Pain Flashcards
A study showed that short-term pain induced what in the brain in comparison to long-term chronic pain?
Short-term pain induces activation.
Long-term chronic pain induces strong and extended deactivation in the occipital, frontal and temporal lobes.
What does CIP stand for?
Congenital insensitivity to pain.
What are the two causes of CIP?
Mutation in a gene called SCNP9A which regulates the Nav1.7 pathway.
Overproduction of endorphins (body’s internal pain modulating system).
What is hereditary sensory and autonomic neuropathy (HSAN)?
The pain system degenerates over time, leading to loss of pain sensation.
What is pain asymbolia?
Individuals feel pain but are unable to recognise the unpleasant component of the painful stimulus, resulting in little or no defence reaction.
Damage or alterations to which brain areas give rise to pain asymbolia?
Cingulate region.
Frontal cortex.
Define nociception.
The neural processing of damaging substances or stimuli in response to tissue damage.
Name the five phases of nociceptive pain.
Transduction.
Conduction.
Transmission.
Perception of pain.
Modulation.
Why do we need pain?
Pain is our body’s learning system in response to dangerous activities or noxious and harmful substances.
How do thermoreceptors and nociceptors respond differently to a heat stimulus?
Activation of thermoreceptors increase in line with the temperature rise, then become saturated at around 40-42 degrees Celsius.
Nociceptors only become active at around 45 degrees Celsius.
Which nerve fibres drive heat responses below the pain threshold?
Large diameter non-nociceptive fibres.
Which nerves fibres drive pain signals in response to heat?
Smaller diameter less-myelinated fibres.
Define first pain.
Sharp pain.
Define second pain.
Dull ache associated with pain.
Which nerve fibres mediate first pain?
A-delta fibres.
Which nerve fibres mediate second pain?
C-fibres.
Nociceptive receptors are sensitive to which stimuli?
Thermal.
Chemical.
Mechanical.
Which five areas are nociceptive receptors found in?
Hairy skin.
Glabrous skin.
Muscles.
Joints.
Blood vessels.
Intestines.
Why are nociceptive receptors known as free nerve endings?
They lack specialised receptor cells.
How does non-discriminative/poorly localised touch arise?
Stimulation of free nerve endings that act as non-nociceptive, high-threshold mechanoreceptors.
What type of stimulus activates non-nociceptive, high-threshold mechanoreceptors?
Rough stimulus that doesn’t cause tissue damage, e.g. tapping, squeezing, rubbing and stretching of skin.
Describe the activity of non-nociceptive, high-threshold mechanoreceptors.
They have no background activity.
When stimulated, they respond for as long as the stimulus lasts.
What are the two types of non-nociceptive thermoreceptors?
Those activated by heat (35-45 degrees Celsius).
Those activated by cooling (17-35 degrees Celsius).
How do non-nociceptive thermoreceptors respond to changes in ambient temperature?
Graded response.
What happens when non-nociceptive thermoreceptors are repeatedly stimulated?
Become sensitised.
Have a decreased activation threshold.
When stimulus is applied again, a larger response is produced.
Compare and explain the speed of AP conductance in A-delta fibres compared to C-fibres.
A-delta fibres = myelinated, conduct AP rapidly, warning of first (sharp) pain.
C-fibres = unmyelinated, conduct AP slowly and long-lasting, signalling damage (second pain) and warning to protect from further pain.
What is a harmless substance that mimics the action of damaging stimuli and gives rise to pain?
Capsaicin.
Capsaicin is an agonist for which receptor type?
TRP (transient receptor potential) channel.
Which ions are TRP channels permeable to?
Sodium.
Calcium.
There are several types of TRP channels. They mediate responses to which stimuli?
Heat.
Chilli.
Menthol/mint.
Garlic/horseradish.
Pain.
What is a key component in the TRP channel activation pathway?
Calcium ions.
Name the direct and indirect pathways of the anterolateral system (ALS).
Direct = neospinothalamic pathway.
Indirect = palaeospinothalamic pathway.
Which three areas make up the neospinothalamic pathway?
Spinal cord.
Lateral thalamus.
Somatosensory cortices.
Which five areas make up the palaeospinothalamic pathway?
Spinal cord.
Reticular formation.
Medial thalamus.
Cingulate, frontal and limbic cortices.
Which five fibres make up the fibre bundle of the ALS?
Spinothalamic.
Spino-mesencephalic.
Spino-reticular.
Spino-bulbar.
Spino-hypothalamic.
Where do nociceptive fibres originate?
In the periphery.
Where do nociceptive project to and innervate from the periphery?
Into the spinal cord via the dorsal root ganglia (DRG) and innervate the dorsal horn.
What are the six layers of the dorsal horn collectively called?
Rexed laminae.
Which layers of the dorsal horn do A-delta fibres innervate?
R1, 2 and 5.
Which layers of the dorsal horn do C-fibres innervate?
R1 and 2.
