Principles of Neuroscience Lecture 25 Pain Flashcards
Define nociception
Nociception is the activation of nociceptor primary afferents
Describe how nociception is distinct from mechanoreception
These are two distinct pathways, with different sensory neurons: mechanoreceptors and nociceptors
It is possible to stimulate nociception w/o somatosensory on eg. Heat radiating from a light bulb
Define pain
Pain is the conscious experience of unpleasant somaesthetic to the body
Define Hyperalgesia
This is heightened sensitivity to noxious stimuli
What is the function of the primary afferents in nociception?
These detect and transduced noxious stimuli and carry this information to the CNS
What are the different types of nociceptor primary afferents?
Compare and contrast
A-delta fibres: very lightly myelinated, slow conducting, detect pain and temperature
“First pain”: high intensity, short lived
C fibres: unmyelinated, even more slowly conducting, detect pain, temperature and itch
“Second pain”: lower intensity, longer lived
If the A-delta nociceptor is lesioned, is it possible to still get a pain response ?
Yes. The two nociceptor types can function independently
Describe how capsaicin elicits a nociception response
- Capsaicin is taken into the mouth or onto skin
- Since it is lipid soluble it moves across the plasma membrane
- It binds to the TRP ion channel, on the inside of the cell
- The TRP channel opens, and K+ and Na+ move into the cell: depolarisation
- The nociceptor undergoes and action potential
What other molecules act on TRP channels?
What is the response?
Heat and H+ can open TRP channels, causing nociceptors to fire
Describe the pathway from the Primary afferent nociceptor to the brain
- Primary afferent nociceptor
- Cell body in Dorsal root ganglion
- Enters the dorsal part spinal cord
- Lissauer’s tract - Synapses and decussates
- Moves up the spinal cord in the Anterolateral system
- Ventral posterior nucleus of the thalamus
7a. Somatosensory cortex
7b. Anterior cingulate cortex
7c. Insular cortex
7d. Amygdala and hypothalamus
What is the name of the tract in the dorsal horn of the spinal cord where stuff goes on with the nociceptor afferents?
Describe what goes on here
Pain afferents enter and move up and down several segments in this tract before penetrating the grey matter, synapsing with the second order neuron, decussating and ascending in the anterolateral system
To which area of the brain does Pain information first go?
- The ventral posterior nucleus of the thalamus
2. Midline thalamic nuclei
Describe the interactions with interneurons in the dorsal horn
There are several laminae
Here, the primary afferent synapse with interneurons which connect to second order neurons, and there is interaction between mechanoreceptors and nociceptors
Describe the features of Brown-Séquard Syndrome
One half (eg. LHS) of the spinal cord is lesioned LHS below lesion: reduced somato-sensation, pain and temperature sensation is intact RHS below lesion: reduced pain and temperature sensation, somato-sensation is intact
What are the two pathways that pain information takes once it gets to the brain?
Sensory- discriminative
Affective-motivational
What is the Sensory-Discriminative pathway of pain?
VMPN -> S1 and S2
This localises the pain to the area which the stimulus is originating
What is the Affective-Motivational pathway?
This is the perception of pain
A-L system -> hypothalamus and amygdala
Insular cortex, anterior Cingulate cortex
What is the function of the Cingulate cortex?
This is where the experience of pain is detected
What is the function of the Insular cortex?
This is the localisation of pain within the body
This area has an unconscious map of the body
How does pain information from the face reach the brain?
The afferent form the trigeminal tract, which enter the brain stem at the pons, descends to the medulla, synapses and decussates, then ascends to the thalamus
Describe how the inflammatory response interacts with nociception
- Tissue damage
- Inflammatory cells release ATP, H+, prostaglandins, histamine, Bradykinins
- These molecules act on primary afferent nociceptors, causing them to fire.
- Nociceptors also release Substance P into the damaged tissue, stimulating Mast cells and neutrophils to release more inflammatory substance. POSITIVE FEEDBACK LOOP
Describe Primary and Secondary Hyperalgesia
Primary: surrounding nerves in the surrounding inflamed tissue are activated –> increased sensitivity
Secondary: nerves in the surrounding, uninflamed tissue are activated –> sensitivity
Which molecules are released by Mast cells and Neutrophils that act on primary nociceptor afferents?
H+, ATP, Bradykinin, Prostoglandins, Histamine
Describe the phenomenon of Phantom Limbs
This is when there is perception of pain in limbs that are no longer there.
Give a few examples of how there can be altered perceptions of pain
- Child birth: it is an immensely painful experience, but women ‘forget’ this experience afterwards
- Soldiers who lose limbs on the battlefield continue to fight
- Intense fear has the ability to dampen down the nociceptor sensory system
What are the mechanisms of altering pain perception?
- Mechanoreceptor inhibition of nociceptors
2. Descending inhibition of nociceptors
Describe how mechanoreception and nociception can be antagonistic
Mechanoreceptors activate inhibitory interneurons, thus inhibiting the second order nociceptor neurons
Describe how descending systems can alter the perception of pain
There are nuclei in the brain that have descending projections to the spinal cord. These neurons activate the inhibitory interneurons, thus inhibiting nociception
S1 -> amygdala, hypothalamus -> Raphe nucleus -> dorsal horn of spinal cord -> A-L system
How is visceral pain perceived (give the pathway from organ to brain)? How does this relate to the anterolateral system?
Visceral pain is completely separate from the A-L system, it is a separate pathway
- Eg. Gastrointestinal tract distended
- Primary afferent
- Cell body in dorsal root ganglion
- Spinal cord, synapse, ipsilateral projection up the dorsal column
- VPMN of thalamus
- Insular cortex
What is the pain stimulus that is detected as pain in the viscera?
Distention of viscera
No temperature detection
What is the evidence for visceral pain pathway being located in the dorsal column?
In monkeys, there was an experiment performed where the dorsal column was lesioned
Then, there was a noxious distention stimulus delivered to the colon and rectum. In the lesioned monkeys, there was no activity in the thalamus and insular cortex. In the normal monkeys, there was.
What is one way that we can give relief of visceral pain?
Punctate midline myelotomy
Why might visceral pain often be mis located?
There is no interaction of the visceral pain information with the somato sensory cortex
Can pain be described as a pathway?
No, that is too over simplified
Pain is more of a network
a. Interaction between nociception and mechanoreception
b. descending information from brain
Which region of the thalamus does information from the enteroceptors go?
VPMN
