Transcript 746 Human Brain

746 Human Brain
Pain
Pain : Aim
 perception
 peripheral responses
 role
of NSAIDs e.g. aspirin
 spinal modulation
 gate
control
 peptidergic modulation
 CNS
Perception
 pain
 human
description
 International Association for the Study of
Pain: "Pain is an unpleasant sensory and
emotional experience associated with actual or
potential tissue damage, or described in terms of
such damage".
 phantom pain
 amputees
 Why do we need pain?
Nocioception
 noxious stimuli
 animal
models ?
 associated with parts of CNS
Peripheral responses
 Specialised receptors
 Pain is not just neurons firing more often
 Adequate stimuli
 Role of
 aspirin
 Paracetamol
 Ibuprofen
Pain is…
 not just
neurons
firing more
often
Specialised receptors
 Heinbecker 1933
 A-d
 faster
than 2.5m/s
 high threshold mechanoreceptors - 20 cm-2
 sharp pain
C
 slower
than 1m/s
 polymodal
 heat
- pressure - noxious chemicals
Pain is…
 ouch
 ache
Adequate stimuli
 temperature
 C fibers sensitive to very low concentrations
of
 histamine
10-8M, ACh 10-8M
 Prostaglandins 10-10 M
 no one chemical ??
 released by tissue damage
Capsaicin
 transient effect of chillies - capsaicin
 Loss of nocioceptive response in new born
rats with capsaicin
Capsaicin
 Active ingredient of chillies
 Activates TRPV1 channels
Role of aspirin
arachidonic acid
COX 
prostaglandin PGG2
COX 
prostaglandin PGH2
 aspirin blocks Cyclooxygenase
=
COX
 = PGH synthase
 covalent modification to ser - 530

http://cti.itc.virginia.edu/~cmg/Demo/pdb/cycox/cy
cox.html
Other NSAIDs
 non-steroidal anti-inflammatory drugs
 Ibuprofen
 COX
competitive inhibitor
 Paracetamol
=
Acetaminophen
 = N-acetyl-para-aminophenol
 COX-3 inhibitor
Summary so far
 Pain perceived
 A - d and C fibres
 response to pain blocked by NSAIDs
 prostaglandin
synthesis
 Next: Spinal cord...
Spinal Cord
DRG
dorsal
root
ventral
root
dorsal horn
Gate control hypothesis
 Melzack &
Wall (1965)
 in the spinal
cord the pain
pathway is
modulated
Gate control hypothesis
Neuromatrix
 Melzack & Wall revised their theory to
elaborate on the spinal cord system as
neuromatrix
Evidence ?
 anatomical
 pharmacological
 physiological
 anecdotal
SG substantia gelatinosa
 layered
 map of skin
Anatomy - cont
Enkaphalins in SG
 drawing of
nocioceptive cell
in SG
 enkephalin
immunoreactive
 enkephalin
receptors
mu
delta
kappa
endogenous opioids
 Tyr-Gly-Gly-Phe-Met
 Tyr-Gly-Gly-Phe-Leu
Morphine
 derived from opium
 action as analgesic in spinal cord
 usually codeine OCh3
Substance P
 11 amino acid peptide
 Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu
Met
 Found in CNS and dorsal horn of spinal cord
 Example of a tachykinin
SP as a transmitter
 main excitatory transmitter is glutamate
 capsaicin blocks C fibers selectively
tactile stimuli
 Mummy rub it better ?
 lateral
 TENS
inhibition ?
Modulation in SG
Summary so far:
 spinal modulation
 gate control or neuromatrix
 tactile stimuli
 TENS
 SG
 SP
 opioids
 next: CNS
Gate &
CNS
 noradrenaline
 serotonin
 enkephalin
 stress
CNS
 CNS itself not
sensitive to pain
 meninges
are - local
anaesthetic
 regional specialisation
 leucotomy
 removal
of frontal
lobes / thalamus to
remove pain
perception
PET scan shows
blood flow
Summary
 pain as human response
 peripheral control by NSAIDs
 spinal control - peptide neurotransmitters
 control by brain