RC 412 .n47 Copy 1 n^ ' ^^:\^\i^^^^ r«5**S fh ^; I 4. #- .-7 >' .^ - r>.>. K R.w LIBRARY Of CONGRESS. UNITED STATES OF AMERICA. THEINE TREATMENT OF NEURALGIA PHYSIOLOGICAL CONTRIBUTION TO THE THERAPEUTICS OF PAIN. THOMAS J.' MAYS, M. D., PROFESSOR OF DISEASES OF THE CHEST IN THE PHILADELPHIA POLYCLINIC; MEMBER OF THE PHILADELPHIA COLLEGE OF PHYSICIANS, OF THE PHILADELPHIA COUNTY MEDICAL SOCIETY, ETC., ETC. If*' PHILADELPHIA: P. BLAKISTON, SON & CO., IOI2 Walnut Street. 1888. 1^ Copyright, 1888, By THOMAS J. MAYS. PRESS OF WM F FELL & CO., 1220-24- SANSOM ST., PHILADELPHIA. TO DR. EDWARD R. MAYER, Of Wilkesbarre, Pennsylvania, IN APPRECIATION OF HIS EMINENT PROFESSIONAL ABILITY, AND IN GRATEFUL REMEMBRANCE OF HIS MANY DEEDS OF PERSONAL KINDNESS TO THE AUTHOR, ^])i8 liiih holumt is 3^t5ptctfulb Stiicat^iJ. PREFACE. This essay on Theine originally appeared in the Polyclinic, from September, 1887, to Feb- ruary, 1888 ; and in order to give the research which has been made of this drug a more per- manent place in medical literature, it was deemed proper to publish it in a separate little volume. Herewith I desire to express my warmest thanks to those of my medical friends who have been kind enough to report to me the results which they obtained in the clinical em- ployment of theine ; for I feel that the practical value which this investigation possesses is chiefly due to this part of the contribution. T. J. M. 1829 Spruce Street, Phila., March jth, 1888. CONTENTS. CHAPTER I. PAGE Introduction — Theine, 9 CHAPTER n. The Physiological Action of Theine, . . . i i CHAPTER HI. The Special Therapeutic Indications for the Use of Theine, -29 CHAPTER IV. Neuralgia, 39 Appendix, 81 Index, S;^ INTRODUCTION. CHAPTER I. THEINE The tea-plant, from which theine is obtained, is a shrub from twenty to thirty feet high, and is indigenous to the southern part of Asia, but is extensively cultivated in China, Japan, and in South America, as well as to a small extent in the United States. Its use as a beverage dates from a very early period in Chinese history, but the Greeks and Romans were ignorant of its existence, and it was only introduced into Eu- rope about the year 1657. The botanical origin of tea is Thea Bohea, T. viridis, T. sinensis, and T. assamica, and a few hybrids ; and the many varieties of tea in the market are prepared by selecting young or old leaves, and subjecting them to various processes of treatment. Tea B 9 lO HISTORY OF THEINE was probably first used for medicinal purposes. It is a common custom of our own day to apply tea leaves for the purpose of reducing inflamma- tion and allaying pain. Theine, to which tea principally owes its vir- tues, is an alkaloid, and was first found in the leaves of Chinese tea by Oudry, in 1827. This discovery was confirmed by Miilder and Jobst, in 1838, who believed it to be identical with caffeine and guaranine. Its chemical formula is CgHioN^Og, and it is known as trimethyl- xanthine. It occurs in snow-white, needle- like crystals, is almost tasteless, but produces a slight tingling on the end of the tongue, which is immediately followed by a temporary local anaesthesia. It is soluble in fifty parts of cold, but more soluble in warm water. CHAPTER II. THE PHYSIOLOGICAL ACTION OF THEINE My first experiments with theine were made in the spring and summer of 1885, and were pubhshed in the Therapeutic Gazette for Sep- tember, 1885, under the title of The Physiologi- cal and Therapeutic Actioji of Caffeine, Theine, and Guaranine. At this time I was ignorant of the fact that theine, caffeine, and guaranine were manufactured indiscriminately from coffee, tea, kola nut, Paraguay tea and guarana ; and that they were all sold out of the same bottle and labeled according to the demands of the trade ; but I supposed that I was using theine made from tea leaves, and caffeine from coffee beans. Inquiry, however, soon undeceived me afid demonstrated very positively that nearly all of that which is sold under the name of caf- feine at present is not caffeine at all, but theine, II 12 PHYSIOLOGICAL ACTION since it so happens that it is cheaper to manu- facture the alkaloid out of tea leaves than from any of the other raw materials. Moreover, it was further found that very little, if any, theine or caffeine is manufactured in this country, and that these agents are principally imported from Europe. Of course, under these circumstances, it was quite evident that the article which I used for theine must have emanated from tea, but on account of the uncertain nature of that which I used for caffeine I determined to review all my previous work on this subject. That I used two different agents was quite certain, for I could not have obtained the varying results in my experi- ments which I did if they had been alike in composition. Therefore Mr. William C. Harris, then with Messrs. Henry C. Blair's Sons, kindly undertook to manufacture both alkaloids for me from tea and coffee, respectively, and quite recently I also received the same alkaloids, made from the same