Procaine Block of the Sympathetic Nerves in the Study of Intractable Pain and Circulatory Disorders

PROCAINE BLOCK OF THE SYMPATHETIC NERVES IN THE STUDY OF INTRACTABLE PAIN AND CIRCULATORY DISORDERS JAMES

C.

WHITE,

M.D., F.A.C.S."

ALTHOUGH the use of drugs to produce insensibility to pain was dis; covered a hundred years ago, a very important by-product, their use in the selective block of the somatic and visceral nerves, has been developed in the past thirty years. This method of investigation has been particularly useful in advancing anatomical knowledge of viscerosensory and sympathetic motor innervation and in the practical application of this to the surgical treatment of intractable pain and peripheral vascular disease. Blocking the viscerosensory axones by paravertebral injection of procaine hydrochloride was first proposed by Kappis 1 and greatly advanced by the pioneer work of Uiwen,2 von Gaza,3 Mandl4 and Leriche,5 The method was first used in this hospital by me early in 1927 in the investigation of pain transmission in angina pectoris. Later, while working at Professor Leriche's clinic in Strasbourg, I was further impressed by its value and, on returning here in 1928, lost no time in putting it to wider use. In the intervening years Dr. R. H, Smithwick and I have blocked the visceral nerves with procaine extensively, This has enabled us to develop a number of operative measures for the relief of hitherto intractable forms of visceral pain. In addition, its adaptation for measuring the degree of vasoconstrictor tone in peripheral vascular disease was first proposed and developed here,6 It is the purpose of this paper to give an historical account of the development of these diagnostic methods and a summary of the clinical advances that have been made through their use by the surgical services of this hospital.

From the Massachusetts General Hospital, Surgical and Neurosurgical Services and the Harvard Medical School, Surgical Laboratories, Boston. This paper was presented at the One Hundredth Anniversary of the First Public Demonstration of Surgical Anesthesia, Massachusetts General Hospital, October 15, 1946. .. Chief, Neurosurgical Service, Massachusetts General Hospital; Assistant Professor of Surgery, Harvard Medical School. t In performing any paravertebral injection care must be exercised not to inject the anesthetic drug into a blood vessel, the pleura or the subarachnoid space. While several cases of injury to the spinal cord from alcohol have been reported,7 I am not aware of any complication more serious than the production of a temporary pneumothorax from procaine. I have also witnessed the production of a high spinal anesthesia in the course of an upper thoracic paravertebral block, but as only 50 mg. of procaine were injected and its presence in the subarachnoid space was detected immediately, no harm came of it. On the whole it is my opinion that paravertebral injection is safer and of greater value than subarachnoid block, where damage to the caudal roots 8 and arachnoiditis 9 are rare but extremely serious possibilities. 1263

1264

JAMES C. WHITE

2nd Position, Contact with Vertebral Body

~

1st Position, Contact with Transverse Process

------*

2nd Intercostal Nerye, Sympathetic Rami a Trunk

2ncl Rib - - - - - - - - - - - - - f t i

Fig. 389.-Technic of insertion of needles under x-ray control for injection of 'upper thoracic sympathetic ganglia.

PROCAINE BLOCK OF SYMPATHETIC NERVES

1265

This is no place for more than a brief comment on the technic and safeguardsf of injection, methods which have been described elsewhere in detail 10 , 11, 12,13 and which we have largely adapted from the excellent monograph of Labat.14 For increasing the accuracy of injec-

Psoas M . - - 2nd Position,Contact with Vertebral Body""

r

1st Position, Contact with Transverse Process

Sympathetic Trunk

2nd Lumbar N.-----1c\---'c'

Fig. 390.-Technic of insertion of needles for injection of lumbar sympathetic ganglia.

tion when permanent block is attempted with alcohol, Gentry arid F3 have found that visualization of the position of the needles by x-ray is a very helpful procedure. The placement of the needles for infiltrating the paravertebral ganglia is illustrated in Figures 389 and 390. By injecting small amounts (2 to 3 cc.) of 2 per cent procaine with adrenaline against the lateral surfaces of several vertebrae, one can interrupt the nerve supply of any desired viscus for a period of from one to two hours.

