Pain and Nociception Flashcards
What is pain?
An unpleasant sensory and emotional experience associated with actual or potential tissue damage and described in terms of such damage
Which nerve fibres mediate nociceptive pain?
Adelta and C fibres
Adelta = sharp stabbing pain
C = dull, aching pain
What is the adaptive/biologically useful role of noiceptive pain?
Protective function
When is noiceptive pain elicited?
When intense/noxious stimuli threaten to damage normal tissue
What is nociceptive pain characterised by?
High threshold and limited duration
What are the 2 types of clinical pain?
Acute and chronic clinical pain
Describe acute clinical pain
Acute clinical pain results from soft tissue injury or inflammation. Serves as a protective function
Describe chronic clinical pain
A sustained sensory abnormality > 3 months. Result of an ongoing peripheral pathology e.g. chronic inflammation, peripheral nerve injury. Pain is maladaptive -> offers no survival advantage . Pain induction might be spontaneous or evoked
What is tactile allodynia?
Painful sensation to a previously innocuous stimulus
How many pairs of nerves are in the cervical segment of the spinal cord?
8
How many pairs of nerves are in the thoracic segment of the spinal cord?
12
How many pairs of nerves are in the lumbar segment of the spinal cord?
5
How many pairs of nerves are in the sacral segment of the spinal cord?
5
How many pairs of nerves are in the coccygeal segment of the spinal cord?
1
How many spinal cord segments are there?
31
The location of pain can be useful in differential diagnosis. Why is the location of pain potentially misleading?
- Referred pain
- This is pain felt in one part of the body but the pathology is elsewhere
- Pain tends to be referred to sites of common embryological origin
- Referral due to a convergence of inputs in the CNS
Where does pain tend to refer from?
From an internal organ to a superficial area e.g. skin
Tends to be referred to sites of common embryological origin
Provide an example of referred pain
Ischaemic pain e.g. angina, can be referred to the left arm
What are pain receptor endings?
Free nerve endings
What type of fibres are cutaneous and subcutaneous mechanoreceptors?
ABeta afferents
Nociceptor endings display sensitisation. What does this mean?
Nerve fibres have a set period of time that they are able to generate action potentials. Adapts to stimulus despite continuous tissue damage
What is the pathway for nociception for the body (not the face)?
Spinothalamic pathway
What is the pathway for nociception for the face?
Anterior (ventral) trigeminothalamic tract
Describe the spinothalamic tract
- Primary sensory neuron projects from the periphery to the dorsal horn of the spinal cord
- 2nd order projection neuron projects from dorsal horn to the antero-lateral funiculus, then continues on to the spinal lemniscus in the thalamus.
- 3rd order projection neuron: from thalamus to sensory cortex
Describe the anterior (ventral) trigeminothalamic tract
- Pain receptors: free nerve endings extend into the dentine
- Free nerve fibres project via C or Adelta fibres in trigeminal nerve to spinal nucleus in the spinal cord
- Synapse onto 2nd order projection neurons - send axons to opposite side of the body up through brainstem to thalamus
- 3rd order projection neurons: from thalamus to the sensory cortex
Briefly describe the spinothalamic tract
- primary sensory neuron from the periphery projects to dorsal horn of the spinal cord (Adelta and C fibres)
- 2nd order projection neuron projects from the dorsal horn to the antero-lateral funiculus and continues up the spinal cord, through the brainstem and synapses in the spinal lemniscus in the thalamus
- 3rd order projection neuron projects from thalamus to sensory cortex
Briefly describe the anterior (ventral) trigeminothalamic tract
- primary sensory neuron from the tooth (free nerve fibres that project into dentine) - Adelta and C fibres
- Synapses with 2nd order projection neuron in the spinal nucleus of the spinal cord
- 2nd order projection neuron crosses over to opposite side of the body and continues up through the brainstem and to the thalamus where it synapses with 3rd order projection neuron
- 3rd order projection neuron from thalamus to sensory cortex
At which level do axons cross over to the opposite side of the body in the spinothalamic tract?
Level of the spinal cord (2nd projection neuron projects from the dorsal horn to the opposite side of the spinal cord (the antero-lateral funiculus) and continues up to the spinal lemniscus in the thalamus where it synapses with 3rd order projection neuron
At which level do axons cross over to the opposite side of the body in the anterior (ventral) trigeminothalamic tract?
