But there were naysayers:

• Maybe with high frequency (300cps), square pulse (instant rise) ESB you are giving un-natural activation of CNS pathways.

• Maybe by activating entire central pathways, you are also doing something that doesn’t happen in nature. Sooooooo……

We did an expewriment:

• Much slower soft starting stimulation at low frequency

• &• We stimulated centrally the same

density of fibers in and outside the descending inhibition.

This was M & L’s very important theory of descending inhibition…(rather than suppression of higher pathways.

• Morphine had no effect on the aversive reaction threshold for the “Miss” at left (101% baseline). But it elevated the aversive reaction threshold of the “hit” to 320% baseline.

Is there a summation of effects…

• ….from 2 or more interacting sites?

• First study was behavioral:

But where were the summation(s)?

• This required a study of single neuron responses to see if one lower level could be activated to a greater by two higher places than by either alone.

Studying neurons in NRM presented us with a wrinkle:

• Fields & colleagues at UCSF found that there were 2 kinds of cells in NRM, On Cells and Off Cells.

• On cells turned on by pain, off by opiates.• Off cells ere the other way around: turned

off by pain, on by opiates.• Thus cells had to be On/Off classified

before studying summation effects. Classification done with tail flick in lightly anaesthetized rats, ala Fields.

So, we showed that different brainstem sites interacted at RM…• But was one site (e.g., PAG)

necessary for the other site (e.g., PGC) to function? This suggested a reversible lesion experiment:

Naturally naysayers said “nay”…

• “You are comparing a double injection (PGC-M + PAG-T) with a single one (PGC-M). “

• OK so we did the appropriate comparison to get the thing published:

So of course next, we had to see what the lesions did to on and off

cell responses.

Moral of the story:

• If you stay away from complex higher cognitive functions and study something simple (like sensory responsiveness, e.g., pain) then you can learn a lot with lesions & ESB