Pain 1 Flashcards
What is nociception?
The sensory process that provides the signals that trigger pain
What is pain?
The feeling or perception of irritating, sore, stinging, aching, throbbing, miserable or unbearable sensations arising from a part of the body
What is congenital anaesthesia?
An inherited inability to feel pain
What is the morphology of nociceptors, where are they found?
Found in the periphery (dermal-epidermal border)
Simple free nerve endings - peripheral nerve terminates as naked, unmyelinated endings in the dermis
What is the basic mechanism of nociception?
Tissue damage and inflammation triggers the release of substances eg. prostaglandins, bradykinin and histamine that can sensitize peripheral nociceptors and induce hyperalgesia
What 3 substances are released by inflamed or damaged tissue which sensitize nociceptors?
1) Prostaglandins
2) Bradykinin
3) Histamine
Transduction of nociceptive stimuli occurs in the free nerve endings of which 2 types of fibres?
1) unmyelinated C fibres
2) thinly myelinated Ad (a delta) fibres
Some nociceptors are polymodal, however some only respond to one modality, what are the 3 possible modalities they can respond to?
1) Mechanical - respond to strong pressure
2) Thermal - respond to burning heat/ extreme cold
3) Chemical - respond to histamine or other chemicals
In what 3 ways does the brain respond to nociception?
1) Feels pain
2) Avoidance (motor fibres may leave spinal cord causing reflex withdrawal)
3) Emotional reaction
What are the 4 parts to the physiological basis of pain?
1) Activation of peripheral nociceptors that express heterogenous populations of receptors/ion channels
2) Transmission of impulses via a delta and c afferents to spinal cord
3) Projection to brain via ascending pathways
4) Subjective experience of sensory and emotional components of pain
Describe an experiment to distinguish between sensory afferents that subserve somatic heat sensation and nociceptive afferents that detect painful heat?
1) Thermal stimuli applied to receptive field of cutaneous receptor and nociceptor
2) Record afferent firing in response to incremental increases in temperature
3) Afferents that subserve somatic sensation do not increase there firing as the temperature goes beyond a painful threshold
4) Nociceptive afferents - don’t fire at lower temps but continue to increase firing as temperature goes above a painful threshold
Thermal and mechanical nociceptors have what kind of fibres?
A Delta fibre
Polymodal nociceptors have what kind of fibres?
C fibres
2 categories of pain have been described - first and second pain, which type of fibre is each carried by, what nociceptors detect each and what is the nature of each/
1st PAIN - Carried by fast a delta fibres - Sharp or prickling - Easily localised - Occurs rapidly with short duration - Mechanical or thermal nociceptors 2nd PAIN - Carried by slow C fibres - Dull ache, burning - Poorly localised - Slow onset, persistent - Polymodal nociceptors
How has the different role of a delta and C fibres in first and second pain been shown?
It is possible to selectively anaesthetise C fibres and A delta fibres to dissect out the role of each sensory afferent in pain perception
Cold thermoreception and sharp pain are carried by which type of fibres?
A delta
Warm thermoreception and burning pain are carried by which type of fibres?
C
Where are the bare nerve endings that detect warm and cold thermoreception located?
Deep epidermis
Where are nociceptors that detect pain located?
In the epidermis
Where are the cell bodies of nociceptive fibres located?
Dorsal root ganglion
Afferent terminals of nociceptive fibres enter the dorsal horn and travel up/down short distances in which tract?
Lissauer’s tract
Afferent terminals of nociceptive fibres synapse with neurons in which laminae of the dorsal horn, what is this called?
The superficial laminae - principally lamina 1 and 2, the substantia gelatinosa
Which 2 lamina make up the substantia gelatinosa?
Lamina 1 and 2
What is the mechanism behind referred pain?
1) Nociceptive afferents from internal organs (viscera) and skin enter the spinal cord through common routes and target overlapping populations of spinal neurons
2) The cross talk between the 2 leads to referred pain whereby visceral pain is perceived as having a cutaneous source by the sufferer
What is referred pain?
When visceral pain is perceived as having a cutaneous source by the sufferer
Oesophageal pain is often referred to where?
The chest wall
Heart pain is often referred to where?
Chest and arm
Bladder pain is often referred to where?
Perineum
Ureter pain is often referred to where?
Lower abdomen and back
Prostate pain is often referred to where?
Lower trunk and legs
In the early stages of appendicitis where is the pain referred to?
The abdominal wall around the navel
What excitatory neurotransmitter is released by pain afferents?
Glutamate
Aswell as glutamate what other type of neurotransmitter is contained within synaptic vesicles of pain afferents?
Neuropeptides
Name an important neuropeptide contained in synaptic vesicles of pain afferents?
Substance P
What is Substance P?
A neuropeptide which is a mediator of nociceptive synaptic transmission in the dorsal horn - it is most dense in the superficial dorsal horn
Neurons in the dorsal horn express what receptor for substance P?