At the level of the spinal nucleus of the spinal cord
What does the SCN9A gene encode?
The alpha-subunit of the voltage-gated Na+ channel, Nav1.7
Where is the voltage-gated Na+ channel (Nav1.7) strongly expressed?
In nociceptive afferents (receptor endings)
What does a mutation in the SCN9A gene (SCN9-/-) cause?
Loss of Nav1.7 function (voltage-gated Na+ channel) -> inability to experience pain, but sensory and motor tests normal
What are some of the psychological factors that can affect pain perception?
Sex, age, cognitive level, previous pains, family, culture
What are some of the situational factors that can affect pain perception?
Expectation, control, relevance
What are some of the emotional factors that can affect pain perception?
Fear, anger, frustration
What is the gate control theory of pain?
- In-built systems help us control our perception of pain
- e.g. rubbing hand following a slap, decreases pain
- Noxious stimulus activates Adelta/C fibres -> projects along spinothalamic pathway
- Side branch at the dorsal horn of spinal cord: rubbing hand activates the inhibitory interneuron population. Blocks activity of secondary neurons. Information not conveyed by spinothalamic pathway. Blocks pain perception
Explain how to gate control theory of pain can block pain perception
- Noxious stimulus activates Adelta/C fibres -> projects along spinothalamic pathway
- Side branch at dorsal horn of spinal cord: rubbing hand will active inhibitory interneuron population. Blocks activity of secondary neuron. Information not conveyed spinothalamic pathway => blocks pain perception
What is descending modulation of nociceptive input?
- ‘Supraspinal loop’ contributes to the modulation of nociceptive afferent input
- Serotonergic and noradrenergic descending projections from the periaquaductal grey (PAG) and medullary raphe nuclei
- Direct inhibition of projection neurons and/or activation of enkephalin-containing interneurons reduces activity in nociceptive circuits
Where do descending serotonergic and adrenergic neurons project from?
From the periaqueduct grey (PAG) and medullary raphe nuclei
What do serotonergic and noradrenergic descending projections from the PAG and medullary raphe nuclei do in the ‘supraspinal loop’?
- Direct inhibition of projection neurons and/or activation of enkephalin-containing interneurons
- This reduces activity in nocieptive circuits
What is the supraspinal loop also known as?
Descending modulation of nociceptive input
What does the supraspinal loop do?
Contributes to the modulation of nociceptive afferent input
What are the 5 cardinal signs of inflammation?
Rubor (redness), tumor (swelling), calor (heat), dolor (pain), loss of function
What is the white reaction?
- Red line where the stimulus has occurred = red reaction
- Whitening of the skin = wheal (this region is oedematous/swollen). Surrounds the red line
- Flare = reddened area surrounding the wheal
Describe the triple response
- K+ and prostaglandins released by tissue damage
- Activators for receptive endings in noiceptive terminals
- Plasma: releases bradykinins
- Platelets: release serotonin
- Spinothalamic pathway is activated
- Receptive endings in skin also release CRGP and substance P
- CGRP and Substance P activate local mast cells
- Local mast cells degranulate and release histamine
- Histamine acts on receptive nerve endings to reinforce that there is trauma within that region
- CGRP also causes dilation of blood vessels (flare region)
- Substance P causes extravasation and oedema (wheal region)
Briefly describe the triple response
- Red reaction (where the stimulus has been applied e.g. scratch on skin)
- Wheal = whitening of skin, surrounds red line. Area is oedematous/swollen.
- Flare = reddened area surrounding the wheal
- Tissue damage released K+ and prostaglandins, plasma releases bradykinin, and platelets release 5-HT
- Receptive endings in skin released CGRP and Sub P
- CGRP and Sub P activate local mast cells, which release histamine. Histamine acts on receptive endings, reinforces that there is trauma in that region.
- CGRP causes dilation of blood vessels (flare region)
- Sub P causes plasma extravasation and oedema (wheal region)
What is dermatographia?
Exaggerated triple response
How do local anaesthetics work?
- Block Na+ channels -> block generation at the source
- Can also get anaesthetics that interfere with other components of the spinothalamic pathway
