3. OK, so previous slide shows that morphine in peripherally analgesic doses does not affect pain produced by aversive stimulation of midbrain spino- reticular pain system Naysayers say: Maybe stimulation too sharp- edged and high frequency, i.e., unnatural…… so 1). we created soft stimulus in next slide, 2) we tried 200 vs 5 Hz.

7. Naysayers still complain: “ Yeah but stimulating central pain path is like nothing natural such as foot shock. In foot shock you activate a fraction of pain paths, in brain you hit all the concentrated pain neurons simultaneously …” OK, so we stimulated on either side of the “pain gate.” Fibers are equally concentrated, but differently located in cord or trigeminal system.

12. All over the brain…. …Same thing!

14. Enkephalin endogenous opiates do the same thing……..

16. What follows is the documented anatomy of possible analgesia systems

18. Do PAG and PGC work together? Behavioral study first…. But we really needed single cell recording…later. Here are behavioral data:

21. Complication: Fields’ work In RM, 2 kinds of neurons: 1) ON CELLS—turned on by pain and off by opiates. (Top & Bottom in next slide) 2)OFF CELLS—turned off by pain and on by opiates (2 middles in next slide)

24. OK, so they work together, i.e., PAG and PGC summate on common RM Cells. And the effect of 2 injections conjointly, whether in off-cells or in on cells is greater than effect of either single injection alone. But are PAG and PGC both necessary? If you remove one, will the other work?