?
The transmission of pain sensation to action potentials
How does transduction occur from noxious stimuli?
Nociceptors have free nerve endings within the tissues i.e. are not surrounded by capsules
Within the terminals, there are different ion channels which open in response to different stimuli e.g. TRPV1 opens in response to noxious heat and thermal stimuli and TRPM8 in response to cold stimuli
The stimuli must first reach the threshold before an action potential can be generated and reach the spinal cord - graded stimuli
Which fibres are damaged in diabetic neuropathy and how does this result in the symptoms of the disease?
C-fibres are damaged
There is no impulse to move the legs during e.g. sleep when uncomfortable
This can result in pressure sores, gangrenes, loss of blood supply
What are the two main classes of C-fibres and how do they differ?
- Peptidergic c-fibres
These release peptides peripherally and centrally
Promote inflammation in the peripheral release - increased inflammatory cells to aid clear up of injury - Peptide-poor c-fibres
Have distinct receptors to allow the release of ATP into the injured skin
More involved in mechanical stimuli
To which lamina do the nociceptor fibres project to?
C fibres project to lamina I and II (and V)
A delta fibres project to lamina I and V
Lamina I - where all nociceptors project to
Lamina II - where interneurones are found (can be excitatory or inhibitory)
Lamina V - mixing of information occurs here - not just from nociceptors
Where does the spinothalamic tract project to to mediate the majority of the sensation of pain?
Projects to the limbic system of the forebrain via the brainstem and the posterior medial thalamus
Nb. the pain also stimulates general arousal and focussing of attention on the painful region
What are projection neurones?
These are second order neurones - carry the pain message onward from the primary afferent neurone
These decussate close to where the nociceptors enter the spinal cord and form the spinothalamic tract
What are the two parts of the spinothalamic tract?
Anterior spinothalamic tract
Lateral spinothalamic tract
What is the function of the anterior spinothalamic tract?
The anterior spinothalamic tract is the one carrying the majority of the adelta neurones going to lamina V
Innervates the ventral posterior lateral (VPL) and the ventral posterior medial (VPM) (these are nuclei of the somatosensory thalamus) i.e. the lateral portion of the thalamus
VPL is very important for touch stimuli
Conveys first, discriminative aspects of pain e.g. ‘move hand’
What is the function of the lateral spinothalamic tract?
This is the tract carrying the majority of the c fibres (also carries some a delta fibres) and these mainly project to lamina I
Innervates the more posterior/medial parts of the thalamus and also some part of the cortex
Conveys second, punishing aspects of pain e.g. ‘ouch, that hurts!’
What is the amygdala?
This is a region of the brain important for the memory of pain - the association of pain to a particular event
What is the difference between fast and slow pain?
Fast pain - sharp pain conveyed by adelta elicits reflexive withdrawal to prevent further injury
Slow pain - burning, lingering, emotionally changing pain
How is our response to stimuli altered when there has been an injury and what is this known as?
When there has been an injury and slow pain has occurred, there is inflammation
This drops the threshold of pain of the nociceptors - something that was not painful in this region is now conveyed as painful
SO there is a reduced activation threshold and an increased responsiveness to the noxious stimuli
This is ‘Peripheral sensitisation’
What are the four signs of inflammation?
How can the reduced threshold of pain be remediated?
Calor (heat)
Rubor (redness)
Dolor (pain)
Tumour (swelling)
Via anti-inflammatory drugs i.e. NSAIDs
These target prostaglandins
What is central sensitisation?
This is where there is a prolonged nociceptor input to the CNS into the dorsal horn - the projection neurones become more active
The CNS is regulated in a persistent state of high reactivity
Low threshold pain stimuli can now activate the pain pathway
What is the neurotransmitter involved in central sensitisation?
The nociceptor afferents release glutamate which acts of NMDA receptors - leads to changes in the secondary messenger systems and reduces the pain threshold due to increased excitation
What are the hallmark presentations of sensitisation?
Hyperalgesia - increased sensitisation to noxious stimuli
Allodynia - increased sensitisation to all stimuli
Spontaneous pain
How do peripheral sensitisation and central sensitisation differ to each other?
Peripheral - involves increased inflammation and nociceptors and sensory afferents
Central - involves nociceptive input into the dorsal horn and CNS and projection neurones - occurs due to peripheral tissue damage or inflammation
What is chronic pain?
What is maladaptive pain?
Chronic pain arises from nociceptive pain and is adaptive, reversible and can heal
It is pain of more than 12 weeks usually associated with an underlying condition
Chronic pain can develop into maladaptive pain
This is a continued state of suffering - pain that persists past the healing phase following an injury
What are the different types of maladaptive pain?
Neuropathic pain - due to injury/dysfunction in PNS or CNS
Dysfunctional pain - no known lesion or inflammation
NB. normal analgesics are not effective
What causes maladaptive pain?
Anything that injures the CNS e.g. stroke, infection, drug treatments, diabetes
What is pain modulation?
The modulation of the level of pain - whether the stimuli is perceived as more or less painful
Where does pain modulation occur?
Occurs at all levels - cortex, brain/brainstem, spinal cord (central sensitisation), periphery (inflammation)
What is endogenous modulation?
This is at the level of the spinal cord e.g. acupuncture
Some other input stimulus (innocuous) to the same area can dampen down the pain (like if you wack your hand and then rub it to make it feel better)
The innocuous pain would normally act to dampen down the pain transmission - this is known as the gate control theory
Which neurones are responsible for pain modulation?
The interneurones located in lamina II
How does acupuncture work as endogenous modulation?
Thought to activate adelta fibres via Diffuse Noxious Inhibitory Control (DNIC) of pain
Thought to work via the gate control theory
What projections do neurones from the lateral spinothalamic tract have, other than to the cortex?
Has some extra projections:
Spinal circuitry - reflexes
Reticular formation - arousal and alerting cortex
Periaqueductal grey (PAG) in midbrain - descending pain modulation
Parabrachial nucleus in pons - limbic activation
Briefly describe the periaqueductal grey (PAG) pathway?
This is one of the pain pathways which can result in the sensation of neuropathic pain
Via the usage of serotonin and noradrenaline
What is the use of enkephaline in the PAG pathway?
The PAG contains enkephaline producing cells which suppresses pain
What are enkephalines?
These are endogenous opioid peptides and these bind to opioid receptors
How are prostaglandins produced in the body?
From arachidonic acid via COX-1 or COX-2
When is COX-1 present in tissues?
Normally always present in the tissues at low levels
When is COX-2 present in tissues?
COX-2 is induced during inflammation
What is the role of prostaglandins on c-fibres?
PGs sensitise the c-fibres by increasing the numbers of other receptors and opening a greater number of these
Which drugs target prostaglandins?
Analgesics
Anti-inflammatory drugs e.g. NSAIDs
SO what is the role of prostaglandins in the body?
These are producing during times of pain/damage and these mediate inflammation
What releases arachidonic acid?
Phospholipase A2