1266

JAMES C. WHITE

By using larger quantities (5 to 10 cc.) of 1 per cent procaine injected against the sides of every second vertebra, a very wide. temporary denervation can be obtained. Kappis's1 method of infiltrating the splanchnic nerves beneath the diaphragm, recently improved by de Souza Pereira,15 produces a block of the entire splanchnic bed and all the upper abdominal viscera. If, as deSous!j. Pereira has stated, "it is possible before operation to determine what result may be obtained ... this type of operation [sympathectomy] can attain a high degree of accuracy." By infiltrating the chain of sympathetic ganglia with procaine at different levels along the vertebral column, it has been possible to map the segmental origin of the motor-sensory fibers of all the viscera with considerable accuracy. Another great advantage of temporary diagnostic block is that it gives the patient, as well as the surgeon, a demonstration of what can be accomplished by the proposed operation. PARAVERTEBRAL PROCAINE BLOCK IN THE STUDY OF VISCERAL PAIN

.

In certain forms of visceral disease characterized by intractable pain the fundamental condition often cannot be corrected by standard medicalor surgical measures. Yet even under such circumstances much may be accomplished by an indirect neurosurgical attack on the afferent nerves which transmit painful impulses from the diseased organ. Examples 'of the conditions in which paravertebral block has been most helpful are severe angina pectoris, painful aneurysms of the aorta, cancer of the upper abdominal viscera, penetrating duodenal ulcer (in patients with advanced coronary disease), postoperative narrowing of the biliary ducts and pancreatic calculi. I shall point out briefly what we have learned at this hospital about viscerosensory innervation in these conditions by means of selective nerve block. Angina Pectoris.-Following the prediction of Franc,;ois-Franck16 that medically intractable angina pectoris could be relieved by sympathectomy, Jonnesc017 in 1916 first removed the cervical sympathetic ganglia. In his first patient the relief of pain was striking and complete, but in the large number of cervical sympathetic ganglionectomies performed by European and American surgeons18 . 19 in the following decade only slightly over 60 per cent obtained satisfactory relief. In addition to this the mortality rate was 20 per cent. At this hospital the early experience of Drs. E. P. Richardson and P. D. White20 with cervical sympathectomy gave even more disappointing results. By 1925 it had become obvious that the cause of surgical failure was incomplete anatomical knowledge of the pathways of pain from the heart. In that year, during the course of an operation for angina pectoris under local anesthesia, Leriche21 made a most important observation. Direct injection of the exposed stellate ganglion with procaine resulted

TABLE 1 CASES OF INTRACTABLE CARDIO-AoRTIC PAIN RELIEVED BY PARAVERTEBRAL BWCK AND SYMPATHECTOMY -

Condition

......

1>0

Angina pectoris

~

Number of Cases

Paravertebral Block

75*

Procaine and alcohol TcT,

Result ,

Excellent, 56%; fair, 21.3%; failure, 8%; classified, 6.7%; death, 8%.

Ull-

Thoracic ganglionectomy T,-T, Excellent in all, but a partial recurrence after a (by Drs. Mixter, Allen, and year in 1, and 1 operative death at 1 mo. White)

8

Aneurysm of aortic arch

Operation

2

Procaine and alcohol T c T,

Excellent to death at 3 mos. and 5 Y2 yrs.

1

Procaine alone

Excellent for last 6 weeks of life.

-

* Five of these injections were performed by Dr. W. J.

Mixter.

1268

JAMES C. WlllTE

in immediate relief of an attack' of severe cardiac pain which developed on the operating table. oJ In the same year the publication of Mandl's4 experience with paravertebral injection of procaine first suggested the presence of upper thoracic cardiac rami in addition to the classical cervical cardiac nerves. These delicate thoracic rami, which run from the upper three or four thoracic sympathetic ganglia to the posterior cardiac plexus, have since been demonstrated in anatomical dissections by Braeucker,23 Jonnesco and Enarchesco,24 and Kuntz and Morehouse. 25 Their physiological importance in pain conduction from the heart has been proven by animal experiments of White, Garrey and Atkins 26 and by .subsequent clinical experience. It is now generally recognized that they constitute an important accessory pathway for the conduction of pain from the heart. Soon after Mandl's important paper Swetlow27 described the use of alcohol to secure a lasting interruption of all the cardiosensory fibers. Chemical block by paravertebral injection has now been used in seventy-five cases at this hospital. Results in this group are summarized in Table 1. At first we routinely used diagnostic injection with procaine before attempting a permanent block with alcohol. Today, after twenty years' experience, we are so sure that all the sensory pathways from the heart run through the upper three or four thoracic sympathetic ganglia (Fig. 391) that we no longer believe that a preliminary diagnostic block with procaine is necessary unless anginal pain is referred to unusual areas .. Furthermore, during this twenty-year experience Dr. E. M. Bland and 122 have been convinced that in all but the poorest risk cases direct surgical intervention should be used, either by resection of the upper three thoracic sympathetic ganglia or by posterior rhizotomy. Today paravertebral alcohol injection is reserved only for the poorest risk cases. It fails to give effective block of cardiac pain in some 8 per cent of cases and is followed by troublesome intercostal neuralgia in 10 per cent. Recurrence secondary to nerve regeneration has been relatively rare (18 per cent) and usually mild. On the other hand, resection of the upper three or four thoracic sympathetic ganglia or cutting the corresponding posterior spinal roots is nearly certain to give permanent relief. Although the injection method for control of the most severe cases of angina pectoris has been largely superseded, we have nevertheless learned a great deal from our extensive early experience. Intractable Pain in Aneurysms of the Thoracic Aorta.-Most aortic aneurysms are not acutely painful but cause symptoms only through pressure on neighboring structures. At times, however, they may produce intense suffering. In our experience this has been paroJ Leriche attributed this cIearcvt inte~ption of pain to paralysis of the coronary vasoconstrictor fibers rather than to interruption of the sensory pathway. Modern evidence, however, favors the latt~r theory~22

