Sudden alterations of temperature act as stimuli to nerves. Heat increases their irritability, but its prolonged application diminishes it. Cold in general diminishes the nervous irritability, and may be carried to the point of completely destroying it temporarily.2

2 But at a certain age in freezing the ulnar nerve Mitchell found its irritability notably increased.

Many substances of widely-different chemical constitution, as acids, alkalies, salts, alcohol, chloroform, strychnine, etc., act as stimuli when applied directly to the nerves, apparently by causing in them rapid molecular changes. Also may be enumerated as chemical stimuli to the nerves substances found naturally in the body, as bile, bile salts, urea. The rapid withdrawal of water from nerve-tissue first increases, and then diminishes, its irritability. The imbibition of water decreases nervous irritability.

An electric current of less duration than the 0.0015 of a second does not stimulate the nerve-fibres. It would appear that more time is required for the electric current to excite in nerve-tissue the state of electrotonus which is necessary to the exhibition of its functional activity. The electric current stimulates a nerve most powerfully at the moments of entrance into and exit from the nerve, and the more abruptly this takes place the greater the stimulation. Thus the weak interrupted currents of the faradic or induced electricity owe their powerfully stimulating effects to the abruptness of their generation and entrance into and exit from the nerves. At the moment of the entrance of the electric current into the nerve—that is, upon closing the circuit—the stimulating effect is at the negative pole or cathode; when the current is broken—i.e. leaves the nerve—the stimulating effect is at the positive pole or anode. A current of electricity very gradually introduced into or withdrawn from a nerve does not stimulate it. But if while a current is passing through a nerve its density or strength be increased or diminished with some degree of rapidity, the nerve is stimulated, and the degree of stimulation is in proportion to the suddenness and amount of change in the density or strength of the current. Although with moderate currents the stimulation of the nerve takes place only upon their entrance and exit, or upon variations of their density, nevertheless, with a very strong current the stimulation continues during the passage of the current through the nerve. This is shown by the pain elicited in sensitive nerves, and the tetanic contraction of the muscles to which motor nerves are distributed.

An important factor in electrical stimulation is the direction of the current through the nerve. A current passed through a nerve at right angles with its length does not stimulate it. Currents passing through a nerve stimulate in proportion to the obliquity of their direction, the most stimulating being those passing along the length of the nerve. Motor nerves are more readily stimulated by the electric current the nearer it is applied to their central connection. Experiments on the lower animals would seem to indicate that the motor fibres in a nerve-trunk do not all show the same degree of irritability when stimulated by the electric current.

The irritability of the nerve-fibres may be modified or destroyed in various ways. Separation of nerves from their nutritive centres causes at first an increase of their irritability, which is succeeded by a diminution and total loss, these effects taking place more rapidly in the portions nearer the nerve-centres. It is important to observe that an increase of irritability preceding its diminution is generally observed in connection with the impaired nutrition of nerves, and is the first phase of their exhaustion.

Prolonged and excessive activity or disuse of nerves causes diminution of their irritability, which may go to the extent that neither rest in the one case nor stimulation in the other can restore it. If a galvanic current is passed through a nerve in its length, the irritability of the fibres is increased in the region of catelectrotonus—viz. in the part near the cathode—and diminished in the region of anelectrotonus—viz. in the part near the anode. Certain substances, as veratria, first increase and then destroy the irritability of the nerves; others, as woorara, rapidly destroy it.

The fibres of the peripheral nerves are divided into two classes: first, those which conduct impressions or stimuli to the nerve-centres, the afferent or centripetal fibres; and, secondly, those which conduct impulses from the centres to peripheral organs, the efferent or centrifugal fibres. Belonging to the first class are (1) sensitive fibres, whose stimulation sets up changes in the nerve-centres which give rise to a sensation; (2) excito-motor fibres, whose stimulation sets up in the nerve-centres changes by which impulses are sent along certain of the centrifugal fibres to peripheral end-organs, causing muscular contraction, secretion, etc. Belonging to the second class are (1) motor fibres, through which impulses are sent from the nerve-centres to muscles, causing their contraction; (2) secretory fibres, through which impulses from nerve-centres stimulate glands to secretion; (3) trophic fibres, through which are conveyed influences from the centres, affecting the nutritive changes in the tissues; (4) inhibitory fibres, through which central influences diminish or arrest muscular contraction or glandular activity. No microscopic or other examination reveals any distinction between these various fibres.