Lecture 26 - Pain & Pleasure I Flashcards
(30 cards)
State the IASP definition of Pain
“Unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”
List some features of the pain experience
How is pain experienced?
How can this experience be affected?
How is pain expressed?
- Always subjective (no objective measure)
- Extent of the tissue damage can be a poor indicator of the pain being experienced
- The relationship between tissue damage and pain is variable
- Pain is only experienced when nociceptive signals form the tissue reach the conscious brain
- Pany cognitive factors can thus affect the pain experience
- Culture
- Beliefs
- Past experience
- The situation
- Pany cognitive factors can thus affect the pain experience
- Pain is expressed in behaviour
- This is how one expresses pain to others
Describe the ‘pain pathway’
Describe endogenous inhibition of this pathway
Summarise exogneous inhibition of various points along this pathway
- Free nociceptor nerve endings in the tissue
- TRPV1
- Capsaicin
- TRPV3
- Mustard
- TRPV1
- Action potential transmission along axon
- Voltage gated Na+ channels
- Cell body in dorsal root ganglion
- Synapse on neuron in dorsal horn of spinal cord
- Glutamate onto NMDA & AMPA receptors
- 2° neuron ascends several spinal segments
- Decussation
- Ascends up lateral spinothalamic tract
- Synapse on thalamus
- Third order projections to:
- Post central gyrus
- Peri-aquaductal grey (PAD)
Descending pain control pathway:
- Projections from PAD release inhibitory neurotransmitters onto first synapse in the Rexed lamina
- Noradrenaline (NA)
- Serotonin (5-HT)
- These projections are stimulated by endogenous opioids
- “Walking wounded”
Gate theory of analgesia
- Mechanoreceptors inhibit the first synapse in the spinal cord by releasing inhibitory neurotransmitters
- GABA
- Glycine
Exogenous inhibition:
- Exogenous opioids activate the PAD
- TCA (tricyclic antidepressants), such as Amitryptyline inhibit uptake of NA and 5-HT at first synapse
- Deep brain stimulation activates the PAD
- NSAIDs inhibit the generation of prostaglandins
- Local anaesthetic inhibits voltage gated Na channels, thus inhibiting neural transmission of nociceptors
- Ketamine inhibits NMDA receptors in first synapse
Describe how cognition can affect perception of pain
Pain is processed by certain areas in the brain:
- Amygdala etc.
that contribute psychological components to the experience of pain
Describe pain as a sensory experience
Once nociceptor signals reach the thalamus, there are thrid order projections to the post-central gyrus (ie somatosensory cortex)
Describe the sensory pathway of visceral pain
- Nociceptor free nerve endings in organs
- Cell body in dorsal root ganglion
- First synapse in spinal cord
- Ascends up a few segments
- Decussation
- Ascends in dorsal columns
- Like somatosensory neurons
- As opposed to nocicpetors from skin which ascend in lateral spinothalamic tracts
- Synapse on thalamus
- Thrid order projections to Insular cortex
List the various aspects of sensation in the skin
- Hair follicles
– Aβ fibres –
- Meissner corpuscle
- Dynamic deformation (slipping)
- Pacinian corpuscle
- Vibration
- Merkel cell
- Indepntation depth
- Ruffini corpuscle
- Stretch
– **C-fibres **–
- Free nerve endings, no specialised terminals
- Touch
- Pleasant touch
- Low threshold
- Sensory + pleasure
- Nociception
- When intensity of stimulus is noxious
– Aδ fibres –
- Nociception
- Sensory + affective
- Noxious pain / itch
List tissues in which nociceptors are found
- Skin
- Joints
- Within the joint, the nociceptors has simple nerve terminals, like in the skin
- Mechanosensors in the joint have more specialised terminals, as in the skin
Compare sensory transmission to noxious and mechanical stimuli
Mechanical stimulus:
- eg touching an object
- Aα fibres fire at a constant rate while the object it being touch
- Stop firing once the stimulus is removed
Noxious stimulus
- eg flame on finger
- Aδ fibre fires at an increasing rate while the stimulus is present
- Firing continues once the stimulus is removed, tissue damage
Describe detection of pain by eating chillies
- Chili contains capsaicin
- Capsaicin activates TRPV1 channels on the free nerve endings of nociceptors (Aδ fibres)
- Aδ fibre fires
Outline the functional nociceptor classes
- Thermal
- Aδ fibres
-
TRPV1 channel (and others)
- Sensitive to heat
-
TRPM8 channel (and others)
- Sensitive to cold
- Activated by Menthol
- Mechanical
- Aδ fibres
- Polymodal
- C fibres
- Slient
Outline the various channels present on nociceptors
- Peripheral terminal
-
TRPs
- Transient receptor potential channels
- Sensitive to pressure, heat, cold, molecules etc.
