PAIN 



479 



Skin 



T 



Stimulating C 



electrodes (^ 





Recording 

 IQ electrodes 



I 



^^j^ L^^ 1^^^ ^|u^ k 



FIG. 6. Double nerve preparation from frog's skin show- 

 ing chemical transmission of impulse from one nerve to the 

 other. Antidromic stimulation of the peripheral end of one 

 cutaneous nerve was often evoked by electrical stimulation 

 of an adjoining cutaneous nerve with an overlapping field, 

 the responses appearing either during or after the antidromic 

 stimulation. The nature of the discharges is shown in the pho- 

 tograph of an action potential. Vertical while lines are synchro- 

 nous with shock aitefact and are go msec, apart; a succession 

 of two fast spikes appears 3 to 4 msec, later ; then one fast, four 

 slow, one fast and two slow impulses regularly succeed in the 

 recording electrodes following each stimulus to the other nerve. 

 Direct conduction from one nerve trunk to the other and 

 spread of current could be excluded. [From Habgood (i 13).] 



them to study effectively the pain produced by 

 chemical.s. The method has given them more con- 

 sistent results than intradermal injection or pricking 

 of the skin through a drop of solution on it. They have 

 demonstrated that tiny amounts of three identified 

 substances found in tissues provoke pain when applied 

 to the area exposed after removal of blistered skin. 

 Both acetylcholine and histamine in concentrations 

 of io~^ gm per ml, and 5-liydro.\ytryptaminc (sero- 

 tonin) even in amounts as low as io~* gm per ml 

 cause pain. The time of onset and duration of the 

 pain are different and characteristic for each of the 

 three. The two latter substances have already been 

 associated with injured tissue, serotonin with platelet 

 breakdown. Saline extracts of rat and human skin 

 made by these workers were found to contain 5 x io~^ 

 gm per ml of histamine and to cause prolonged pain 

 when applied to a blister base. Histamine alone in 

 such concentration caused only itching. 



The Keele group has found an additional pain- 

 producing substance (PPS) in the blister fluid itself 

 as well as in human plasma, serum and protein-rich 

 inflammatory fluids obtained from pleural, peri- 



toneal, joint or hydrocoele cavities (10). The PPS 

 shows the peculiar behavior of appearing in these 

 fluids only after they are 'activated' by contact with 

 glass; but following activation the capacity to evoke 

 pain declines rapidly to less than 10 percent of the 

 peak within an hour at room temperature. The pain- 

 producing activity of PPS correlates well with ability 

 to cause contraction of the isolated rat uterus. By 

 applications of this convenient method as well as 

 by other tests they showed PPS to be different from 

 serotonin and histamine and to resemble the poly- 

 peptide Ijradykinin more closely than any other sub- 

 stance yet tested. Bovine bradykinin produced pain 

 in man indistinguishable from that of PPS in concen- 

 trations as low as io~^ gm per ml. A continuation 

 of this type of study may lead to knowledge of the 

 actual substances which are stimulating pain endings 

 in vivo. In general the minutiae of the mechanisms 

 whereby stimuli are transduced into nervous impulses 

 remain wide open for investigation. 



POSTERIOR AND ANTERIOR ROOTS 



The distribution of the nerve fibers transmitting 

 pain via each posterior root has been largely worked 

 out for the cutaneous supply. Various diagrams of 

 these so-called dermatomes obtained by a number 

 of methods have been collected by White & Sweet 

 (296, pp. 26 to 30); such data are more fragmentary 

 for the deeper structures (296, pp. 22 and 23). The 

 possibility that afferent fibers may also enter the 

 cord by way of the anterior roots has continued to 

 be supported by bits of evidence over the past 75 

 years. White & Sweet (296, pp. 31 to 36) have col- 

 lected and analyzed their own and others' data on 

 this subject. Studies not mentioned in that account 

 include those of Maruhashi el al. (185), who measured 

 the .size of small myelinated fibers they found asso- 

 ciated with ganglion cells on the course of ventral 

 roots in cats. These practically coincided with their 

 afferent fibers "with wide receptive field" (discussed 

 above), and they regard it as "certain that these 

 fibers provide an exception to the Bell-Magendie 

 law." However, these fibers were stimulated by 

 touch rather than noxious maneuvers. We were un- 

 able to find a) record of any patient in whom an- 

 terior rhizotomy stopped pain unassociated with 

 muscle spasm, i) report of altered response to ob- 

 jective sensory tests after anterior rhizotomy or c) 

 written account of failure to stop pain by posterior 

 rhizotomv followed by success af*er a later anterior 