Innervation of neurons in R1 and R5 of the dorsal horn project to where?
Thalamus.
Brainstem.
Innervation of neurons in R2 of the dorsal horn project to where?
Spinal interneurons.
Fibres branch up and down in the dorsal horn to form what?
Dorsolateral tract of Lissauer.
What is referred pain?
Pain that is felt in one part of the body but is caused by pain or injury in another part of the body.
What are wide-dynamic range cells?
Second-order neurons in R5 that receive input from non-nociceptive and nociceptive afferents.
What underlies referred pain and how?
Wide-dynamic range cells receive pain messages from the skin and pain messages from within the body (viscera). This leads to sensation of pain in skin areas common to the painful viscera.
How does cauda equina syndrome give rise to referred pain?
The nerve bundle leaving the spinal cord is severely compressed.
A painful numbness is felt in the legs and feet.
Therefore, the pain is felt in a different area compared to the location of the cause.
Do nociceptor afferents project ipsilaterally or contralaterally?
Contralaterally.
Do mechanoreceptor afferents project ipsilaterally or contralaterally?
Ipsilaterally.
How would a unilateral lesion on the left-hand side of the spine affect mechanoreceptive (tactile), temperature and pain sensation below the lesion, and why?
Mechanoreceptive sensation is lost on left-hand side of body.
Information from mechanoreceptors doesn’t decussate, so afferents project ipsilaterally.
Temperature and pain sensation is lost on right-hand side of body.
Information from thermoreceptors and nociceptors decussates, so afferents project contralaterally.
Where do both mechanoreceptive and nociceptive fibres terminate?
Dorsal column.
Name the two distinct aspects of the experience of pain.
Sensory-discriminative.
Affective-motivational.
Which two areas process the sensory-discriminative aspect of the experience of pain?
Ventral posterior nucleus.
Somatosensory cortex.
Which main four areas process the affective-motivational aspect of the experience of pain?
Limbic system, inc. amygdala.
Midline thalamic nuclei.
Anterior cingulate cortex.
Insular cortex.
Why are there two distinct aspects of the experience of pain?
Allows us to use pain signals as part of our emotional perception.
Helps us to pick the best survival response.
e.g. Pain is inflicted –> become angry –> fight back.
Which brain area is involved in the associative component of the pain matrix?
Posterior parietal cortex.
What is the pain matrix?
The brain regions involved in pain processing and pain modulation.
Why is it so difficult to treat neuropathic pain?
Pain is multimodal.
It is experienced as an interconnected, cross-talking complex.
Describe the discriminatory pain pathway.
Pain afferents enter the lumbar spinal cord.
Passes up into anterolateral system.
Ascends up through brainstem regions and into the ventral posterior lateral nucleus of the thalamus.
Information is sent to the sensory cortex.
Describe the discriminatory pain pathway for trigeminal fibres.
Travel down and decussate in the spinal cord.
Ascend up through the same region of the thalamus before entering the sensory cortex.
What is hyperalgesia?
Too much pain/enhanced pain.
How does hyperalgesia occur?
Local tissue damage causes release of inflammatory mediators which enhance the response to pain.
Define sensitisation.
An inflammatory response to tissue damage.
How do peptides contribute to sensitisation/the inflammatory response?
Cause vasodilation of blood vessels and increased inflammation via mast cell release of histamine.
How does the recruitment of external cells contribute to sensitisation/the inflammatory response?
Release interleukins and tumour necrosis factors which interact along with histamine on nociceptive fibres to drive AP firing in the thalamus and/or to switch on TRPV1 channels.
How do prostaglandins contribute to sensitisation/the inflammatory response?
Augment nociceptive receptor excitability via cAMP and phosphorylation of Nav channels to lower AP threshold.
Define non-steroidal anti-inflammatory drugs (NSAIDs), e.g. ibuprofen.
A class of medications used to treat or alleviate pain, fever and other inflammatory processes.
What is allodynia?
When pain responses are sensitised in the brain so all sensory information becomes a painful signal.
How does allodynia occur?
When neurons in the dorsal horn lamina show activity-dependent increased excitability which generalises to their non-nociceptive inputs, and they start to respond to normal mechanoreceptive-type inputs from the skin and the periphery.
Describe the descending pain system.
Descending aminergic inputs activate interneurons containing pain modulators, e.g. endorphins. These impinge and modulate the C-fibres to inhibit C-fibre transmission and decrease the pain sensation.
What is the endogenous system of endorphins, dynorphins and enkephalins?
A group of opioid peptides that are released from pituitary and adrenal glands and bind to opiate receptors on neurons.
Describe the mechanism of action of endorphins.
Act at the dorsal horn.
Cause secretion of enkephalin.
Decreases activation of second order projection neurons.
What mediates the placebo effect?
Descending modulation via opioids.
In one sentence, summarise how pain is modulated.
Pain is centrally (top-down) modulated via aminergic drive of endogenous opioid release.