sources, from Merck, of OF THEINE 13 Darmstadt, who, since my second series of ex- periments, has informed me that he will in the future manufacture these alkaloids separately — hence in ordering from him it is necessary to specify the alkaloid which is wanted. I fully reviewed my former work, and the net result confirms the conclusions drawn from the first series, and I have even found reason for believ- ing that the difference between the action of the two alkaloids in regard to sensation is greater than my earlier experiments indicated. The gross effects of tea and coffee on the animal economy have always been regarded as dissimilar, but their alkaloids have, until quite recently, been universally considered identical in their action. The supposed iden- tity of action of the two latter agents can only be explained on the score that, after once having been shown that they are chemically alike, the assumption naturally followed that they must also be alike in their physiological action. This view of their supposed identity 14 PHYSIOLOGICAL ACTION of action has also been encouraged by Aubert, Albers, Amory, Bennett, McKendrick, Burnett and others who investigated the drugs experi- mentally, although Leven, as far back as 1868, showed that theine produced convulsions in frogs while caffeine did not ; and that the lethal dose of theine was larger than that of caffeine. One important reason why the results of Leven differ so materially from those derived by others lies in the fact that he used the genuine alkaloids produced separately from tea and coffee, which does not appear to have been the case with the other experi- menters. Moreover, in view of the fact that the effects of theine and caffeine were believed to be the same, it is very difficult to obtain evidence as to the action of either agent. Toxi- cologically, we know more about caffeine than we do about theine, for, since coffee is much more powerful than tea, it has occasionally been employed for criminal purposes. A detailed account of the large number of OF THEINE 15 experiments which I made with these agents will not be given here, since they would swell this little work to undue dimensions ; but their condensed results, which appear below, demon- strate that, while the actions of theine and caffeine agree in many respects, they also dis- agree in some important particulars. They both first affect the anterior extremities of frogs, and both diminish respiration and cause hyperaesthesia during the latter stage of the poisoning process, although the supersensitive- ness is much more marked in theine than in caffeine. They differ in the following respects : Theine principally affects sensation, while caf- feine does not ; theine produces spontaneous spasms and convulsions, while caffeine does not until very late in the stage of poisoning ; theine impairs the nasal reflex early in the poisoning process, while caffeine does not, if at all, until the very last stage ; the lethal dose of theine is larger than that of caffeine. The differences in the action of these two l6 PHYSIOLOGICAL ACTION agents as here indicated will, I think, be suffi- cient to convince even the most skeptical that theine and caffeine can no longer be regarded as identical, so far as their physiological action on the frog is concerned. In order to show to myself, as well as to others, that there is a de- cided difference between the two preparations, and that I did not practice any unconscious self-deception, I frequently tested the contents of two numbered vials, one of which contained theine and the other caffeine, but which were only known to me by their numbers, and could, without difficulty, always designate the true nature of each specimen after testing its action on the frog. This is, certainly, a crucial ex- periment which demonstrates very clearly that the toxicological tests of experimental physi- ology are more accurate and delicate than those of physics and chemistry combined. The argument which has been advanced against my deductions that the theine and caffeine employed by me were probably not OF THEINE 17 chemically pure, must, I think, fall to the ground, when it is taken into consideration that precisely identical results were obtained from two separate manufactures of both alkaloids by Merck, of Darmstadt, against neither of which the charge of impurity can be brought. In the early part of my experimental review I did use preparations of both which were not altogether free from the coloring matter of the raw ma- terial, but they gave rise to the same differences as those which were brought out subsequently by the purer specimens. However, if the ob- jection of impurity be still urged, it devolves on those who make it to manufacture such specimens of both alkaloids which will satisfy their ideal of purity, and have them subjected to a proper test for the purpose of finding out whether they fail to give a differential physio- logical reaction. The power of theine to produce such decided and complete sensory paralysis in the lower animals led me to test its physiological prop- PHYSIOLOGICAL ACTION erties on the healthy human being, and, with this end in view, I introduced moderate, or probably small, doses of the drug hypoderm- ically in a nuijiber of instances, and noted the results. In the main, there was a general agreement in the symptoms which developed, and hence only one case, typical of the rest, will be given here. The drug was injected into the left fore- arm of an adult in good health, whose same arm, however, was fatigued by carrying a satchel to the railroad station on the previous morning. 