Recently, because of discrepancies between results obtained with intracellular recording techniques in vivo, and whole-cell patch-clamp techniques in culture and slices, and because of reports of success using whole-cell techniques in vivo in other systems (bat inferior colliculus125 and rat cortex126), it was determined that whole- cell recording techniques could also be applied to the nociceptive systems of the spinal cord of the rat in vivo.79 All the cell types that have previously been observed in the superficial dorsal horn by extracellular recording techniques may be found with whole-cell patch techniques in the superficial dorsal horn of the rat.79
The advantages of this technique have been outlined above in conjunction with intracellular recording techniques in vivo. This technique has added advantages:
1. Better control over the electrical properties of the recorded neuron because of the very low resistance of the patch pipette and the resultant very high resolution of the recording of electrical events within the neuron.
2. Small cells can be sampled even in the difficult to stabilize rat spinal cord, presumably because the whole-cell technique is more robust than sharp electrode intracellular recording techniques.
3. Cells can easily be labeled by placing .05% biocytin in the patch pipette.
4. Intracellular medium can be controlled by placing drugs or ions in the patch pipette which has easy access to the inside of the patched neuron.
5. The extracellular medium can also be controlled to a certain degree by superfusion with artificial cerebrospinal fluid, much like superfusion of slices in a chamber. Superfusion is actually very effective because the cells of the superficial dorsal horn are very close to the surface (30 to 200 àm deep).
Some other potential advantages of this technique include on-cell patching in vivo that would allow the observation of single channels in their native milieu, and the ability to apply drugs to the inside of a single, physiologically identified cell to determine the effects on nociceptive throughput. The major disadvantages of this technique are
1. Difficulties in proper stabilization of experimental animals in vivo.
2. Interactions of the necessary anesthetics with the nociceptive functions of the neurons.
3. Difficulties in obtaining adequate seals because of movement, and cover- ing astrocytes (in adult rats, up to 80% of blind seals form on astrocytes, not neurons, after which the pipette must be discarded).
4. Possible alteration of the response of the recorded neuron because of dialysis of factors not present within the patch pipette.
5. Not knowing the nature of the recorded neuron until after the experiment, since cells cannot be visualized until then (although, the projection targets of the recorded neuron may be determined by antidromic stimulation).
In practice, it has been much more difficult to achieve whole-cell recordings in in vivo than in in vitro slices, which in turn is more difficult than achieving whole- cell recordings in culture. The in vivo whole-cell technique is not the best method for obtaining large samples of patch-clamped neurons to study. Recently, Yoshimura’s lab has published a study on substantia gelatinosa neurons recorded in vivo in the whole-cell mode, in which they failed to find nociceptive thermal inputs that excited cells.127 While we have found substantia gelatinosa neurons with noxious thermal inputs in the rat,79 it is possible that sampling problems can selectively limit the population of neurons recorded with this technique.
In summary, each experimental electrophysiological technique described here has advantages and disadvantages. Which approach is best depends on the question being asked. Furthermore, given that there are disadvantages to each approach that may limit the interpretation of results obtained, it is useful whenever possible to employ several different approaches to the characterization of ion channels involved in the control of afferent excitability and subsequent CNS processing of stimuli perceived to be painful.
ACKNOWLEDGEMENTS
This work was supported by the Whitehall Foundation (I.S.), NINDS grants NS36929 (M.S.G), NS39420 and NS16433 (A.R.L).
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