PROCAINE BLOCK OF SYMPATHETIC NERVES

1269

ticularly true when the aneurysm is situated in the aortic arch and is expanding upward into the outlet of the thorax. It would be logical to suppose that under these circumstances the pain is caused by pres-

..u:..

.., ::Z;:,;~;.':;;d#::;:::' Intercostal N.

Paravertebral Sympathetic Ganglion I-Superior Cervical Ganglion 2- Middle 3-lnferior

-T.1.

-T 3.

Fig. 391.-Anatomical diagram of the cardiac afferent fibers from the heart.

sure on the parietal pleura and the intercostal nerves. In order to test the pathway of pain sensation White28 performed diagnostic procaine block in three patients with large and intensely painful aneur-

1270

JAMES C. WHITE

ysms of the aortic arch. The first case was particularly interesting because the pain was referred to the right upper chest, shoulder, neck, and scalp-that is, over the cervical as well as the highest intercostal nerves (Fig. 392). All pain was relieved for thirty-six hours by paravertebral procaine injection of the first and second thoracic ganglia, although there was no detectable anesthesia of the skin. A subsequent injection with 95 per cent alcohol gave the patient com-

Fig. 392.-X-ray of large aneurysm of ascending arch of aorta which caused continuous intense pain referred to stippled areas in photographs. Needles were inserted at points 1 and 2 against the sides of the two upper thoracic vertebrae. Procai~e block gave immediate temporary relief and lasting interruption of pain followed subsequent injection of alcohol.

plete relief for the remaining three months of his life. In this instance right-sided pain wa§ caused by an aneurysm of the ascending arch of the aorta, whereas in the two subsequent cases the aneurysms involved the transverse and descending portions of the arch. Here the pain was left-sided. These three patients were all given satisfactory relief, which in the case of the longest survivor lasted until his death five and one-half years later. Reichert 29 has relieved the pain from

PROCAINE BLOCK OF SYMPATHETIC NERVES

1271

an aneurysm in the lowest portion of the descending arch of the aorta by injecting the second to sixth thoracic sympathetic ganglia. Eleven months after injection this patient remained free of pain and had returned tOt active work. Another successful case has been reported by Rasmussen and Farr.30 Intractable Pain in Disease of the Upper Abdominal Viscera.Chronic disease of the upper abdominal viscera may be intensely painful and injurious to the patient's morale. Formerly division of the posterior sensory spinal roots or section of the anterolateral pain tract in the spinal cord were the only neurosurgical methods which could relieve continuous suffering and prevent addiction to morphine. Investigation by paravertebral block in the last fifteen years has shown that such radical surgery is often unnecessary and can be superseded by more selective resection of the lower thoracic ganglia and splanchnic nerves. Ordinarily resection of these structures, as is done in the surgical treatment of hypertension, has been the procedure of choice, but at times the general condition of the patient was so poor, owing to the cachexia of advanced malignancy or coronary disease, that no form of major surgery was possible. A number of patients in this precarious state have been given comfort for the remainder of their lives by chemical block of the paravertebral ganglia with procaine and alcohol. Outstanding contributions in this field of intractable visceral pain have been made in France by Leriche5 and his pupil Luzuy,31 and by Mallet-Guy and Guillet of Lyons. 32 The experience of Dr. R. H. Smithwick and myselflO in the localization of the upper abdominal sensory pathways by paravertebral procaine block and their subsequent permanent interruption is summarized in Table 2. Examination of these data shows that many of these painful states represent new and unusual problems. While relief could have been obtained by high anterolateral cordotomy, some of these patients would have been extremely poor operative risks, and in all interruption of the viscerosensory nerves was a far simpler and less mutilating procedure. However, without preliminary demonstration of the rami concerned with the conduction of pain by paravertebral block this type of selective viscerosensory neurectomy would never have been possible. In addition to the chronic varieties of upper abdominal pain produced by known visceral disease, Archibald,33 Scrimger34 and Dr. W. J. Mixter and J35 have encountered certain cases of obscure abdominal pain where even exploratory laparotomy had failed to demonstrate the causative factor. In a number of instances of this sort, where the pain recurred at frequent intervals and required large doses of morphine for relief, paravertebral procaine block has stopped the attacks. Following such a favorable indication a number of brilliant results have been achieved by lower thoracic sympathectomy and splanchnicectomy, after all other forms of medical therapy and numerous

