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Relief of pain following oral surgery
RELIEF
OF PAIN
FOLLOWING
Evaluation VICTOR
I-I. FRANK,
ORAL
SURGERY
of a New Medication D.D.S., PHILADELPHIA,
PA,
INCE earliest times the science of dentistry has been concerned with methods of avoiding or dealing with the sensation called pain. We know that, of all sensory end organs, pain receptors alone fail to become adapted to successive stimuli1 And we know that pain differs from other common sensations in that its perception can be modified by analgesic agentq2 Controlled studies on pain have shown that while the pain threshold in man is fairly uniform, the reaction thresho!d is extremely variable.“3 4 It would appear t,hat pain perception is a purely sensory phenomenon and that pain reaction is a psychological phenomenon. However, whether one is dealing with a patient’s perception of pain or with his reaction to it, he is entitled to relief. As dental practitioners we should, in so far as we are able, provide relief from pain for our patients. Such relief should be provided not only during surgical procedures, but in the postoperative period as well. Analgesics are most commonly used for postoperative pain relief. Their site of action is in the central nervous system. Although the nature of this action is unknown, it is believed that analgesics “cause a reduction in activity of centers concerned with the perception of pain, either by a direct threshold-raising action or by influences secondary to effects on mentation and mood.’ ‘j Among the various types of analgesics available are those that act primarily upon the threshold for pain perception such as aeetylsalicylic acid and phenacetin, and those that control reaction lo pain as well as raise the pain perception threshold, such as codeine and morphine. Slthough it is better known for its central nervous system stimulating effects, racemic amphet,amine sulfate has also been shown to possessanalgesic properties.6 Because they give a smoother, more efficient action, a combination of analgesic drugs from different chemical groups is considered to be more effective than a single substance.7 Combinations of acetylsalicylic acid and phenacetin have long been used for the relief of slight to moderate pain. When dealing with moderately severe pain, it is almost routine to give codeine, alone or in combination with other analgesics. Side effects, however, limit the use of codeine in ambulant patients. For some time we have used APC (aspirin-phenacetin-caffeine) tablets for the relief of pain in the postoperative period. Since the majority of patients experience only slight to moderate pain, this medication has proved satisfactory in a high percentage of cases. A smaller number of patients, however, particularly those in whom the procedure performed has resulted in severe or extensive tissue damage, experience pain of such character and intensity that APC proves ineffective. It would be desirable to fortify the medication with codeine for
S
1375
1376
VICTOR
H.
YRANK
such patients. But clinical trial has shown that when codeine is prescribed in amounts sufficient to give relief, patients feel depressed and become so lethargic and sleepy that they are unable to carry on their normal activities. Since oral surgery patients expect to remain ambulant, we have follnd the use of medic+ tions with soporific effects t,o be unsa.tisfact,ory. Recently it was learntd that a medication that combined two analgesics with an antidepressant” ~vould become available i.n a second form; codeine was to be added to the formula. Each table of t,he new medication+ supplies : acetylsalicylic acid, 2.5 gr.; phenacetin, 2.,5 gr.; codeine sulfate, l/d gr.; and Benzedrine,f 2.5 mg. Logically, such a combination should give effective relief from moderat,ely sever-e pain. Further, it should improve the patient’s mood and give him a sense of well-being. The influence of mood on reaction to pain is well recognized.4. 8 Because of dissatisfaction with medications previously used for the relief of moderately severe pain experienced in the postoperative period, this new medication was evaluated. The following report gives a summary of the material and methods used and of observations made in the course of this investigation.
