8. Pain Flashcards
Pain is an unpleasant s____ and e____ experience associated with a____ or p____ tissue damage and d____ in terms of such damage
sensory, emotional, actual, potential, described
Pain is important because…
1. it promotes the a____ of situations which may d____ b____ f____
2. it promotes r____ b____ that either enhances r____ following injury or m____ behaviour so that further injury or death become less likely
- avoidance, decrease biological fitness
- resting behaviour, recovery, modifies
Pain is detected by activating s____ r____ and n____
sensory receptors, nociceptors
Nociceptors are specialised s____ n____ specific to p____. They have f____ nerve e____ and their synapse is in the s____ c____ to a____ neurons to the b____
specialised neurons, pain
free, endings
spinal cord, ascending, brain
Nociceptors are p____, this means they respond to m____ s____
polymodal, multiple stimuli
When tissue is damaged, nociceptors are a____, sending s____ to the s____ c____ and then to the b____
activated, signals, spinal cord, brain
Free nerve endings in nociceptors contain receptors sensitive to noxious stimuli:
1. I____ p____ s____
2. S____
3. P____
- Intense pressure stretching
- Striking
- Pinching
Reflex action:
1. N____ detect painful stimuli
2. Send signal to s____ c____
3. A____ neuron synapse to i____ in s____ c____
4. Send signal via e____ neuron (m____ neuron) to the m____
5. M____ c____ and body part w____
- Nociceptors
- spinal cord
- Afferent, interneuron, spinal cord
- efferent, motor, muscle
- Muscle contracts, withdrawn
(Primary afferent) Að fibres are lightly m____ and have a medium d____. They provide the f____ pain - fast l____ of painful stimulus
myelinated, diameter
first, localisation
(Primary afferent) C fibres are u____ and have a small d____. They provide the s____ pain - a c____ d____ a____ which is poorly l____.
unmyelinated, diameter
second, continuing dull ache, localised
A⍺ and Aβ fibres (normal proprioceptors) are m____ and have a large d____
myelinated, diameter
The first path of pain to the brain is to the s____ cortex via the t____. It e____ the s____ components:
1. S____ d____
2. Tell you “w____” it hurts
somatosensory cortex, thalamus
encodes, sensory
1. sensory discrimination
2. where
The second pain path into the brain is to the ‘e____’ cortex (i____ and c____) via the t____. It e____ the e____ components:
1. U____
2. N____ a____
emotional, insula, cingulate, thalamus
encodes, emotional
1. unpleasantness
2. negative affect
Pain is an a____ signal that something is w____
alerting, wrong
P____ s____ is a pain sensitisation process. It is an i_____ response in and around injured tissue. P____ nerve endings (n____) become more r____ to stimuli, lowering the t____ for pain perception. It involves:
1. H____ = n____ stimuli produce e____ pain sensation
2. A____ = non-n____ stimuli produce pain sensation
Peripheral sensitisation
inflammatory
Peripheral (nociceptors)
responsive, threshold
1. Hyperalgesia, noxious, exaggerated
2. Allodynia, noxious
C____ s____ is a pain sensitisation process. It involves n____ changes in the central nervous system. Neurons become more e____ and respond to stimuli that would normally not t____ a pain response. P____ pain, n____ i____ or i____ can lead to central sensitisation.
Central sensitisation
Neuroplastic
excitable, trigger
Persistent, nerve injury, inflammation
I____, t____ damage and exposure to i____ can trigger peripheral sensitisation.
Inflammation, tissue, irritants
In tissue damage, a bunch of c____ are released as part of the i____ r____.
There is a release of A____ and H+ which directly activates and/or modulates i____ c____ in nociceptor terminals.
N____ (substance P and CGRP) are released from nocireceptor neurons and trigger:
1. V____
2. P____ e____
3. Activation of M____ cells and n____
- chemicals, inflammatory response
ATP, ion channels
Neuropeptides - Vasodilation
- Plasma extravasation (leakage of proteins and fluid from capillaries)
- Mast, neutrophils
The “inflammatory soup”
1. H____ - causes v____ and increased p____, leading to swelling and redness
2. N____ G____ F____
3. S____
4. P____ - cleave extracellular peptide to b____
5. C____ e____ - convert arachidonic acid (l____) to p____
6. N____ - substance P and CGRP
7. C____
- Histamine (mast cells) - causes vasodilation (widening of blood vessels) and increased permeability, leading to swelling and redness
- Nerve Growth Factor (mast cells)
- Serotonin (platelets)
- Proteases cleave extracellular peptide to bradykinin (A peptide that sensitizes nociceptors, making them more responsive to pain stimuli.)