Express the receptor NK1
Pain afferents synapse with neurons in the dorsal grey horn which project to where?
The thalamus
What are the 3 components of the ascending pain pathways?
1) Lateral spinothalamic tract
2) Spinoreticulothalamic tract
3) Anterior spinothalamic tract
In ascending pain pathways at what level do inputs cross to the contralateral side?
At the level of the spinal cord
What is dissociated sensory loss?
When different sensory modalities are lost in different areas of the body due to one lesion
Does Brown Sequard syndrome produce dissociated sensory loss?
Yes
In the trigeminal pathway primary neurons carrying pain sensation from the head, synapse in a part of the trigeminal nucleus called what?
Pars caudalis
Where do secondary axons in the spinothalamic and trigeminothalamic tract synapse in the thalamus?
Both in different parts of the ventral posterior nucleus
Spinothalamic - VPL
Trigeminothalamic - VPM
Axons also synapse in the small intralaminar nuclei of the thalamus
Functional Imaging of thermal pain can be performed using a PET scan to identify increased blood flow indicating increased activity to different parts of the brain in response to thermal pain - which 3 parts of the brain will be highlighted?
1) Part of primary somatosensory cortex
2) Insular cortex
3) Anterior cingulate cortex
The above 2 are part of the limbic system and associated with the emotional aspects of pain
Name a condition win which pain and touch sensations are experienced with no sensory inputs?
Phantom limb pain
Give 2 examples of when sensory inputs occur without pain sensations?
1) Endogenous analgesia
2) Pain modulation
What is hyperalgesia?
Increased pain
What is allodynia?
Touch-evoked pain (non noxious stimuli is extremely painful)
What percentage of amputees experience phantom limb pain?
50-80%
Can phantom limb pain be treated?
No it is highly resistant to treatment
What is the type of pain experienced in phantom limb pain sometimes linked to?
Any pain existing pre amputation ie. acute injury or chronic pain
What are the 2 theories behind the aetiology of phantom limb pain?
1) Cortical reorganisation
2) Central sensitisation
Explain the cortical reorganisation theory behind phantom limb pain?
Get cortical reorganisation in the body maps of the thalamus and cortex - eg map becomes distorted so that a stroke on the face is felt on the missing limb
Explain the central sensitisation theory behind phantom limb pain?
Get permanent changes in the synaptic structure of the dorsal grey horn
Get a reduction of inhibitory processes and sprouting of a delta terminals into lamina 1 and 2 - ie neurones from the amputated limb die but this theory suggests you may have sprouting of these neurones which reconnects them to the brain
Why can the interpretation of pain vary greatly from the reality of a painful stimulus - ie. severely wounded soldiers can carry on and labour pains vanish after childbirth?
Because the perception of pain is subject to central modulation
Opiate receptors exist in the brain, opiate drugs can be used but the body also produces opiate like chemicals what are there function?
Opiate chemicals produced in the body control pain, immune responses and other body functions
What are endogenous opioids called, what type of substance are they?
Endorphins - they are peptides
Name 5 endogenous opioids?
1) Met-encephalin
2) Leu - encephalin
3) a, b, gamma endorphin
4) Dynorphin
5) Peptides E and F
Endogenous opioids are synthesised from what 3 distinct opioid propeptides?
1) Proenkephalin
2) Proopioidmelanocortin
3) Prodynorphin
What 2 receptors do cannabinoids act on?
CB1 and CB2 receptors
What is the effect of cannabinoids on the body?
Inhibits behavioural responses to acute noxious stimuli, limits hyperalgesia and neuropathic pain
How do higher brain centers influence pain perception?
Descending endogenous analgesic pathways from peri-aqueductal grey and reticular formation decrease transmitter release from primary afferent terminals by an interaction with opioid receptors
What kind of inhibition do opioids have on primary pain afferent terminals?
Pre-synaptic inhibition
What percentage of the adult population experience chronic pain?
9%
What is the difference in outcome of nociceptive stimuli in physiological pain compared to pathological pain?
In physiological pain nociceptive stimuli lead to acute pain which is protective In pathological (chronic) pain nociceptive stimuli causes hyperalgesia (increased pain sensation) and ongoing pain
What is the difference in outcome of innocuous stimulation in physiological pain compared to pathological pain?
Physiological pain - non painful sensations
Pathological pain - Allodynia (touch evoked pain)
What is hyperalgesia?
When tissue that has already been damaged or inflamed is unusually sensitive, can be:
1) A reduced threshold for pain
2) An increased intensity of painful stimuli
3) Spontaneous pain
What is the gate theory of pain and what does it explain?
Have primary afferents coming in but they don’t synapse immediately
Have interneurons which are inhibitory acting on the synapses between primary afferents and secondary neurones
These interneurons can be activated by non-noxious stimuli - explains why pain can be reduced by stimulating mechanoreceptors - eg. rubbing your knee after falling over
The gate theory of pain explains how what machine used to reduce pain works?
TENS machine