Clinical
Evaluation
of the Medication
Patient&--Ninety-six patients, upon whom surgical procedures had been performed, were given Edrisal with codeine during the postoperative period. The group was made up of 61 female patients and 35 male patients. Ages ranged from 13 to 58, with the majority in the 20- to 30-pear age group. Procedures performed were as follows : Removalof impactedteeth
39
Molars Multiple molars Others Uncomplicated removal of teeth Removal of roots Removal of cysts Removal of infected teeth Removal of soft tissue Treatment of infection Removal of tooth with 6 roots
45 ti
s
10 7 7 6 4
2 7
Use of Medication.-The medication was given routinely only in difficult cases in which the amount of trauma indicated that moderately severe to severe pain was to be expected. Other patients who received the medication were those who returned complaining of severe pain that had not been relieved by APC. It is known that patients can be convinced by suggestion that a medication will reduce or eliminate pain.’ Because we wanted to determine the effects of this medication without the influence of suggestion, the subject of pain relief was not discussed with the patient. The receptionist merely handed him an envelope containing the medication as he was leaving the office. On the *Edrisal, +Edrlsal $Trademark Philadelphia.
a product of Smith, with codeine, a product name for racemic
Kline & French Laboratories, of Smith, Kline & French amphetamine sulfate. Smith,
Philadelphia. Laboratories, Philadelphia. Kline & French Laboratories,
RELIF3
OF
PAIN
FOLLOWING
ORAL
1377
SURGERY
envelope was typed, “After 2 hours, or when pain begins, Thereafter, take 1 or 2 tablets every 3 hours, or as necessary Do not take more than 6 tablets within 24 hours. ”
Relief
Obtained.-All
but 2 of the 96 patient,s stated that some relief was Classification by degree of relief was as follows:
given by the medication.
84 6 3 1” 2s
Complete Almost complete Moderate Slight None *Took
only
1 dose
take 2’ tablets. to relieve pain.
each.
Most of the pat.ients stated that relief was obtained in approximately thirty minutes, whether a l- or 2-tablet dose was taken. A few patienm reported that relief was obtained in ten to fifteen minutes and an occasional The patient stated that one hour elapsed before he was completely relieved. On an aversize of the dose did, however, appear to affect duration of relief. age, the l-tablet dose gave three to four hours’ relief while the 2-tablet dose was effective for three and one-ha,lf to six hours.
Number of Doses Taken--The patient was permitted to determine the frequency with which he would repeat dosage and whether he would take a l- or 2-tablet dose. Such flexibility of administration allowed for variation in intensity of: or individual reaction to, pain. Each patient who received the medication was requested to keep a record of the time each l- or 2-tablet dose was taken. We knew from past experience that the majority of such patients received so little relief from APC tablets that they took up to 6 doses daily for five to six days. It was hoped that analysis of the dosage data would serve as a, check on the patients’ statements regarding degree of relief given by the medication being evaluated. The average number of doses taken during the entire postoperative period was 3.8. Sixty-eight of the 96 patients took 1 to 4 doses each. Only 8 patients took more than 6 doses. Since the 3 patients who stated that little or no relief was given by the medication took only 1 dose each, figures used in Table I and Fig. 1 are based upon the 93 patients who were relieved. As shown in the table, very few patients required t,he medication beyond a three-day period. TABLE
I -
FEMALES 1 day
2 3 4 5 7 9
days days days days days days
MALES
;i
:i 19 9 -
8 1 1 1
TOTAL
%
93 65 27 2 1”
100 70 29 2 2
1
:
Fig. 1 shows the number of l- and 2-tablet doses taken each day by the 93 patients who obtained relief from the medication.
1378
VICTOR
II.
FRAXK
Two points of significance are shown by Fig. 1 and Table 1: (1) very few doses were taken after the third day; (2) after the first day, by far the greater uumber of patients considered the I-talblet dose to give sufficient relief. When contrasted with the duration of therapy and number of tablets taken by comparable groups of patients usin g APC. it, is apparent that, this medication is far more effective.
~Nuunbercf @
I-tablet doses
takev,
Numberof2-tobletdosestaken Fig.
1.
Observations.-Pain, as evidenced by the number of tablets taken per dose and by the number of doses taken, did not appear to be influenced by the amount of trauma produced by the procedure performed. Neither was there a correlation between the amount of trauma and the degree of relief given by the medication. These findings were not surprising in view of the wide variation in degree For example, a patient with of, or reaction to, pain experienced by patients. minimal trauma from the uncomplicated removal of a tooth returned six hours later complaining of agonizing pain. Another, with considerable trauma resulting from the removal of an impacted premolar and two other teeth, stated that only a moderate degree of pain ~v-as experienced. A single dose of the medication gave all of the pain control that was required. When the self-determined dosage data were broken down by sex, some interesting sidelights were noted: percentagewise, men took far more 2-tablet doses
RELIEF
than days, five, that took,
did women; of the 6 2 women took it for seven, and nine days, little or no relief was 2 were men.
