Pain and nociception Flashcards
Pain definition
an unpleasant sensory and emotional experience associated with actual or potential tissue damage
When is acute (nociceptive) pain evoked?
when intense/noxious stimuli threaten to damage tissues - induced sensory reception
What is the adaptive/biological function of acute pain?
protective function
What is the threshold of acute (nociceptive) pain?
high threshold (difficult to recruit nociceptor endings)
What is the duration of acute (nociceptive) pain?
limited duration
Which afferent fibres are associated with acute (nociceptive) pain?
Ad (A delta) and C fibres
Describe the structure of Ad fibres?
thinly myelinated with a small diameter axon (1-5um)
Describe the structure of C fibres
unmyelinated with a very small diameter (0.2-1.5 um)
What sensation is associated with first pain?
sharp, stabbing pain
Which axon does the sharp, stabbing first pain correspond to?
Ad fibres
What is the sensation of the second pain?
dull, aching pain
Which axon fibre is associated with the perception of dull, aching second pain?
C fibres
What type of peripheral endings transduce noxious stimuli?
free nerve endings (unspecialised)
What axons do free nerve endings give rise to?
Ad and C fibre afferents
What stimuli activate Ad fibre nociceptor endings?
noxious mechanical / heat stimulus
What stimuli activate C-fibre nociceptor endings?
polymodal stimuli (e.g. temp, mechanical, itch)
How are nociceptor endings able to respond to different noxious stimuli?
nociceptor endings carry several types of receptor proteins that each respond to different stimuli
Nociceptor endings display sensitisation. What is meant by this?
the more the nociceptor endings are used, the more readily they are recruited (become more sensitive/responsive)
What is the name of the sensory pathway that transmits pain stimuli from the trunk/limbs?
spinothalamic pathway (somatic nociception)
What perceptions are felt as a result of the spinothalamic pathway?
pain, temperature, crude touch
What type of axon fibres can be the primary sensory neuron in the spinothalamic pathway?
Ad or C fibres
Describe the route of the primary sensory neuron in the spinothalamic pathway
the free nerve endings transduce noxious stimuli and the AP travels along Ad / C fibres into the dorsal horn where it synapses with the secondary sensory neuron
What is the name of the defined region of white matter the second order neuron relays information up through the spinal cord?
antero-lateral funiculus
Describe the path of the secondary sensory neuron in the spinothalamic pathway
conducts the impulse from the dorsal horn and crosses the midline to the opposite side of the spinal cord. Transmits information along the antero-lateral funiculus to the brainstem and then to the thalamus where it synapses with neuron 3
What is the spinal lemniscus?
A bundle of axons in the brainstem
How are the neural populations in the spinal lemniscus activated?
by collateral branches of the secondary sensory neuron as it projects information up the brainstem
Where are the neural populations of the spinal lemniscus located?
medulla, pons and midbrain
What is the name of the ascending projection along the spinal cord and brainstem (including antero-lateral funiculus)?
spinothalamic tract
Describe the pathway of the tertiary sensory neuron in the spinothalamic pathway?
Transmits the impulse from the thalamus through the internal capsule to the sensory cortex where the noxious stimulus is perceived as pain
Where are the free nerve endings of nociceptive afferents in a tooth located?
extending into the dentin
Which nerve do nociceptive afferents from a tooth conduct APs along?
trigeminal nerve (CN V)
What is the name of the sensory pathway that transmits nociception from the face?
anterior (ventral) trigeminothalamic pathway
Describe the anterior (ventral) trigeminothalamic pathway
trigeminal afferent transmits AP from nociceptors in the face to the spinal nucleus where it synapses with neuron 2 which crosses the midline and projects up the brainstem to the thalamus. Neuron 3 carries the impulse from the thalamus to the somatosensory cortex.
What are the receptors of pain pathways?
nociceptors (free nerve endings)
Where is the CNS relay cell found in the spinothalamic pathway?
spinal dorsal horn
Where is the CNS relay cell found in the anterior (ventral) trigeminothalamic pathway?
spinal trigeminal nucleus
What are the 2 CNS pain pathways?
spinothalamic pathway (from body) and anterior (ventral) trigeminothalamic pathway (from face/oral cavity)
What areas of the forebrain are activated by pain pathways?
Primary sensory cortex and possibly subcortical areas
What attributes of pain are valuable in making a differential diagnosis?
location, quality (sharp stabbing, dull ache), intensity, frequency/duration, provoking/relieving factors
What is referred pain?
pain perceived in one part of the body when the pathology is elsewhere
Where does pain tend to refer from and to?
from internal organ to a superficial area (e.g. skin) that tends to have a common embryological origin
What tends to be in common with the area affected by referred pain and the area with the pathology?
embryological origin
What surface area is affected with referred pain from the heart?
left chest and arm
What surface area is affected by referred pain from the oesophagus?
left chest
What surface area is affected by referred pain from the stomach?
