From: Bear MF, Connors BW, Paradiso MA (2001) Neuroscience: Exploring the Brain. 2 nd Edn.

3. “Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Pain is always subjective. Each individual learns the application of the word through experience related to injury in early life. It is unquestionably a sensation in a part of the body but it is also always unpleasant and therefore also an emotional experience.” (Definition of pain; International Association for the Study of Pain, 1979)

4. “A Canadian woman born with an indifference to painful stimuli had no other sensory deficits & was quite intelligent. Despite early training to avoid damaging situations, she developed progressive degeneration of her joints & spinal vertebrae, leading to skeletal deformation, degeneration, infection, &, finally, death at age 28.Apparently, low levels of nociceptive activity are important during everyday tasks to tell us when a particular movement or prolonged posture is putting too much strain on our body. Even during sleep, nociception may be the prod that makes us toss & turn enough to prevent bedsores or skeletal strain.People with a congenital absence of pain reveal that pain is a separate sensation, not simply an excess of the other sensations. Such people usually have a normal ability to perceive other somatic sensory stimuli.” From: Bear MF, Connors BW, Paradiso MA (2001) Neuroscience: Exploring the Brain. 2nd Edn. Lippincott, Williams & Wilkins, Baltimore.

5. “The index case for the present study was a 10-year-old child, well known to the medical service after regularly performing ‘street theatre’. He placed knives through his arms & walked on burning coals, but experienced no pain. He died before being seen on his 14th birthday, after jumping off a house roof… All 6 affected individuals had never felt any pain, at any time, in any part of their body… All had injuries to their lips (some requiring later plastic surgery) &/or tongue (with loss of the distal third in 2 cases), caused by biting themselves in the first 4 yr of life. All had frequent bruises & cuts, & most had suffered fractures or osteomyelitis, which were only diagnosed in retrospect because of painless limping or lack of use of a limb. The children were considered of normal intelligence by their parents & teachers, & by the caring physicians…”From: Cox JJ et al. (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature 444, 894-898.

6. Pain is a distinct modality • Pain is sensed by specific receptors (nociceptors) projecting through distinct pathways • Nociceptors respond to noxious (damaging or potentially damaging) stimuli • The main submodalities of pain are “fast” and “slow” pain

10. [Pain] [Touch]

11. From: Payne R, Allen RR (1998) Pain. Scientific American Medicine

12. Excitatory synapses drive the postsynaptic neuron’s membrane potential towards threshold, increasing the probability of an action potential

13. Inhibitory synapses drive the postsynaptic neuron’s membrane potential away from threshold, decreasing the probability that an action potential will be generated.

15. LIMBIC SYSTEM Learning & Memory Emotion

16. Painful stimuli evoke protective reflexes as well as sensations & emotions

19. Pain can be controlled at several levels

20. TERMS • Analgesia: loss of sensibility to pain (e.g. Aspirin is an analgesic) • Anaesthesia: total loss of sensation (e.g. Barbital is an anaesthetic)

21. ANAESTHESIA • Local anaesthesia: produced by injection of an anaesthetic drug in a limited area (e.g.injection of novocaine near a branch of the trigeminal nerve for tooth extraction) • General anaesthesia: loss of consciousness in addition to loss of sensation (e.g. inhalation of fluothane for abdominal surgery)

26. Pain aspirin TRAUMA mechanical thermal chemical Prostaglandins leukotrienes substance P NOCICEPTOR SENSITISATION hyperalgesia K+, 5-HT, histamine, bradykinin NOCICEPTOR STIMULATION A-delta fibres, small, myelinated, 5-30 m/sec, sharp, pricking pain C fibres, small, unmyelinated, 0.5-2 m/sec, dull, aching pain xylocaine DORSAL HORN Acupuncture, cutaneous stimulation opioids morphine spinothalamic ? HYPOTHALAMUS autonomic responses THALAMUS SOMATOSENSORY CORTEX location, intensity general anaesthetics LIMBIC SYSTEM emotional aspects ASSOCIATION CORTEX pain perception IC Bruce, 2000

27. From: Payne R, Allen RR (1998) Pain. Scientific American Medicine

28. Endogenous pain control via opioids

30. DISSOCIATIVE ANAESTHETICS • Central analgesia with an anaesthetic-like state of altered consciousness • Produced by compounds like phencyclidine (“Angel Dust”) and ketamine

31. REFERRED PAIN • Pain perceived as coming from a source remote from its actual origin • Characteristic of pain in the viscera • e.g. heart pain “referred” to the left arm in angina pectoris • pain in the diaphragm “referred” to above the clavicle in pleurisy

33. From: Payne R, Allen RR (1998) Pain. Scientific American Medicine