OF
PAIN
FOLLOWING
ORAL
SURGERY
1379
patients who took the medication for more than three four and 1 for five days, while three men took it for respectively. Further, of the 3 patients who stated given by the single dose of the medication that they
Discussion Since the medication used in this study contained a powerful central nervous system stimulant, it was expected that a few patients would experience some Apparently the ingredients are degree of wakefulness or excess stimulation. so well balanced that none of these 96 patients noted such effects. Five patients did, however, state that the medication made them feel drowsy. One patient said that it interfered with regularity of his bowels; since he required t,he medication for less than twenty-four hours, t,his observation is questionable. It should be emphasized that this series of patients included only those who had, or might be expected to have, more than the average degree of pain. Further, they were not influenced by the suggestion that the medication would be of value. Although the medication was administered as a plain white tablet that looked like aspirin, and patient,s were not aware of its ingredients, many volunteered the information that not only did it give them more relief than any medication taken in the past., but also that it made them feel surprisingly well generally. Unless burdened by pain or rendered lethargic by medication, almost all patients are able, and prefer, to carry on their regular activities following oral surgery. This medication proved particularly suitable for use in such paGents. Despite the fact that their pain was moderately severe to severe in degree, over 93 per cent of these patients were maintained in a state of ease. Further, t,hey did not experience the depressive effects that, so often are a.ssociated with the administration of codeine. Over a period of twenty-nine years we have used a number of different, analgesics and combinations of analgesics to control postoperative pain. No one medication has, or probably will, prove completely effective in every case. But Edrisal with codeine h.as given a higher percentage of satisfact,ory results than any previously used medication. It is believed that the superior effecm demonst,rated by this medication were due to two factors: the combination of analgesics exerted a high degree of pain relief; the benzedrine component counteracted undesirable effects of the codeine and, in addition, favorably influenced mood so that patients were given a sense of energy and well-being. Thus they were less preoccupied with their sensat,ion of pain.
Summary 1. The sensation known as physical pain is believed to be the result of individual reaction to messages originating in certain nerve fiber end organs. Almost all patients suffer from some degree of pain following oral surgery. Relief should be provided for such pain. 2. A new medication supplying three time-proved analgesics and an effective antidepressant was evaluated in a group of 96 patients suffering from more than
1380
VICTOR
H.
FRANK
the average degree of postoperative pain. Each tahlet supplied : acct~lsalic~lio acid 2.5 gr.; phenacetin, 2.5 gr.; codciue sult:atc, I,!’ go”.; and hcnzedrine, 2.5 mg. 3. Most patient,s obtained relief in ihirt) minutcts; drwatiw ul’ relief varied from three to six hours. JIegrees of relief obtained 1)~ the 96 patients were as Pollows: complete, 84; almost complctc, 6; moderate, :i; slight, I ; none, 2. 4. IWiraq oi’ the medication was coi~cludcd to bc (111~to two factors : the combination of analgesics exerted a high degree of paiu relief; the bxrzedrine component antagonized letharg)- and tlepression. As a result, pain was effectiveI? controlled, a sense of well-being was engendered, and patients were enabled to carry on their normal activit,ies.
References 1. CJontrol
of Pain Stomatology
in
Dental (Appletonl
Practice: J. L.
A Symposium Conducted T.,
Editor).
Philadelphia,
by 1940,
the Academy of J.
B.