- Na+ and Cl- channels once activated: initiate action potentials
-
TRPs
- Peripheral axon
- **Nav: **voltage gated sodium channels
- **Kv: **voltage gated potassium channels
- **HCN: **hyperpolarisation activated cation channels
- Central axon and synapses
- **Cav2.2: **voltage gated calcium channel
- Cav3.2
- Control the exocytosis of synaptic vesicles containing neurotransmitters, thus controlling the synapse
Which type of fibres are nociceptors?
Give features of each
Describe nerve propagation in each
Aδ fibres
- Lightly myelinated
- Pain, temperature
- Sharp, acute pain
- *
C fibres
- Unmyelinated
- Pain, temperature, itch
- Slow, burning pain
- *
What is the name for non-hairy skin?
Glaborous skin
Where do second order pain neurons ascend in the spinal cord?
In the spinothalamic tract
Describe spinal reflexes
What has this got to do with pain?
Nociception without pain
- Stimulus: stretch on tibialis
- Activation of nociceptive fibres
- Synapse on interneurons
- Activation of motor neurons for tibialis
- Contraction of tibialis
Describe referred pain
- Activation of nociceptors in viscus
- Neural transmission to spinal cord and up to brain
- Thalamus
- Projections to post-central gyrus
- Perception of pain in the skin supplied by the same nerve root
What is hyperalgesia?
Outline the mechanism
Decreased pain threshold following injurous stimulus
Mechanism:
- Peripheral sensitisation
- Tissue damage
- Release of prostaglandins, bradykinin etc.
- Diffuse into surrounding, undamaged tissue aswell
- These molecules bind to GPCRs
- Phosphorylation of TRPs
- Decreased threshold of TRPs in peripheral terminals in damaged tissues and surrounding, non-damaged tissue
- Central sensitisation
- Upregulation of NMDA and AMPA
- Nociceptors in far reaching non-damaged tissue now sensitised (lower threshold)
Differentiate between primary and secondary allodynia and hyperalgesia
What brings about each?
Primary allodynia/hyperalgesia
- Brought about by peripheral sensitisation
- ie increased TRP channel sensitivity
- Lower intensity noxious stimuli will elicit pain
Secondary allodynia/hyperalgesia
- Brought about by central sensitisation
- Innocuous stimuli will elicit pain
When does secondary hyperalgesia occur?
Sustained exposure to noxious stimulus
Where is the somatosensory cortex?
Post-central gyrus
Describe pain in phantom limbs
What has fMRI told us about this?
Pain experienced in a limb that has been amputated
fMRI:
- Areas of the brain that map the amputated limb are active whilst the pain is being experienced in the phantom limb
- Areas that map the ‘phantom limb’ are re-mapped and expanded in response to the loss of sensory input from the limb
Outline how attention and mood affect experience of pain
- Attention
- Intensity predominantly attenuated when distracted from pain
- Unpleasantness reduced to a lesser degree
- Mood
- Predominantly affects the affective component of pain
- Unpleasantness diminished when in good mood
- Also intensity, to a more marginal extent
Which molecules can activate TRPV1 channels?
What happens after activation?
- Capsaicin
Molecules released by damaged tissues:
- H+
- Lipids
After activation:
- Conformational change in the receptor
- Na+ and Ca2+ ions move through the channel into the cell