TABLE 2

CAsEs OF INTRACTABLE ABDOMINAL PAIN REi.mVED

BY PARAVERTEBRAL BLOCK AND SYMPATHECTOMY ----

No. of Cases

Paravertebral Block

Posterior duodenal ulcer with R.upperquadrantand erosion into pancreas. Ad- back. vanced coronary disease prevented resection of ulcer. (Smithwick)

2

Procaine and alcohol ToT. (R)

Irritable colM· with constipa- Agonizing attacks of tion. abnonlial peristalsis. and abdominal colic. vomiting. (Smithwick)

1

Procaine L. and 1... Bilateral sjilanchnicec- Complete relief. bilateral. tomy and resection of upper lumbar ~pathetic ganglia.

Metastatic carcinoma of liver Continuous pain in R. following radical mastectomy. side of abdomen in (White) . woman sensitive to morphine.

1

Procaine and alcohol T.-TIt (R)

Post-operative~stenosis of biliary

1

R. splanchnicectomy Complete relief. Procaine block splanchnic rami (R) and resection of lower thoracic sympathetic ganglia.

2

Procaine. T.-TIl (R) R. splanchnicectomy Excellent result in 1st case. followed by relief for and resection of 6 In 2nd. relief of pan2 hours. lower thoracic sym- creatic pain appeared eCpathetic ganglia. fective at 1 mo.• but was oompliClfted by intercostal neuralgia. Patient could not be followed longer.

Cause of Pain

~

Location of Pain

R. upper quadrant.

duets (Smithwick) Multiple Jk.1creatic ('.aIculi.· R. upper quadrant and (Smithwi • Moore anclWhite) .~ank. . ... "

Operation

- -

• A recent article by Dr. Mallet-Guy of Lyons reports similar successful relief of pancreatic pain.

Result Complete relief: Case 1: Until death from coronary thrombosis at 11 mos. Case 2: Until last report at 8 mos.

Complete relief for remaining 2 weeks of life.

TABLE 3 CASES OF INTRACTABLE PERIPHERAL NEURALGIA RELIEVED BY PARAVERTEBRAL BLOCK AND SYMPATHECTOMY -

6ondition

Number of Cases

Causalgia following peripheral nerve injury

14

.':'-

-

Posttraumatic arthritis with vo osteoporosis.

Result

Diagnostic procaine block in Preganglionic upper thoracic or' Complete relief in 13, partial relief in I, no all. lumbar sympathectomy. deaths or serious complications. (Drs. White, W. Heroy and E. Goodman.) Permanent relief in 1st patient following carpal . fracture after 3 injections. Permanent relief in 2nd patient with carpal fracture following single procaine block.

Procaine block only. (Drs. H. H. Faxon and White)

1

Diagnostic procaine block. Resection L-La ganglia. (Dr. E. Hamlin, Jr.)

2

Diagnostic pr6caine block.

1

Diagnostic procaine blocks Resection L, and L, ganglia.

~

,

Operation

2

to

Amputation ,,' stumpneuralgia.

Paravertebral Block

----

Complete relief in patient with Sudeck's atrophy of ankle and foot without trauma.

Upper thoracic sympatheCtomy. 'Excellent results following upper thoracic ganglionectomy in 2 men with painful finger stumps. One had partial recurrence following return of vasoconstrictor tone . . Permanent relief of painful amputation stump of great toe.