1.40 p. M. Injected i grain of theine in left fore- arm, near elbow. 1.42. Fatigue in arm gone. 1.43. Diminution of sensibility in left forearm, especially around seat of injection. 1.46. Diminished sensibility extends as far as hand. 1.48. Some burning at seat of injection. 1.49. Touch impaired in tips of fingers of same hand. OF THEINE 19 1.5 1. Tingling in wrist and fingers. 1.52. No discernible influence on pupil. 1.54. Voluntary motion of arm and hand unim- paired. 1.56. Burning around seat of puncture gone. 2.02. No impairment of sensation above the elbow. 2.03. Slight shooting pains along the posterior part of left arm above elbow. 2.06. Sensibility of finger tips impaired. 2.08. Finger tips very dull. 2.1 1. In playing the piano, can move the fin- gers of left hand as well as those of right. 2.13. Mind perfectly clear. 2.30. Sensibility absolutely gone around seat of injection. 2.34. Finger and left hand feel as if " asleep." 2.44. Left hand numb. 2.55. No difference in temperature between two hands. 3.01. Finger tips very numb. 3.06. Feels somewhat sleepy. 20 PHYSIOLOGICAL ACTION 5.30. Sensibility still impaired, especially in fin- ger tips. Arm above elbow uninfluenced. 6.40. Sensation more normal in forearm. Fin- ger tips still feel numb. 8.00. Sensation entirely restored. Some red- ness and tenderness around seat of punc- ture. The physiological action of theine on man, as brought out in this as well as in a number of other observations under my care, may be summed up as follows : Dose from one-fifth to half a grain. Numbness of arm and hand below seat of injection — " a feeling as if the hand had been steeped in a solution of carbolic acid," as one of the subjects of experimentation expressed it. A feeling of coldness and an occasional disturbance of temperature in the member under its influence. A slight reduction in the pulse rate, and no intoxication of the brain. No im- pairment of motion. The anaesthesia shows itself in a very few minutes, and is much more marked in some individuals than in others. A OF THEINE 21 relief to the feeling of fatigue. The tempera- ture disturbance was not regular. Out of four cases in which the temperature was taken, it showed no difference in one, and in another one the uninjected hand was slightly higher (0.4° Fahr.) in temperature than the injected one. In two there was quite a marked fall in temperature — one 0.8° Fahr. and the other 1.2° Fahr. lower in the hand of the injected than in that of the uninjected arm. And, strange to say, the hand which showed the greatest de- pression in temperature experienced the least degree of anaesthesia. A certain feeling of coldness always accompanies the numbness produced by theine, yet, in my earlier observa- tions, I repeatedly failed to detect any ther- mometric differences. Dr. C. H. Castle, of Cincinnati, Ohio, was in- duced to test the action of theine by the appear- ance of my first article on this subject.^ The * The Therapeutic Action of Theine; a New Analgesic. Phila. Medical News ^ December 12th, 1885. 22 PHYSIOLOGICAL ACTION results of his experiments, which were both of a physiological and chemical nature, were read before the Cincinnati Medical Society, and pub- lished in The Cincinnati Lancet and Clinic for February 6th, 1886, and since they were made with pure theine, extracted by his own chemist, and because they add some hitherto unobserved features in the action of the drug, they are ex- tremely interesting and instructive. He made, in all, three physiological experiments on him- self, of which he says : — " The first time I injected one-sixth of a grain into my left forearm, immediately below the flexure of the elbow joint. I will not weary you with the details of the observations as made at intervals of a few minutes. The noticeable effect was remarkably rapid. An angry blush and swelling spread from the point of injection, but what looked like a most delicately ten- der spot was singularly devoid of sensation. It was not, nor did it become, totally anaesthetic, but in what appeared to be OF THEINE an inflamed area of sensibility was markedly dulled. Presently a numbness, such as we feel when a member is beginning to 'go to sleep,' from pressure upon its supplying nerves, stole over my wrist and hand. Little tinglings, scarcely noticeable had not one been on the watch for strange manifestations, came and went in various places. At no time was motility impaired. The temperature of the left