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HANDBOOK OF PHVSIOLOG"i' 



NEUROPHYSIOLOGY 11 



as to why nerve section is followed by supersensitivity. 

 Although it is not impossible that the nerve terminals 

 might liberate, in addition to the chemical mediator, 

 some other substance of importance for the effector 

 cells, the concept of a trophic influence exerted by the 

 nerves is difficult to accept. The most reasonable ex- 

 planation seems to be that supersensitivity develops 

 owing to lack of transmitter stimuli. The arguments 

 and evidence against this view brought forth by 

 Cannon & Rosenblueth (77) do not seem to have 

 validity any longer. On the contrary, this explanation 

 has received strong support from the extensive studies 

 of the supersensitivity of salivary glands made by 

 Emmelin and his associates (cf. 128). The most perti- 

 nent results are that a supersensitivity, indistinguish- 

 able from that found after nerve section, may be 

 evoked in nondenervated glands by preventing the 

 chemical mediator from acting on the cells, and that 

 supersensitivity due to nerve section may be prevented 

 or abolished by exposing the cells to chemical stimuli 

 of a secretory nature. The concept of a trophic influ- 

 ence hardly seems compatible with these results. The 

 fact that supersensitivity is less pronounced after 

 decentralization than after denervation may, accord- 

 ing to this view, be explained as due to intermittent 

 release of small quantities of the transmitters from the 

 postganglionic nerve terminals (see the previous sec- 

 tion on activity independent of the central nervous 

 system) . 



In spite of much work, no theory has been elab- 

 orated which is able to give a satisfactory explanation 

 of the changes resulting in supersensitivity. Cannon 

 & Rosenblueth (75) once suggested an increased 

 permeability^ of the cells to be the basic change. 

 Although at least suggestive evidence for this theory is 

 available, the experimental data are difficult to ex- 

 plain on this basis. Burn and his associates have tried 

 in a series of investigations (62-66) to furnish evidence 

 for the hypothesis that supersensitivity is a conse- 

 quence of a decreased ability of the effector cells to 

 inactivate the chemical mediators. For some smooth 

 muscles it was found that the increase in sensitivity 

 a fter de nervation paralleled a fall in amine oxidase 

 and in cholinesterase, which clearly supported their 

 theory, but in other muscles no such correlation could 

 be demonstrated. This lack of correlation has also 

 been found by other investigators (10, 401). Another 

 difficult obstacle for the theory is that denervated 

 effectors develop hypersensitivity to many substances 

 quite unrelated to the natural transmitters. Some of 

 the nonspecific agents were shown to act indirectly 

 by liberation of an epinephrine-like substance, but 



the effects of other drugs may be more difficult to 

 explain (cf. 221, 222, 400). 



degener.-'lTign .\nd regener.^tion in PERIPHER.'\L 

 .\utonomig nervous system 



Degeneration 



The structural clianges initiated in autonomic nerve 

 fibers by transection are very similar to those of 

 somatic fibers, at least when examined with neuro- 

 histological methods. The myelin sheath, when pres- 

 ent as a microscopic structure, is retracted from the 

 nodes and broken up in fragments, the axon is frag- 

 mented and disintegrated, and finally both undergo 

 dissolution. There are many controversial statements 

 as to the degeneration of the autonomic nonmedul- 

 lated fibers and no systematic research has been done 

 on this matter. It is often stated that these fibers are 

 considerably more resistant than the myelinated. This 

 view was generally accepted in classical neurohistol- 

 ogy (28, 337, 349, 410). Ramon y Cajal (349), for 

 instance, stated that sympathetic nonmedullated 

 fibers do not disintegrate until 4 to 7 days after tran- 

 section. In many later studies it has been found, 

 however, that both pre- and postganglionic non- 

 medullated axons in the cervical sympathetic of the 

 rat, rabbit and cat show degenerative changes as 

 rapidly as large somatic nerve fibers and disintegrate 

 within 24 to 72 hours. This has been demonstrated 

 both ijy the silver impregnation technique (97, 103, 

 279, 282, 301) and by methylene blue staining (170, 

 206, 416). The nonmedullated fibers in fine skin 

 nerves also degenerate rapidly (434). It may well be, 

 however, that there are large differences between 

 different autonomic nerves. Some support for this 

 view is given by the varying reports on the functional 

 degeneration of sympathetic C fibers. There is evi- 

 dence, for instance, indicating that the sudomotor 

 fibers in the cat's paw may conduct impulses up to 

 6 days after nerve section (391). Such a long degenera- 

 tion time, however, may also be found in some in- 

 stances for preganglionic B fibers in the cat's cervical 

 sympathetic (see e.g. 168, 286). The responses ob- 

 tained on stimulation of degenerating autonomic B 

 (see below) and C (301, 416) fibers usually decline 

 rapidly to disappear within 2 to 4 days, but this is no 

 evidence for a loss of conduction. On the basis of the 

 available sparse and unsystematic reports, it is not 

 possible to decide whether the autonomic B and C 

 fibers differ markedlv from each other or from somatic 



