Transcript Systematic Neurophysiology

The
Puzzle of
Pain
The Reverend Dr. David CM Taylor
http://pcwww.liv.ac.uk/~dcmt/painpuz.ppt
Synopsis
• We will have a brief overview of different types of
pain, including what is meant by first and second
pain, and the neural pathways involved.
• We will discuss the recent understanding of the
genetics of pain, and synaesthesia.
• We will then discuss control of pain, through the Gate
Control hypothesis, and descending control
generally.
• This will lead us to consider the differences between
pre- and post-synaptic inhibition.
“The Puzzle of Pain”
We believe in electricity
•
•
There was a long fight between those who believed in chemicals and
those who believed in electricity
Both were right but, to send the information along the nerve
Na+ channels open, and let +ve ions into the cell, which is then “excited”
K+ channels open and let +ve ions out of the cell, which is then “inhibited”
Ca2+ channels “control” the duration of excitement.
•
•
Think of a Mexican wave
And chemicals are released at the end.
“Tell me where it hurts…”
Image of pain pathways removed for copyright reasons.
Spinothalamic tract and spinoreticular/intralaminar pathways
There is more than one ....
First
Second
pin prick, heat
tissue damage
Pathway
A mechanical
mechanical/heat
spinothalamic
Distribution
Body Surface
C and A
polymodal
spinoreticular
intralaminar
thalamic
Most tissues
Reflex
Phasic
contraction
Adequate
stimulus
Sensory unit
Tonic contraction
Gate Control Theory
Melzack and Wall in 1968
rubbing injured region decreases pain sensation
detail wrong but useful
Descending
control
Touch fibre
_ +
+
Gate
cell
Pain fibre
_
Transmission
c ell
_
+
_
Descending Inhibition
Touch
cortico-thalamic pathways
why we don’t feel clothes
Pain
battle and sporting injuries, ecstasy
children, animals, elderly/suffering
There is a lot to understand
•
Particularly interesting, though, are the people who can’t feel pain, and
the people who feel too much
•
Some of the people with chronic pain have a problem with a potassium
channel subunit which is the product of a single gene KCNS1
•
Some people with low sensitivity to pain have a problem with a gene
which codes for part of the Calcium channel α2δ3
Synaesthesia
Interestingly most people
with an abnormality in
α2δ3 also experience
synaesthesia
Problem?
•
The genes were identified by groups who started with the fly hot-plate
test
•
And then went on to test the results in animals
•
Before checking on people.
Descending control of pain
microinjection of opiates into discrete regions of the CNS (PAG,limbic
system, SG) produces analgesia
Microstimulation there also produces analgesia
Opioid peptides are present there
Electrical stimulation of the PAG or NRM produces analgesia
“Tell me where it hurts…”
Image of pain pathways removed for copyright reasons.
Spinothalamic tract and spinoreticular/intralaminar pathways
Proposed mechanism
limbic system
periaqueductal grey
nucleus raphe magnus
interneurones in lamina II of spinal cord
Presynaptic hypothesis
5HT
from brain
enkephalin
substance P fibre
pioneered by Leslie Iversen
to brain
How might control work?
Electrical (“Sherringtonian or…”)
Shorter action potentials,
Altered levels of “second messengers”
less Ca2+, less transmitter release, less activity
Chemical
Alter gene expression
Change level or type of
transmitter released or
Receptors on post synaptic cells
Post-synaptic hypothesis
from brain
A fibre touch
c-fibre “pain”
to brain
This is the currently accepted “gate control” theory