Pain Flashcards
How can pain be defined?
‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage’
- a combination of sensory and affective components
- pain is always subjective
What is nociception?
The sensory component of pain alone
What is the pathway by which pain is perceived?
- Free nerve endings in skin, muscle, viscera
- Activated by intense (noxious) stimuli
- Generates AP
- Stimulus intensity encoded through firing rate
- Propagated centrally
What are the 2 types of nociceptors?
What are they activated by?
What pain fibres are they associated with?
Mechanical
- activated by strong shearing force in skin
- e.g cut, strong blow
- A delta fibres
Polymodal
- respond to many stimuli e.g. sharp blow, damaging heat, chemicals released by damaged tissue (e.g. K+, H+, histamine, prostaglandins, bradykinin)
- C fibres
Are primary sensory neurones inhibitory or excitatory?
All excitatory
Synapse in dorsal horn
Describe structural and functional differences between C and Adelta fibres
What kind of pain are they responsible for?
Adelta fibres
- myelinated
- fast transmission/conduction velocity
- responsible for first, sharp pain, quickly after stimulus
C fibres
- unmyelinated
- slower tranmission/conduction velocity
- responsible for the second, dull, burning pain, present longer after stimulus
How are nociceptive inputs organised in the dorsal horn?
laminar and somatotopic organisation
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Where do C fibres terminated in the dorsal horn of the spinal cord?
substantia gelatinosa
- What makes up the vast majority of dorsal horn neurones?
- What is their function?
- Are they inhibitory or excitatory?
- What must the pain signal do, in order to be sent to the brain?
- local interneurones
- modulate activity of projection neurones
- majority are inhibitory, spontaneously active, or stimulated by primary afferent input
- pain signal must overcome inhibition to be sent to brain
Describe the gate control theory of pain in terms of the neurones involved in the following:
- Gate closed to non-noxious input
- Arrival of noxious stimulus, opening of gate
Gate closed to non-noxious input
- Abeta mechanoreceptor (non-nonxious) fibres are primary afferent neurones and are therefore excitatory
- Inhibitory interneurones in the dorsal horn inhibit the output neurones and prevent pain signals to the brain
- The Abeta fibres are excitatory and synapse with these interneurones so that no pain signals are sent if the mechanoreceptors are stimulated
Gate open, noxious stimulus
- Now there is excitatory input from Adelta/C fibres directly onto the output neurone
- But also onto another inhibitory interneurone that inhibits the other inhibitory neurone (connected to mechanoreceptors) and therefore disinhibits the output neurone and so pain signals can ascend to the brain
What is the clinical significance of the gate control theory
- increased non-noxious afferent input to the spinal cord for analgesic effect
- TENS, electrical signal through skin activated Abeta fibres but not Adelta/C.
- Abeta are big and quite easy to excite
- Abeta input is capable of closing the gate at the spinal level
What are the ascending pathway involved in the reception of pain and what are their roles?
Ascending spinothalamic pathway - C fibres mostly
- synapses in the thalamus
- perceived at a subcortical level
- localised at the cortical level
- limbic system important in feeding in affective component (emotion)
What are the descending pathways involved?
What is their role?
- feedback control
- cortical input can trigger descending fibres which could reduce the pain
- brain stem nuclei (rich in opioids), released of 5-HT from RV medulla, noradrenaline from PAG, ekephalin from locus coereleus
- closing the spinal gate
- Intrinsic Analgesia System
What is the idea of facilitated pain?
What are the two mechanisms that will do this?
normal physiological pain is directly proportional to afferent input duration and intensity
- however in chronic/persistent pain state, sensitivity to pain can be increased
Two mechanisms
1. peripheral sensitisation
2. central sensitisation
What is hyperalgesia?
enhanced painful response to a normally painful stimulus
–> more pain
What is allodynia?
painful response to a normally non-painful stimulus
What is the pain threshold?
The stimulus intensity at which an innocuous stimulus because noxious
Describe the changes in pain sensation induced by injury
Injury shift the pain sensation curve to the left
Results in allodynia and hyperalgesia
Pain threshold also shifted down
Describe the mechanism of peripheral sensitisation
- noxious stimulation activates nociceptor directly and causes release of various factors in damaged skin/underlying tissue
- antidromic action potential propagation (NT release at receptor) can occur along the primary afferent fibre branches that innervate injured tissue
- this stimulates substance P and CGRP realise from peripheral nerve ending that acts on the vacularture to cause plasma extravasation and immune cell migration into tissue
- Immune cells release pro-inflammatory substances that act on nociceptors to lower threshold for AP generation
- lower threshold = sensitisation
- antidromic AP propagation along fibre branches that innervate inured AND neighbouring uninjured tissue. Result in sensitisation of neurones that also innervate the neighbouring uninjured tissue.
- This depends on the overall of sensory territories - contributes to sensory hyperalgesia
What is primary hyperalgesia?
What is secondary hyperalgesia?
Primary hyperalgesia = increase pain sensitivity that occurs in the damaged tissue
- peripheral sensitisation promotes central sensitisation
Secondary hyperalgesia = increased pain sensitivity sudan from the site of injury (surrounding tissues)
Describe the mechanism of central sensitisation and secondary hyperalgeis
- mechanism in the spinal dorsal horn
- high frequency afferent input (possibly as a result of peripheral sensitisation) invades presynaptic terminal
- stimulates substance P release (high frequency is required, so not involved in acute pain signalling) as well as increasing glutamate release
- combination of substance P –> Nk1 receptor and glutamate –> AMPA receptor
- produces sufficient depolarisation of the post synaptic membrane to relieve voltage-dependent Mg2+ block of NMDA receptor
- glutamate can then bind to the NMDA receptor resulting in Ca2+ entry
- Ca2+ entry activates intracellular mechanisms increasing neurone responsiveness and amplification of rate of action potential efferent firing long ascending nociceptive pathway