1274

JAMES C. WHITE

ill-advised abdominal operations had failed. In a case in which an operation was performed by Dr. Mixter and me the patient has remained well for six years. In testing out unusual varieties of pain of any sort it is advisable to repeat the injection of procaine on more than one occasion and '8.1so to make sure that inert saline is not equally effective. In many of these cases of obscure pain, especially when complicated by drug addiction, it is essential to make certain that the complaints are not, in part at least, the result of a functional disturbance. It is only by taking precautions of this sort that failures can be avoided and the patient's morale not be further impaired by ill-advised surgery. In general, however, we have been pleasantly surprised to find how often the neurotic appearing victim of intractable visceral pain has responded and been transformed into a stable individual as soon as his chronic discomfort has been relieved. Paravertebral Procaine Block in the Study of the Post-traumatic Neuralgias.-The intense discomfort of causalgia/o post-traumatic arthritis with osteoporosis,36. 37 and the diffuse aching or burning pain that sometimes follows peripheral amputationsO in individuals with chronic cold, sweaty extremities39 can often be relieved by paravertebral procaine block (Table 3). The publications of Leriche5 and Luzuy31 on this subject are of particular interest and should be read by all surgeons who are concerned with these problems. Some of the more fortunate cases, especially those with post-traumatic arthritis and others classified by Homans 40 as «minor causalgia," may recover after one or more paravertebral injections of procaine. Others in whom the pain is effectively, but only temporarily, abolished can be counted on to obtain permanent relief from a suitable sympathectomy. In all intractable cases of this sort, in which the pain has become chronic and disabling, preliminary injection with procaine is an extremely important procedure, as it indicates· with a high degree of certainty which individuals will do well with chemical or surgical interruption of the sympathetic fibers. The criteria for evaluating the role of the sympathetic innervation in the post-traumatic neuralgias, which should be followed with care, are as follows: (1) Relief during the period of effective sympathetic block with procaine must be complete. (2) The persistence of relief for a period of over two hours indicates that repeated injections may '" Instances of successful interruption of severe neuralgia in upper ann or thigh amputations by paralyzing the sympathetic outflow are extremely rare. Livingston38 has reported a successful result from paravertebral procaine injection in a physician with an extremely painful upper ann stump. One of my few failures, however, has occurred in a case of mid-thigh amputation, where lumbar sympathectomy was perfonned on the strength of a successful block with procaine. It may be pointed out in this connection that sympathetic vasoconstriction above the elbow or knee is extremely slight.

PROCAINE BLOCK OF SYMPATHETIC NERVES

1275

result in further improvement with more prolonged periods of freedom from discomfort and that ultimate lasting recovery may be attained without recourse to actual operation. (3) When sympathetic block with procaine has given complete relief for only a short interval, upper thoracic sympathectomy or resection of the lumbar ganglia is , reasonably certain to succeed. In the case in which diagnostic block has been followed by no response, sympathectomy is not likely to succeed and some other course of treatment should be adopted. Experience in the recent war 41 , 42, 43 has further emphasized the importance of preliminary procaine block in order to avoid useless operations, as these invariably lead to a further deterioration of the patient's morale. 44 Some of the results at the Massachusetts General Hospital and my personal experiences at two Naval hospitals are summarized in Table 3 and have been recorded in further detail in other publications. 45 , 46, 47 PROCAINE BLOCK OF THE VASOCONSTRICTOR FIBERS

In 1930 I reported that the sympathetic vasomotor fibers could be blocked temporarily by procaine as effectively as by direct operation. 6 ,48 Two preliminary papers, following a year's period of clinical use, showed that maximal vasodilatation can be brought about by paralyzing the sympathetic fibers in the anterior spinal roots (spinal anesthesia), by injecting procaine around the upper thoracic or lumbar sympathetic ganglia (paravertebral block) or by infiltrating the vasoconstrictor axones in' the principal nerves to the extremities (peripheral nerve block). A few weeks before the appearance of the first paper Brill and Lawrence 49 reported the use of spinal anesthesia for determining the degree of vasoconstriction in the lower extremities, and shortly thereafter Morton and Scott50 published further studies showing the value of spinal block. Later they advocated peripheral injection of the posterior tibial, ulnar or median nerves as the simplest method of estimating the vasodilator response. A year previously Sir Thomas Lewis 51 had advocated blocking the ulnar nerve at the elbow to determine the rise of temperature in the little finger. In our experience this last method is less reliable than the other two, especially in states of occlusive vascular disease, where dilatation of collateral arteries in the proximal portion of the limb is of great importance. These methods have stood up well under the test of time and continue to be the most effective tests for determining the degree of vasoconstrictor tone and differentiating between states of excessive vasoconstriction and occlusive vascular disease. Except for the recent substitution of differential spinal block for full spinal anesthesia, a method devised at this hospital by Sarnoff and Arrowood,52 there have been no important modifications in these procedures.