Lippincott
Company, p. 54; pp. 193.154. 2. Wolff,
H. G.. and Wolf: S. : Pain, Springfielt?. 194S, Charles C Thomas, Publisher, pp. 65-66. V. C.: The Mental and Physical Effects of Pain, Edinburgh, 1949, E. & S. Livingstone. Variations in Cutaneous ant1 Visceral Pain Sensitivity Chapman, W. P., and Jones, C. M.: in Normal Subjects, J. Clin. Investigation 23: Sl-91, 1949. Pain (Research publication, Assoc. Nerv. & Ment. Dis., vol. 23) ; Baltimore, 1943, Williams & Wilkins Company, p. 357. Burrill, D. Y., Go&xl, F. R., and Ity, h. C.: The Pain Threshold Raising Effects of Amphetamine, J. D. Res. 23: 337-344, 1944. Goodman, L., and Gilman, A.: The Pharmacological Ba.sis of Therapeutics, Sew York, 1941, The Macmillian Company, pp. 234, 244. Therapy of Pain, J. A. M. A. Fantus, B. : The Therapy of the Cook County Hospital: 103: 1939-1944, 1934.
3. Medvei, 4. 5. 6. 7. 8.
1800
PINE
ST.
OF PAIN
FOLLOWING
Evaluation VICTOR
I-I. FRANK,
ORAL
SURGERY
of a New Medication D.D.S., PHILADELPHIA,
PA,
INCE earliest times the science of dentistry has been concerned with methods of avoiding or dealing with the sensation called pain. We know that, of all sensory end organs, pain receptors alone fail to become adapted to successive stimuli1 And we know that pain differs from other common sensations in that its perception can be modified by analgesic agentq2 Controlled studies on pain have shown that while the pain threshold in man is fairly uniform, the reaction thresho!d is extremely variable.“3 4 It would appear t,hat pain perception is a purely sensory phenomenon and that pain reaction is a psychological phenomenon. However, whether one is dealing with a patient’s perception of pain or with his reaction to it, he is entitled to relief. As dental practitioners we should, in so far as we are able, provide relief from pain for our patients. Such relief should be provided not only during surgical procedures, but in the postoperative period as well. Analgesics are most commonly used for postoperative pain relief. Their site of action is in the central nervous system. Although the nature of this action is unknown, it is believed that analgesics “cause a reduction in activity of centers concerned with the perception of pain, either by a direct threshold-raising action or by influences secondary to effects on mentation and mood.’ ‘j Among the various types of analgesics available are those that act primarily upon the threshold for pain perception such as aeetylsalicylic acid and phenacetin, and those that control reaction lo pain as well as raise the pain perception threshold, such as codeine and morphine. Slthough it is better known for its central nervous system stimulating effects, racemic amphet,amine sulfate has also been shown to possessanalgesic properties.6 Because they give a smoother, more efficient action, a combination of analgesic drugs from different chemical groups is considered to be more effective than a single substance.7 Combinations of acetylsalicylic acid and phenacetin have long been used for the relief of slight to moderate pain. When dealing with moderately severe pain, it is almost routine to give codeine, alone or in combination with other analgesics. Side effects, however, limit the use of codeine in ambulant patients. For some time we have used APC (aspirin-phenacetin-caffeine) tablets for the relief of pain in the postoperative period. Since the majority of patients experience only slight to moderate pain, this medication has proved satisfactory in a high percentage of cases. A smaller number of patients, however, particularly those in whom the procedure performed has resulted in severe or extensive tissue damage, experience pain of such character and intensity that APC proves ineffective. It would be desirable to fortify the medication with codeine for
S
1375
1376
VICTOR
H.
YRANK
such patients. But clinical trial has shown that when codeine is prescribed in amounts sufficient to give relief, patients feel depressed and become so lethargic and sleepy that they are unable to carry on their normal activities. Since oral surgery patients expect to remain ambulant, we have follnd the use of medic+ tions with soporific effects t,o be unsa.tisfact,ory. Recently it was learntd that a medication that combined two analgesics with an antidepressant” ~vould become available i.n a second form; codeine was to be added to the formula. Each table of t,he new medication+ supplies : acetylsalicylic acid, 2.5 gr.; phenacetin, 2.,5 gr.; codeine sulfate, l/d gr.; and Benzedrine,f 2.5 mg. Logically, such a combination should give effective relief from moderat,ely sever-e pain. Further, it should improve the patient’s mood and give him a sense of well-being. The influence of mood on reaction to pain is well recognized.4. 8 Because of dissatisfaction with medications previously used for the relief of moderately severe pain experienced in the postoperative period, this new medication was evaluated. The following report gives a summary of the material and methods used and of observations made in the course of this investigation.