- COX enzymes (cyclo-oxygenase) convert arachidonic acid (lipid) to prostaglandin (contribute to inflammation, pain, and fever)
- Neurotransmitters:Substance P and CGRP(released by nociceptors)
- Cytokines (IL-1β, TNF-α)
Modulation of the nociceptor activation…
Components of the inflammatory soup, Bradykinin, NGF and Prostaglandin feedback back to their own metabotropic receptors on the nociceptor neurons :
1. VR1 receptor is p____ and t____ changes so opens at l____ t____
2. A s____ n____ s____ Na+ channel is p____ so threshold v____ for f____ is decreased, making the nociceptor more e____
3. Nociceptors become h____ to stimulation - peripheral sensitisation
- phosphorylated, threshold, lower temperatures
- sensory nerve specific, phosphorylated, voltage, firing, excitable
- hypersensitive
Central sensitization “wind up pain”:
1. Nociceptor a____ release g____ and substance P in spinal cord which activates the s____ neurons
2. R____ firing results in n____ changes in the spinal cord, s____ the synapse so less stimulation will create a larger s____
3. NMDA receptor activation leads to influx of __
4. Substance P activates NK1 receptor (metabotropic) which leads to:
a) p____ of NMDA and AMPA receptors
b) receptors become more r____ to g____
c) neurons more e____ (long term potentiation)
5. Substance P d____ to other synapses, so “wind up” can spread causing a g____ s____ to painful stimuli
- afferents, flutamate, spinothalamic
- Repetitive, neuroplastic, strengthening, signal
- Ca2+
a) phosphorylation
b) responsive, glutamate
c) excitable - diffuses, generalised sensitisation
The Gate Control Theory of Pain, proposed by Ronald Melzack and Patrick Wall in 1965,suggests that a “gate” in the spinal cord can m____ or b____ pain signals from reaching the brain, influenced by both large and small n____ f____ and brain processes
modulate, block, nerve fibres
The Gate Control Theory states that stimulation of A⍺ or Aβ fibres in the v____ of an i____ activates i____ in d____ horn which inhibits s____ neuron from firing. Competition between e____ (from nociceptor) and i____ (from priorioceptors). This can p____ the pain signals getting to the brain.
vicinity, injury, interneuron, dorsal, spinothalamic, excitation, inhibition. prevent
When in a v____ r____ environment whilst having dressings changed, burn patients reported a reduction in pain ratings by __-__%. They also reported a reduction in time spent t____ about pain, pain i____ and how u____ they found the pain.
There was also reduced activity in p____ p____ areas of the brain when treatment in presence of virtual reality. This included the s____ cortex, a____ c____, i____ and t____.
virtual reality, 30-50%
thinking, intensity, unpleasant
pain processing
somatosensory cortex, anterior cingulate, ínsula, thalamus
Stress induced analgesia is an a____ response to d____-r____ pain. The central mechanism triggers d____ r____ of pain circuitry to i____ pain signals arriving in the brain. One mechanism involves the release of e____ o____.
adaptive down-regulate
descending regulation, inhibit, endogenous opioids (naloxone challenge (opioid antagonist) blocks the analgesic effect)
Descending Inhibitory Pain Modulation is a mechanism where the brain sends signals down to the s____ c____ to r____ or b____ pain signals. It involves brain regions like the p____ g____ and r____ v____ m____. It activates the e____ o____ system, which releases e____ and other o____ that bind to receptors in the spinal cord, reducing pain transmission.
spinal cord, reduce, block
periaqueductal gray, rostral ventromedial medulla
endogenous opioid, endorphins, opioids
Descending Inhibitory Pain Modulation:
1. O____ inhibit i____ neurons in the p____ g____, allowing e____
2. D____ PAG neurons fire and activate s____ neurons from the r____ n____
3. S____ neurons excite enkephalinergic neurons in the s____ c____
4. Enkephalin release acts on o____ receptors on the nociceptor t____ in the d____ horn
5. This inhibits firing of s____ neurons through pre- and post-synaptic effects
- Opioids, inhibitory, periaqueductal gray, excitation
- Disinhibited, serotonergic, raphe nuclei
- Serotonergic, spinal cord
- opioid, terminal, dorsal
- spinothalamic
Capsaicin (the active ingredient in chilli) is an a____ of TRP channels and can be used to d____ pain receptors.
agonist, desensitise
Opiates can be used to treat pain. They make work through:
1. A____ of the e____ o____ system
2. Trap into bodies own system of pain r____
They have multiple sites of action:
1. P____
2. S____ c____
3. C____
- agonists, endogenous opioid
- regulation
- Peripherally
- spinal cord
- centrally
Methods of tapping into the endogenous opioid system:
1. E____ s____ of PAG
2. A____
3. P____
4. Non-o____ mechanisms
- electrical stimulation
- acupuncture
- placebo
- opioid
Chronic or persistent pain is pain that lasts longer than __ weeks, or beyond the n____ h____ time
12 weeks, natural healing
Possible mechanisms leading to chronic pain:
1. Peripherally:
- S____ of peripheral neurons
- Increased activity of d____ a____ and s____
2. Centrally:
- h____ of central neurons
- R____ of s____ c____ in spinal cord
- D____ - removal of t____ d____ inhibitory control
- sensitisation
- damaged axons, sprouting
- hyperexcitability
- reorganisation, synaptic connectivity
- disinhibition, tonic descending
Biological factors of individual differences in pain sensitivity and response:
1. D____ with genetic c____
2. Genetic v____ in c____ of system
3. I____ with other systems
- Disorders with genetic component
- Genetic variability in components of system
- Interactions with other systems
Factors in sex differences in pain perception:
Biological factors =
1. G____ differences
2. Sex h____
3. Brain i____
Psychosocial factors =
1. N____ emotion
2. C____ strategies
3. S____ influences
- genetic
- hormones
- imaging
- negative
- coping
- social
There is a differential sensitivity to m____ in males and females - females tend to be …. sensitive
morphine, more
