746 Human Brain Pain. Pain : Aim nperception nperipheral responses u role of NSAIDs e.g. aspirin nspinal modulation u gate control u peptidergic modulation.

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-

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

aspirin blocks Cyclooxygenase = COX = PGH synthase

covalent modification to ser - 530 http://cti.itc.virginia.edu/~cmg/Demo/pdb/cycox/

cycox.html

arachidonic acid COX

prostaglandin PGG2COX

prostaglandin PGH2

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 - and C fibres response to pain blocked by NSAIDs

prostaglandin synthesis

Next: Spinal cord...

Spinal Cord

DRG

ventralroot

dorsalroot

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 inhibition ? TENS

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