UL abdominal quadrant
What surface area is affected with referred pain from the liver and gall bladder?
UR abdominal quadrant
What surface area is affected by referred pain from the appendix and small intestine?
umbilical and suprapubic region
What surface area is affected by referred pain from the ureter?
suprapubic region
What factors can affect pain perception?
genetic, molecular, cellular, anatomical, psychological, physiological, social factors
Which gene mutation can cause an inability to experience pain?
SCN9A- mutation
What does SCN9A encode for?
alpha-subunit of voltage-gated Na+ channel (Nav 1.7) expressed in nociceptors
What happens when the SCN9A gene is mutated?
Nav1.7 loses its function so nociceptive afferents cannot be recruited leading to an inability to experience pain despite normal sensory and motor tests
What psychological factors can impact pain perception?
sex, age, cognitive levels, previous pains, family, culture
What situational factors can alter pain perception?
expectation, control, relevance (of pain to situation)
What emotional factors can alter pain perception?
fear, anger, frustration
Example of 2 in built mechanism to help modulate pain
gate control system and supraspinal loop
What action used to dissipate pain is explained by the gate control system?
rubbing the affected area (activating mechanoreceptors)
How does the gate control theory explain pain modulation?
rubbing activates mechanoreceptors of AB fibres. The principle AB fibre projects into the dorsal column medial lemniscal pathway to sense the rubbing stimulus, while the collateral branch terminates in the dorsal horn and activates inhibitory interneurons. iIN inhibit secondary sensory neurons which blocks the transduction along the spinothalamic tract to the sensory cortex so pain perception is dissipated.
Where do the collateral branches divide from the principle secondary sensory neuron in the spinothalamic pathway?
medulla, pons and midbrain
What is the function of the collateral branches of neuron 2 in the spinothalamic pathway?
intrinsic modulation of nociceptive afferent input via the supraspinal loop (send descending impulses back down spinal cord)
Describe the path information is relayed in the supraspinal loop
information is relayed from the PAG in the pons to the medullary raphe nuclei to the dorsal horn of the spinal cord where projection (secondary) neurons are inhibited
What is PAG?
periaqueductal grey (region of the pons)
What type of projections descend from the PAG (pons) and the medullary raphe nuclei?
serotonergic (5HT) and noradrenergic (NA) descending projections (release serotonin and noradrenaline)
What happens when the descending impulses in the supraspinal loop reach the dorsal horn?
inhibit projecting neurons and/or activate enkephalin-containing interneurons which reduces nociceptive circuit activity
What are the key indicators of mild tissue damage?
redness, heat, swelling, pain, loss of function (inflammation)
What reaction and response takes place when we receive mild mechanical trauma?
white reaction and triple response
What are the 3 aspects of the triple response to mechanical trauma?
red reaction is surrounded by wheal (swells and pales) which is surrounded by flare (mottled)
What term is given to using the triple response to write on skin?
dermatographia
What factors are released as a result of mechanical trauma to the skin?
K+, prostaglandins, bradykinin, 5-HT (serotonin)
Where are K+ and bradykinins released from in response to mechanical trauma?
damaged tissue
Where is bradykinin released from in response to mechanical trauma?
from the plasma of ruptured capillaries
Where is 5-HT (serotonin) released from in response to mechanical trauma?
platelets of ruptured capillaries
What is the function of K+, prostaglandins, bradykinin and 5-HT in the triple response?
activate receptive endings of C fibres which transmit APs into the dorsal horn via the spinothalamic pathway leading to pain sensation
What peptides can be released from free nerve endings?
CGRP and Substace P
How are CGRP and Sub P released?
APs in the C fibre can activate other free nerve endings of the axon causing the release of these peptides
What are the actions of CGRP and Sub P?
activate mast cells and affect local capillaries
What effect do CGRP and Sub P have on mast cells?
cause mast cells to degranulate to release histamine
What effect does histamine have on the triple response?
histamine further activates the receptive endings to reinforce pain input along C fibres
What effects does Substance P have on local capillaries?
releases bradykinin which causes plasma extravasation and formation of oedema
What aspect of the triple response is substance P responsible for?
Wheal (pale and swelling around red reaction)
What effect does CGRP have on local capillaries?
vasodilation (more peripheral)
What aspect of the triple response is CGRP responsible for?
flare
What relieving actions can minimise the blood mediated response of the triple response?
apply pressure and cold water to restrict blood supply, anti-histamines to minimise the effects (pain reinforcement) of mast cell degranulation
What intervention modulates activity in ascending sensory pathways for pain (spinothalamic pathway / anterior (ventral) trigeminothalamic pathway)?
local analgesics
How do analgesics modulate pain?
interfere with AP generation or restrict its conduction