hand, and I beg to call your attention to this point, was markedly lowered. The effects of the injection lasted about two hours. " The second injection was made under somewhat different circumstances. I had rather severely bruised my right hand, and the pain on pressure over the metacarpal bone was quite severe. I therefore injected one-third grain of theine subcutaneously over the ulnar nerve just below the elbow. ** The same phenomena were noticed as in the first use of the alkaloid — sensibility around the injection was markedly diminished, lower 24 PHYSIOLOGICAL ACTION down the forearm and in the wrist and hand less markedly so ; the right hand lost as much in temperature as had the left hand previously, but I am compelled to say that I was disap- pointed in the analgesic effect that I had expected. The extreme sensibility was dulled, to be sure, and my hand no longer hurt when I put it into my overcoat pocket, as it had be- fore, but any deep pressure instantly informed me that the nerves about the joint still resented the impact of a foreign body with the surface. " The third observation was made again upon the left arm ; this time one-half of a grain was used, and though an accident, perhaps, somewhat marred the experiment, some points were brought out more prominently. The in- jection, made for me by a friend, was a deep one — intermuscular — and the withdrawal of the needle was followed by a slight hemorrhage, sufficient to raise a conical subcutaneous tumor of a diameter of a one-cent piece. Instantly there was a deep-seated pain, probably due, I OF THEINE 25 thought, to extravasation from the wounded vessels into the intermuscular planes. Full ex- tension was impossible ; partial extension very painful ; the painful seats being deeply under the point of injection and the dorsal aspect of the metacarpo-phalangeal points. " As in former observations, sensibility was affected almost immediately, and in three minutes the left hand was blanched and al- most cold to the touch. My pulse was always full, strong, and but slightly more frequent than normal. Very soon peculiar constitutional disturbances appeared, and not entirely like those described in the standard works on ma- teria medica. I was excited and talkative, and so rapidly did I talk that I would soon exhaust a subject broached by others, and endeavor to introduce some natural descendant of the idea as a topic of conversation, apparently so far ahead of its proper sequence in a well-ordered train of thought as to appear like an interrup- tion with an irrelevant subject. Failing to 26 PHYSIOLOGICAL ACTION gain a hearing, as I frequently did, I would in- dulge in snatches of song or broken ejaculations which had a world of meaning in them then, but which, as I look back upon them now, seem utterly absurd. "Alternating with states of great bodily ac- tivity were spells almost of a fainting character. These were seven or eight in number, and beginning soon after the injection, gradually ceased after the lapse of six or seven hours." This vivid description of the effects of theine, as Dr. Castle observed them on himself, is very instructive, and in some respects new. The psychic disturbance which he experienced I have never observed, although I have admin- istered five times the quantity he employed ; and the only way in which I can account for his cerebral intoxication is on the score that the deep injections which he practiced chanced to in- troduce the theine directly into a blood vessel, and it was at once carried to the brain and pro- duced the hallucinations as described. This OF THEINE 27 is all the more probable because the central disturbance manifested itself directly after the injection, which, ordinarily, should not have appeared until in a later stage of the poisoning process. From these experiments, and from those which were made on the frog, I think the follow- ing conclusions may be legitimately drawn concerning the physiological action of theine on man : — 1. It has a special affinity for the nerves of sensation. 2. It produces anaesthesia when administered subcutaneously. 3. Its anaesthetic action is confined below the seat of its injection, /. PAIN OF Has been unable to walk or move his arms for three months, and on account of the pain in the back, arms and legs he is compelled to pass days and nights without sleep. Has well- marked constriction around the base of his chest and suffers from oedema and spasmodic contractions of both extremities. This patient received two and a half grains of theine every other day, in different spots along the spine, with the effect of giving him relief to his pain. This course was pursued for about four months, and while it did not ameliorate his general condi- tion, it gave him sleep, relieved the pain and contractions in the back and extremities, removed the thoracic constriction, and, on the whole, it made the patient feel more comfort- able than he was before. It is but fair to state here that, in another case of locomotor ataxia, the theine injections