1276

JAMES C. WHITE

All of these methods temporarily paralyze the tonic sympathetic vasoconstrictor impulses. and give a quantitative measure of the elevation in peripheral temperature which can be expected to follow sympathectomy. We have .come to feel that paravertebral block is the best of all the available methods of testing the degree of vasoconstriction. It is safer thith spinal anesthesia, less disturbing to the ' patient than the earlier method of vasodilatation induced by intrave. nous injections of foreign protein, and more sure to result in maximal release of vasoconstrictor tone than either peripheral nerve block or body heating. The method demonstrates to the patient as well· as the surgeon the degree of warming, as well as the elimination of increased sweating, which bothers so many individuals with excessively cold, discolored and clammy extremities. In typical Raynaud's disease it will demonstrate the case with a serious degree of endarteritis of the digital vessels secondary to scleroderma. In patients who are free from serious obliterative endarteritis the results of lumbar block tally quite exactly with the permanent temperature levels following resection of the lumbar ganglia, but the: teinporary rise in cutaneous temperature induced in the fingers and hand is somewhat. greater than the permanent result of sympathectomy. In thromboangiitis obliterans and arteriosclerosis the experience of the Peripheral Vascular Clinic has shown that our earlier hopes for an accurate prediction of the ultimate postoperative improvement in circulation have not been consistently borne out. While some 90 per cent of patients with obliterative vascular disease in whom the popliteal pulse is present will show a rise in temperature of the foot following paravertebral or spinal block, when the popliteal pulse is absent the great majority will have no post-injection rise. Nevertheless, some 40 per cent of this group will have a good response following resection of the three upj)ar lumbar sympathetic ganglia. It is evident that a vasoconstrictor block of short duration does not permit full development of blood :How through patent small collateral vessels. Perhaps this difficu1ty·will be overcome through the production of safe, longer-lasting anesthetic drugs. SUMMARY AND CONCLUSIONS

1. Diagnostic injectiqn with procaine hydrochloride is a valuable method for studying ti!e pathways over which unusual varieties of pain are transmitted to the brain and for determining the role of vasoconstriction in states of poor circulation in the extremities. . 2. Paravertebral block of the viscerosensory and s:0npathetic vasomotor fibers and their. iIlfiltration within the subaracjhnoid space and in the mixed spinal ne1'ves are described and evaluated.

PROCAINE BLOCK OF

S~PAT~C

NERVES

1277

3. Thanks to investigation with paravertebral block, it has been possible to develop effective methods of viscerosensory denervation which carry a minimum of risk and do not disturb cutaneous sensation. 4. Statistical data are presented which demonstrate the high degree of effectiveness of sympathectomy after temporary relief of pain by paravertebral injection of procaine. Intractable painful states which can be relieved by these means include angina pectoris, aortic aneurysm, certain lesions of the gastrointestinal tract, distention of the biliary and pancreatic ducts, causalgia, painful osteoporosis and some types of painful amputation stumps. 5. Procaine block of the sympathetic fibers serves to differentiate states of excessive vasoconstriction from arterial occlusion. Temporary release of vasoconstrictor tone, however, often fails to detect the case with occlusion of the major arteries which will show a gradual favorable response through permanent dilatation of patent collateral vessels. ACKNOWLEDGMENT

It is a great pleasure to acknowledge my debt to Rene Leriche, professor at the College de France and member of the Institut, in whose laboratory in Strasbourg the inspiration for this study was obtained. I also wish to express my sincerest thanks to Dr. R. H. Smithwick for permitting me to include many of his cases in this paper; more particularly, for his constant interest and stimulating help in these problems of pain while he was a member of the staff of this hospital. Dr. Chester M. Jones and Dr. William P. Chapman have been particularly helpful in the study of cases of visceral pain, and I ;want to take this occasion to express my gratitude to them for their interest and help in this field. The expenses of following up these cases were defrayed by a grant from a research foundation that wishes to remain anonymous. REFERENCES

1. Kappis, M.: Weitere Erfahrungen mit der Sympathektomie. Klin. Wchnschr., 2:1441-1446, 1923. 2. Liiwen, A.: Weitere Erfahrungen liber paravertebrale Schmerzaufhebung zur Differentialdiagnose von Erkrankungen der Gallenblase, des Magens, der Niere und des Wurmfortsatzes sowie zur Behandlung postoperative Lungenkomplikationen. Zbl. Chir., 50:461-465, 1923. 3. von Gaza, W.: Die Resektion der Paravertebralen Nerven und die isolierte Durchschneidung des Ramus Communicans. Arch. f. klin. Chir., 188:479500, 1924. 4. Mandl, Felix: Die Anwendungsbreite der ,paravertebralen Injektion. Klin. Wchnschr., 4:Nr.49, 1925. 5. Leriche, Rene: La Chirurgie de la Douleur. Paris; Masson & Cie., 2nd edition, 1940, 559 pp. 6. White, James C.: Diagnostic Blocking of Sympathetic Nerves to Extremities with Procaine: A Test to Evaluate Benefit of Sympathetic Ganglionectomy. J.A.M.A.,. 94:1382-1388, 1930. . 7. Molitch, Matthew and Wilson, George: Brown-Sequard Paralysis Following a Paravertebral Alcohol Injection for Angina Pectoris. J.A.M.A., 97:247, 1931.

