1. Pain & the Brain A discussion from a system’s viewpoint Or why do we need more than one neuron for perception?

2. The brain from an evolutionary viewpoint Optimized to promote survival Does not reflect reality Subjective senses of different species cannot be reconciled Therefore, we exist in our subjectivity Including science? Physics? Math???

3. Definition of nociception Detection and response to injurious events Sensory modality w all its characteristics

4. Scales of neuroscience Inverse relation between scale & reductionist vs. synthesis approaches Complexity requires approaches that reduce the dimensionality

5. Cajal vs. Golgi Neuron doctrine Cyncitia Hebb: N fire together wire together

6. Various technologies applicable to mapping the brain at different scales

7. Synaptic events

8. Fundamental questions of neuroscience Structure vs. function Action vs. perception/sensation Motor activity is causally complete Perception lacks scientific explanation Zombies

9. Brain cartography Alhazen, Kitab Al Manazir 1083 Descartes 1662

10. Phrenology 1810 Retina 1866 Brodmann 1909 Early 20 th century

12. 1.Scale 2.Segregation 3.Integration 4.Connectivity 5.Functional rules Macaque Vs Hierarchy of Vs fMRI PET Or. Sel. Ocu. Dom.

13. Reductionist examples Properties of individual units can explain the whole

17. Dorsal column pathway & Spinothalamic pathway: There are multiple other ascending nociceptive pathways. Most important is the spinal-brainstem- amygdala-prefrontal projection, which may be important in arousal and emotional responses to pain.

18. Descending modulation: SPA & MIA have a common intrinsic inhibitory circuitry. Opiates found in: PAG NRM LC Sp Cord

19. What do we miss by looking at the unit? Population properties is not apparent from the unit Also, population properties is not a simple addition of the units And, individual properties may even be irrelevant at the group level. We do not need to know the properties of the apple to understand gravity.

20. Receptive field Peripheral Central Fundamental unifying notion that binds concepts regarding electrophysiology of the brain Can be defined at the level of the single neuron or for a brain region. what means primary visual cortex?

21. Henry Head Head, Rivers & Sherren 1905 Section of radial n Top: no T :cotton wool, H, C, Prick Bottom: 1 year later: Red: sense prick, H 2 O 50 & 0 o C No sense, cotton wool, H 2 O 38, 25 o C

22. Median N A-delta M-Noci RF 2X2 mm c.v. 32 m/s C- slowly adapting r 51 g VF D- 100 g VF E- prick F- No R to heat Microneurography:

23. Human thermal pain perception Closely matches the stimulus-response Curve for CMH CMH

24. Similar neurons are found in: Spinal cord Thalamus SI cortex WDR vs. NS cells

25. Convergence Vs. Lateral inhibition

26. Nicolelis et al. Neuron ‘97 Spatiotemporal spread of neuronal activation across many processing levels of the rat trigeminal somatosensory system, following stimulation of a single whisker. SpV spinal nucleus of trigeminal complex. PrV Principal nucleus of trigeminal complex.

27. VPM SI Layer V Receptive fields are spatiotemporal properties of central neurons. Time-dependent single VPM & SI neuron responses to whisker deflections. Ghazanfar & Nicolelis, Cerebral Cortex 01

28. Fanselow et al, PNAS, 01 Whisker twitchingQuiet immobility

30. Pain is a unique sensory modality It is also a complex phenomenon with: 1.Sensory properties – quality, location, intensity 2.Affective properties 3.Attentional properties 4.Motor responses 5.Homeostatic responses Multiple distinct states: Acute – transient (seconds to minutes) Inflammatory – persistent (days to weeks) Neuropathic – chronic – maladaptive (can last a lifetime) Cancer ?? Pain (subjective conscious) and nociception:

31. Human thermal pain perception Closely matches the stimulus-response Curve for CMH CMH LaMotte & Campbell 1978 Suppression based on past history Sensitization

32. Gottschalk A, Smith DS. Am Fam Physician. 2001;1979-84. Injury Injury Pain Intensity 10 8 6 4 2 0 Stimulus Intensity Normal Pain Response Allodynia Hyperalgesia Hyperalgesia – heightened sense of pain to noxious stimuli Allodynia – pain resulting from normally painless stimuli

33. Thalamic dynamics of pain

35. Pairwise analysis network

36. Spatiotemporal dynamics

38. C.I. Moore et al. 00 3T fMRI, 3 Hz VF or Tennis B Sq Modality segregated multiple somatotopic maps

39. Areas showing pain intensity dependence are contralateral. Areas pain intensity independent are right lateralized. Coghill et al. 01

40. Pathways and cortical regions involved in acute pain perception:

41. Synchronization across brain areas

44. 

45. Listening to music Network hubsActivity

51. Conclusions

52. Mourning women, 500 BC, Archeology museum