1. 746 Human Brain Pain

2. Pain : Aim nperception nperipheral responses u role of NSAIDs e.g. aspirin nspinal modulation u gate control u peptidergic modulation nCNS

3. Perception npain u human description u 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 ". nphantom pain u amputees nWhy do we need pain?

4. Nocioception nnoxious stimuli u animal models ? nassociated with parts of CNS

5. Peripheral responses nSpecialised receptors nPain is not just neurons firing more often nAdequate stimuli nRole of u aspirin u Paracetamol u Ibuprofen

6. Pain is… nnot just neurons firing more often

7. Specialised receptors nHeinbecker 1933 A-  u faster than 2.5m/s u high threshold mechanoreceptors - 20 cm -2 u sharp pain nC u slower than 1m/s u polymodal F heat - pressure - noxious chemicals

8. Pain is… nouch nache

9. Adequate stimuli ntemperature nC fibers sensitive to very low concentrations of u histamine 10 -8 M, ACh 10 -8 M u Prostaglandins 10 -10 M u no one chemical ?? nreleased by tissue damage

10. Capsaicin ntransient effect of chillies - capsaicin nLoss of nocioceptive response in new born rats with capsaicin

11. Capsaicin nActive ingredient of chillies nActivates TRPV1 channels

12. Role of aspirin naspirin blocks Cyclooxygenase u = COX u = PGH synthase ncovalent modification to ser - 530 u http://cti.itc.virginia.edu/~cmg/Demo/pdb/cycox/cy cox.html arachidonic acid COX  prostaglandin PGG2 COX  prostaglandin PGH2

13. Other NSAIDs n n on- s teroidal a nti- i nflammatory d rugs nIbuprofen u COX competitive inhibitor nParacetamol u = Acetaminophen u = N-acetyl-para-aminophenol u COX-3 inhibitor

14. Summary so far nPain perceived A -  and C fibres nresponse to pain blocked by NSAIDs u prostaglandin synthesis nNext: Spinal cord...

15. Spinal Cord DRG ventral root dorsal root dorsal horn

16. Gate control hypothesis nMelzack & Wall (1965) nin the spinal cord the pain pathway is modulated

17. Gate control hypothesis

18. Neuromatrix nMelzack & Wall revised their theory to elaborate on the spinal cord system as neuromatrix

19. Evidence ? nanatomical npharmacological nphysiological nanecdotal

20. SG substantia gelatinosa nlayered nmap of skin

21. Anatomy - cont

22. Enkaphalins in SG ndrawing of nocioceptive cell in SG nenkephalin immunoreactive nenkephalin receptors mu delta kappa

23. endogenous opioids nTyr-Gly-Gly-Phe-Met nTyr-Gly-Gly-Phe-Leu

24. Morphine nderived from opium naction as analgesic in spinal cord nusually codeine OCh 3

25. Substance P n11 amino acid peptide nArg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met nFound in CNS and dorsal horn of spinal cord nExample of a tachykinin

26. SP as a transmitter nmain excitatory transmitter is glutamate ncapsaicin blocks C fibers selectively

27. tactile stimuli nMummy rub it better ? u lateral inhibition ? nTENS

28. Modulation in SG

29. Summary so far: nspinal modulation ngate control or neuromatrix ntactile stimuli nTENS nSG nSP nopioids nnext: CNS

30. Gate & CNS nnoradrenaline nserotonin nenkephalin nstress

31. CNS nCNS itself not sensitive to pain u meninges are - local anaesthetic nregional specialisation nleucotomy u removal of frontal lobes / thalamus to remove pain perception PET scan shows blood flow

32. Summary npain as human response nperipheral control by NSAIDs nspinal control - peptide neurotransmitters ncontrol by brain