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8. Ferguson, Fergus R. and Watkins, K. H.: Paralysis of the Bladder and Associated Neurological Sequelae of Spinal Anaesthesia (Cauda Equina Syndrome). Brit. J. Surg., 25:735-752, 1938. 9. Kennedy, Foster, Somberg, Harold M. and Goldberg, Bernard R.: Arachnoiditis and Paralysis Following Spinal Anaesthesia. J.A.M.A., 129:664-667, 1945. 10. White, James C. and Smithwick, Reginald H.: The Autonomic Nervous System: Anatomy, Physiology, and Surgical Application. New York, Macmillan Co., 2nd ed., 1941, 469 pp. 11. White, James C.: Surgery of Sympathetic Nervous System. Section 6, Chapter 19, of "Surgical Treatment of the Nervous System," edited by Bancroft and Pilcher. Philadelphia, J. B. Lippincott Co., 1946, pp. 457-504. 12. White, James C.: Technique of Paravertebral Alcohol Injection: Methods and Safeguards in Its Use in the Treatment of Angina Pectoris. Surg., Gynec. & Obst., 71:334-343, 1940. 13. White, James C. and Gentry, Robert W.: Radiographic control for paravertebral Injection of Alcohol in Angina Pectoris. J. Neurosurg., 1:40-44, 1944. 14. Labat, Gaston: Regional Anesthesia, Its Technic and Clinical Application. Philadelphia, W. B. Saunders Co., 1924, 496 pp. 15. de Sousa Pereira, A.: Blocking of the Splanchnic Nerves and the First Lumbar Sympathetic Ganglion: Technic, Accidents and Clinical Indications. Arch. Surg., 53:32-76, 1946. 16. Francrois-Franck, C. C.: Signification physiologique de la resection du sympathique dans la maladie de Basedow, l'epilepsie, l'idiotie et Ie glaucome. Bull. Acad. de med. Paris, 41:565-594, 1899; Recherches sur la sensibilite de l'appareil sympathique cervico-thoracique. J. physioI. et de path. gen., 1:724-738, 1899. 17. Jonnesco, Thomas: Le Sympathique Cervico-Thoracique. Paris, Masson et Cie, 1923,91 pp. 18. Fontaine, R.: Les Resultats Actuels du Traitement Chirurgical de l'Angine de Poitrine. Strasbourg, Les Editions Universitaires, 1925, 232 pp. 19. Cutler, Elliott C.: The Present Status of the Treatment of Angina Pectoris by Cervical Sympathectomy. Ann. Clin. Med., 5:1004-1013, 1927. 20. Richardson, E. P. and White, P. D.: Sympathectomy in the Treatment of Angina Pectoris: Comparison of Results with Those from Paravertebral Alcohol Injection. Am. J. M. Sc., 177:161-178, 1929. 21. Leriche, Rene: Recherches experimentales sur l'angine de poitrine. Presse med., 33:1361, 1925. 22. White, James C. and Bland, Edward F.: The Surgical Relief of Severe Angina Pectoris: Methods Employed and End Results in 83 Patients. To be published. 23. Braeucker, W.: Der Brustteil des vegetativen Nervensystems und seine klinisch-chirurgische Bedeutung. Beitr. z. Klin d. Tuberk., 66:1-65, 1927. 24. Jonnesco, T. and Enarchesco, M.: Nerfs cardiaques naissant de la chaiIw thoracique du sympathique, au-dessous du ganglion stellaire: Les nerfs cardiaques thoraciques chez quelques mammiferes. C. R. Soc. BioI., Paris, 97:977-980, 1927. . 25. Kuntz, A. and Morehouse, A.: Thoracic Sympathetic Cardiac Nerves in Man: Their Relation to Cervical Sympathetic Ganglionectomy. Arch. Surg., 20: 607-613, 1930. 26. White, James C., Garrey, Walter E. and Atkins, James A.: Cardiac Innervation: Experimental and Clinical Studies. Arch. Surg., 26:765-786, 1933. 27. Swetlow, G. I.: Paravertebral Alcohol Block in Cardiac Pain. Am. Heart J., 1:393-412, 1926.

