By using the results of experiments in vitro on the effects of procaine on sensory endings for interpreting the effects of procaine in vivo, it has become clear that there is practically no diffusion barrier in the terminal parts of sensory nerve fibres. Nature has thereby exposed the regenerative region of the sensory ending to the influence of substances circulating in the blood stream. The generator region is probably equally exposed but is apparently more resistant to the effects of drugs. The central parts of the sensory fibres are not easily exposed to the drugs because of the protection afforded by the nerve sheath, which is known to act as a strong diffusion barrier. This barrier can be overcome (equilibrium approached) by infusion of drugs.
The effects of all intravenously injected drugs on sensory endings can be explained by their effects on the regenerative region, which has practically the same properties as the rest of the nerve fibre. Since non-medullated fibres are more susceptible to drugs than medullated fibres, it follows that the regenerative regions of the endings of non-medullated fibres must be more susceptible to drugs. This explains why the endings of non-medullated fibres are more readily stimulated by a variety of substances that leave the endings of medullated fibres unaffected.
The effects of local anaesthetics have revealed that only in higher doses, or after longer action, do such drugs act on the generator region, but when this occurs, the regenerative region is already totally blocked. It may be assumed that the same applies to other drugs.