The general action of a drug on sensory nerves is much more difficult to ascertain with precision than its effect upon motor nerves, because the evidences of sensation we have in the lower animals are cries, and movements either of the limbs or involuntary muscles, such as the iris, arteries, or bladder, which ensue on irritation of sensory nerves.

In the production of these movements or cries, many structures are concerned, viz. sensory nerves, nerve-centres, spinal or cerebral motor nerves, and muscles. It is comparatively easy to ascertain the local action of the drug upon sensory nerves, for in this case these other structures are not affected. By applying the substance to one part of the body, either by painting it upon, or injecting it under, the skin, and then comparing the effect of stimulation produced by pinching or by the application of heat or electricity upon that and other parts of the surface, we can see whether or not the sensibility of the sensory nerves has been affected by the drug.

But when the drug is absorbed into the circulation, it may affect all the other structures already mentioned, as well as the sensory nerves, and thus it may be impossible to decide with certainty whether these nerves are affected or not. But even here definite results are sometimes obtainable, as in the case of curare. The method of experimenting is that of local protection, arresting the circulation in one leg of a frog by applying a ligature to the sciatic artery. The animal is then poisoned with curare, or any drug the action of which is to be ascertained. The poison is carried by the circulation to all other parts of the body excepting the ligatured leg.

In the case of curare the motor nerves are paralysed by the drug, and it would be impossible to ascertain whether irritation of the sensory nerve produced any effect at all, were it not that the ligatured limb, retaining its irritability, serves as an index to the condition of the nerve-centres. At first it is found that pinching the poisoned foot will cause movements in the non-poisoned leg. This shows that the sensory nerves retain their irritability and transmit the stimulation up to the spinal cord, whence it is reflected down the motor nerves to the non-poisoned foot.

As the poisoning becomes deeper, however, pinching the poisoned leg produces much less effect.

This might be due to paralysis of the spinal cord, but it is shown that this is not the case by pinching the ligatured leg just above and below the ligature.

It is found that a pinch just below the ligature causes marked reaction, while a pinch just above has little or no effect.

In this experiment all the structures concerned in the movement have been alike subjected to the action of curare with the exception of the ends of the sensory nerves below the ligature. It is thus evident that the diminished reaction from pinching above the ligature is due to paralysis of the ends of the sensory nerve, in the part of the body to which the poison has had access, and which is shaded dark in the engraving (Fig. 54).

In the experiment just mentioned, the second of the two methods already described (p. 147) in the reference to motor nerves is employed, and the action of the drug on the ends of sensory nerves is ascertained by preventing the poison from reaching them; but the first method may also be employed and the action ascertained by applying the poison to the ends of the sensory nerves, while the nerve-trunks and nerve-centres are protected from its action. Thus, in the experiments of Liegeois and Hottot upon the action of aconitine on the sensory nerves, they ligatured the vein and injected the poison into the artery of a frog's leg; the poison was thus carried to the ends of the sensory nerves in the skin, while it was prevented from reaching the nerve-centres. In this way they found that irritation of the poisoned skin ceased to produce any reflex action, while stimulation of the trunk of the nerve distributed to that leg still caused well-marked reflex action. Normally the terminations of a sensory nerve in the skin are much more sensitive than the trunk of the nerve; and this experiment therefore proves that aconitine paralyses the ends of the sensory nerves.

The local action of drugs on the sensory nerves in man is ascertained by producing, when applied locally, either diminution in pain which may be present at the time, or insensibility, which is usually ascertained by the sesthesiometer. This instrument is simply a pair of compasses with blunt points and a scale by which the distance of the points from one another can be read off.

When the sensation is acute, the points are distinctly felt as two, even when they are but slightly separated from one another; but when the sensation is blunt, they are felt as one when they are at a considerable distance apart.

In frogs the local action on sensation is ascertained by dipping one leg for some time in the solution to be tested, and then comparing the effect of irritating corresponding points in the two feet or legs by pinching, by the application of acids, or by a faradaic current. In this way it has been ascertained that hydrocyanic acid has a powerful local action in paralysing sensory nerves. Where the drug is very powerful, its action on the nerve-centres might complicate the result, if a sufficient quantity should be absorbed into the blood. This fallacy may be avoided by arresting the circulation entirely through excision or ligature of the heart.