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28. White, J. C.: Painful Aneurysms of the Aortic Arch: Relief by Paravertebral Injections of Procaine and Alcohol. J.A.M.A., 99:10--13, 1932." 29. Reichert, Frederick L.: Personal communication. 30. Rasmussen, Theodore and Farr, Walter J.: Paravertebral Injection of Procaine for Pain Produced by Aortic Aneurysm. Case report. J. Neurosurg., 3:267270,1946. 31. Luzuy, Maurice: Les Infiltrations du Sympathique: Physiologie, Indications, Techniques. Paris, Masson et Cie., 1946, 200 pp. 32. Mallet-Guy, Pierre and Guillet, Rene: Documents experimentaux et cliniques sur l'innervation des voies biliaires. Rev. Malad. Foie, 1944, No. 1. 33. Archibald, E.: Effect of Sympathectomy upon the Pain of Organic Disease of Arteries of the Lower Limbs and for Obscure Abdominal Pain. Ann. Surg., 88:499-509, 1928. 34. Scrimger, F. A. C.: On the Possibility of Relieving Abdominal Pain by Section of the Sympathetic Rami Communicantes. Canad. M. A. J., 21:184-189, ' 1929. 35. Mixter, William Jason and White, James C.: Pain Pathways in the Sympathetic Nervous System: Clinical Evidence, Arch. Neurol. & Psychiat., 25: 986-994, 1931. 36. Leriche, Rene and Fontaine, Rene: Des osteoporoses douloureuses post-traumatiques. Presse med., 38:617-621, 1930. 37. de Takats, Geza and Miller, Donald S.: Post-traumatic Dystrophy of the Extremities: A Chronic Vasodilator Mechanism. Arch Surg., 46:469-479, 1943. 38. Livingston, W. K.: Pain Mechanisms: A Physiologic Interpretation of Causalgia and Its Related States. New York, Macmillan Co., 1943, 253 pp. 39. White, James C.: Pain Mter Amputation and Its Treatment. J.A.M.A., 124: 1030--1035, 1944. 40. Homans, John: Minor Causalgia: A Hyperesthetic Neurovascular Syndrome. New England J. Med., 222:870-874, 1940. 41. Ulmer, Jack L. and Mayfield, Frank H.: Causalgia: A Study of 75 Cases. Surg., Gynec. & Obst., 83:789-796, 1946. 42. Rasmussen, Theodore B. and Freedman, Howard: Treatment of Causalgia: An Analysis of 100 Cases. J. Neurosurg., 3:165-173, 1946. 43. Allbritten, Frank F. and Maltby, George L.: Causalgia Secondary to Injury of the Major Peripheral Nerves. Surgery, 19:407-414, 1946. 44. White, James C.: Pain Following Injuries of Peripheral Nerves. U. S. Nav. M. Bull., 45:845-858, 1945. 45. White, James C.: Painful Injuries of Nerves and Their Surgical Treatment. Am. J. Surg., 72:468-488, 1946. 46. White, James C., Heroy, William W. and Goodman, Edmund N.: Causalgia Following Gunshot Injuries of Nerves: Role of Emotional Stimuli and Surgical Cure Through Interruption of Diencephalic Efferent Discharge by Sympathectomy. To be published. 47. Goodman, E. N., MeSSinger, W. J. and White, }. C.: Indications and Results of Surgery of the Autonomic Nervous System in Naval Personnel. Ann. Surg., 124:204-217, 1946. 48. White, James c.: Diagnostic Novocaine Block of the Sensory and Sympathetic Nerves: A Method of Estimating the Results Which Can Be Obtained by Their Permanent Interruption. Am. J. Surg., 9:264--277, 1930. 49. Brill, S. and Lawrence, L. B.: Changes in Temperature of the Lower Extremities Following the Induction of Spinal Anaesthesia. Proc. Soc. Exper. BioI. & Med., 27:728-731, 1930. 50. Morton, J. J. and Scott, W. J. M.: The Measurement of Sympathetic Vasoconstrictor Activity in the Lower Extremities. J. CHn. Investigation, 9:235-246, 1930.

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51. Lewis, Thomas: Experiments Relating to the Peripheral Mechanism Involved

in Spasmodic Arrt~~~ of the Circulation in the Fingers, a Variety of Raynaud's Disease. Heart, 15:7-101, 1929. 52. Sarnoff, Stanley J. liJ:tld Arrowood, Julia G.: Differential Spinal Block: A Preliminary Report. Surgery, 20:150-159, 1946.