This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
Stimulation and Inhibition are not due to any particular stimulating or inhibitory centres; they are merely dependent on the wave-length of nervous stimuli or the rapidity of transmission, and on the lengths of the paths along which they have to travel. Any nerve-cell may therefore exercise an inhibitory or stimulating action on any other nerve-cell, and the nature of this action will be merely a question of the length and arrangement of its connections, and the rapidity with which stimuli travel along them.
If the hypothesis be true we ought to be able to convert inhibition into stimulation, and vice versa, by either quickening or slowing the transmission of stimuli. We can quicken transmission by heat, and we can render it slower by cold.
On this hypothesis we would expect to find that either excessive quickening or excessive slowing of the passage of stimuli between the cells of the nerve-centres might cause a number of stimuli which would ordinarily interfere to coincide and produce convulsions. This is what actually does occur, for extreme heat and extreme cold both cause convulsions. But it is unsafe to lay too much stress upon this point, as the cause of convulsion may be very complex. We find, however, as we should expect on this hypothesis, that the inhibitory action of the vagus is destroyed by cold.1
There are certain phenomena connected with the action of drugs on the spinal cord which are almost inexplicable on the ordinary hypothesis, but which are readily explained on that Of interference. Thus belladonna when given to frogs causes gradually increasing weakness of respiration and movement, until at length voluntary and respiratory movements are entirely abolished, and the afferent and efferent nerves are greatly weakened. Later still, both afferent and efferent nerves are completely paralysed, and the only sign of vitality is an occasional and hardly perceptible beat of the heart, and retention of irritability in the striated muscles. The animal appears to be dead, and was believed to be dead, until Fraser made the observation that if allowed to remain in this condition for four or five days, the apparent death passed away and was succeeded by a state of spinal excitement. The fore-arms pass from a state of complete flaccidity to one of rigid tonic contraction. The respiratory movements reappeared; the cardiac action became stronger, and the posterior extremities extended. In this condition a touch upon the skin caused violent tetanus, usually opisthotonic, lasting from two to ten seconds, and succeeded by a series of clonic spasms. A little later still the convulsions change their character and become emprosthotonic. These symptoms are due to the action of the poison upon the spinal cord itself, for they continue independently in the parts connected with each segment of the cord when it has been divided.
1 Horwath, Pflilger's Archiv, 1876, xii. p. 278.
This action may be imitated by a combination of a drug which will paralyse the motor nerves with one which will excite the spinal cord. Fraser concludes that the effects of large doses of atropine just described are due to a combined stimulant action of this substance on the cord, and a paralysing one on the motor nerves. The stimulant action on the cord is masked by the paralysis of the motor nerves, and only appears after the paralysis has passed off. He thinks that the difference in the relations of these effects to each other, which are seen in different species of animals, may be explained by this combination acting on special varieties of organisation. In support of his views he administered to frogs a mixture of strychnine which stimulates the spinal cord, and of methyl-strychnine, which paralyses the motor nerves, and found that the mixture produced symptoms similar to those of atropine. Notwithstanding this apparently convincing proof, it would appear that the paralysis in the frog is due to the action of the atropine on the spinal cord, and not to a paralysing effect on the motor nerves. For Ringer and Murrell have found that when the ends of the motor nerves in one leg are protected from the action of the poison by ligature of the artery there is no difference between it and the unpoisoned leg, while if Fraser's ideas were correct the unpoisoned leg ought to be in a state of violent spasm.
A condition very nearly similar to that caused by atropine is produced by morphine. When this substance is given to a frog, its effects are exactly similar to those produced by the successive removal of the different parts of the nervous system from above downwards. Goltz has shown that when the cerebral lobes are removed from the frog it loses the power of voluntary motion, and sits still; when the optic lobes are removed it will spring when stimulated, but loses the power of directing its movements. When the cerebellum is removed, it loses the power of springing at all; and when the spinal cord is destroyed, reflex action is abolished.
Now these are exactly the effects produced by morphine, the frog poisoned by it first losing voluntary motion, next the power of directing its movements, next the power of springing at all, and lastly, reflex action. But after reflex action is destroyed by morphine, and the frog is apparently dead, a very remarkable condition appears, the general flaccidity passes away, and is succeeded by a stage of excitement, a slight touch causing violent convulsions just as if the animal had been poisoned by strychnine.1
The action of morphine here appears to be clearly that of destroying the function of the nerve-centres from above downwards, causing paralysis first of the cerebral lobes, next of the optic lobes, next of the cerebellum, and next of the cord. But it seems probable that the paralysis of the cord first observed is only apparent and not real; and in order to explain it on the ordinary hypothesis we must assume that during it the inhibitory centres in the cord are intensely excited, so as to prevent any motor action, that afterwards they become completely paralysed, and thus we get convulsions occurring from slight stimuli.