sig- nally failed to relieve the pain. This patient was, however, addicted to the protracted use of large doses of morphine, and the pain of which LOCOMOTOR ATAXIA 79 he complained was chiefly referred to the stomach, and, no doubt, partook of the nature of opium pain. This was promptly relieved by the subcutaneous administration of morphine. APPENDIX. Dr. Charles K. Mills, President of the Phila- delphia Neurological Society, made the following remarks on a paper entitled " Theine in Pain," which I had the pleasure of reading before that Society, De- cember 19th, 1887 [copied irova Jozirnal of Nervous Diseases^ January, 1888] : — "A few months ago I began the use of theine, or- dering it in nearly every case of neuralgia, superficial neuritis or lumbago that came to the Polyclinic service, and also using it at the Philadelphia Hospital. I have used the drug probably in about fifteen cases, but I have not had time to prepare notes of them for this meeting. I recall three cases of sciatica, two of which were of long standing. These cases were all m proved, but none of them were cured, by the use of theine alone. The pain was usually much relieved by the hypodermatic use of theine, but it would re- turn after a shorter or a longer time. In connection with the theine, I used galvanism to the nerve and muscles, and internally Donovan's solution, or iodide of potassium. Two of the cases of sciatica were cured under this conjoint treatment. 81 82 APPENDIX *' In a case of facial neuralgia, or neuritis, I used a hypodermic of theine in the face ; following this, the patient became pale, sick at the stomach, and seemed to be in a slightly dazed condition for a time. Whether this was due to the drug or simply to the slight oper- ation, I cannot say. The injection entirely relieved the pain for three days. The patient then returned, and another injection was given, without bad effect. In another facial case the patient was certainly re- lieved by theine, and, so far as I know, remained well. " I have used it in the back with great benefit in so-called myalgia, including under that term muscular rheumatism, and possibly true lumbar neuralgia. " I believe that theine is an analgesic ; that it re- lieves pain in cases of recent and superficial neuritis, or neuralgia. In chronic, painful nerve troubles, par- ticularly where the nerves are deeply situated, it seems to be simply a helping remedy, and sometimes fails." INDEX. A CTION. differential, between morphine and theine, 34, -^^ Action, differential, between theine and caffeine, 16. Action of theine confined below seat of injection, 35. Adjuvant treatment, 40. "D AKER, Dr. W. H., experience with theine, 50. ^ Bennett, Dr. G. D., experience with theine, 63. Botanical origin of theine, 9. /^^ASTLE, Dr. C. H., experiments with theine, 21. ^-^ Cerebral intoxication of theine, 25. Cervico-brachial neural2:ia, 62. Coffee and tea, gross effects of, 13. Coffee more powerful than tea, 14. Crucial differential test, 16. "T^EEP injections of theine not necessary, 29. -*-^ Dissimilarity of effects of theine and caffeine, 15. Dorsal or interscapular neuralgia, 61. Dose of theine, 30. TZTEELIXG of coldness produced by theine, 21. -*- Fegley, Dr. H. C, experience with theine, 46. Formula for hypodermatic use, 32. /^"'OVE, Dr. Geo. S., expeiience with theine, 54. ■jLJ ARRIS, Wm., manufactured theine and caffeine for -'■ -*■ author. 12. IDENTITY, supposed, of theine and caffeine, 13. -*• Importance of removing diathesis on which pain depends, 33- Intercostal neuralgia, 58. Iodide of potassium in sciatica, 51. " " " lumbago, 76. Irritation produced by hypodermatic injection of theine not prolonged, 31. T ETHAL dose of theine larger than of caffeine, 15. -'-^ Local action of theine, 34. Lumbago, 74. 83 84 INDEX A/TERCK'S theme reliable, 33. ^^^ Mills, Dr. Chas. K., experience with theine, 81. Morphine, general action of, 34. Musculo-rheumatic pain, 76. Myalgia, 72. TVJEURALGIA, definition of, 37. -'-^ " varieties of, 38. Neurasthenia, 69. Neuritis, 82. QCCI PIT AL neuralgia, 64. ^-^ Opium pains, 79. Origin and nature of neuralgia, 39. ■pAINFUL diseases, theine in, 70. ^ Pain of locomotor ataxia, 77. Physiological diflference between theine and caffeine, 15. Physiological test for theine, 16. Prompt action of theine, 30. "p EDUCTION of pulse by theine, 20. -*^ Rheumatic neuralgia, 65. CCIATICA, 39. *^ Seibert, Dr. J. L., experience with theine, 55. S , Dr., experience with theme, 48. Sensory paralysis produced by theine, 17. Spinal irritation, theine in, 67. 'T^ABLETS of theine for hypodermatic use, 32. -*• Tea as a beverage, 9. Tea, botanical origin of, 9. Temperature, influence of theine on, 21-23. Theine in pain of locomotor ataxia, 77. Theine, its chemical form.ula, 10. ** " solubility in water, 10. " " indiscriminate manufacture, 11. " " function is only as a pain reliever, 33. T TNRELIABILITY of ordinary commercial theine, 32. VyODDROP, Dr. H., experience with theine, 69. LIBRARY OF CONGRESS 022 216 059 5 \. f \^:'^^:m,^ ^. >-^^ U i\yy^^ .•'^VTi:^^-.