Clinical
Evaluation
of the Medication
Patient&--Ninety-six patients, upon whom surgical procedures had been performed, were given Edrisal with codeine during the postoperative period. The group was made up of 61 female patients and 35 male patients. Ages ranged from 13 to 58, with the majority in the 20- to 30-pear age group. Procedures performed were as follows : Removalof impactedteeth
39
Molars Multiple molars Others Uncomplicated removal of teeth Removal of roots Removal of cysts Removal of infected teeth Removal of soft tissue Treatment of infection Removal of tooth with 6 roots
45 ti
s
10 7 7 6 4
2 7
Use of Medication.-The medication was given routinely only in difficult cases in which the amount of trauma indicated that moderately severe to severe pain was to be expected. Other patients who received the medication were those who returned complaining of severe pain that had not been relieved by APC. It is known that patients can be convinced by suggestion that a medication will reduce or eliminate pain.’ Because we wanted to determine the effects of this medication without the influence of suggestion, the subject of pain relief was not discussed with the patient. The receptionist merely handed him an envelope containing the medication as he was leaving the office. On the *Edrisal, +Edrlsal $Trademark Philadelphia.
a product of Smith, with codeine, a product name for racemic
Kline & French Laboratories, of Smith, Kline & French amphetamine sulfate. Smith,
Philadelphia. Laboratories, Philadelphia. Kline & French Laboratories,
RELIF3
OF
PAIN
FOLLOWING
ORAL
1377
SURGERY
envelope was typed, “After 2 hours, or when pain begins, Thereafter, take 1 or 2 tablets every 3 hours, or as necessary Do not take more than 6 tablets within 24 hours. ”
Relief
Obtained.-All
but 2 of the 96 patient,s stated that some relief was Classification by degree of relief was as follows:
given by the medication.
84 6 3 1” 2s
Complete Almost complete Moderate Slight None *Took
only
1 dose
take 2’ tablets. to relieve pain.
each.
Most of the pat.ients stated that relief was obtained in approximately thirty minutes, whether a l- or 2-tablet dose was taken. A few patienm reported that relief was obtained in ten to fifteen minutes and an occasional The patient stated that one hour elapsed before he was completely relieved. On an aversize of the dose did, however, appear to affect duration of relief. age, the l-tablet dose gave three to four hours’ relief while the 2-tablet dose was effective for three and one-ha,lf to six hours.
Number of Doses Taken--The patient was permitted to determine the frequency with which he would repeat dosage and whether he would take a l- or 2-tablet dose. Such flexibility of administration allowed for variation in intensity of: or individual reaction to, pain. Each patient who received the medication was requested to keep a record of the time each l- or 2-tablet dose was taken. We knew from past experience that the majority of such patients received so little relief from APC tablets that they took up to 6 doses daily for five to six days. It was hoped that analysis of the dosage data would serve as a, check on the patients’ statements regarding degree of relief given by the medication being evaluated. The average number of doses taken during the entire postoperative period was 3.8. Sixty-eight of the 96 patients took 1 to 4 doses each. Only 8 patients took more than 6 doses. Since the 3 patients who stated that little or no relief was given by the medication took only 1 dose each, figures used in Table I and Fig. 1 are based upon the 93 patients who were relieved. As shown in the table, very few patients required t,he medication beyond a three-day period. TABLE
I -
FEMALES 1 day
2 3 4 5 7 9
days days days days days days
MALES
;i
:i 19 9 -
8 1 1 1
TOTAL
%
93 65 27 2 1”
100 70 29 2 2
1
:
Fig. 1 shows the number of l- and 2-tablet doses taken each day by the 93 patients who obtained relief from the medication.
1378
VICTOR
II.
FRAXK
Two points of significance are shown by Fig. 1 and Table 1: (1) very few doses were taken after the third day; (2) after the first day, by far the greater uumber of patients considered the I-talblet dose to give sufficient relief. When contrasted with the duration of therapy and number of tablets taken by comparable groups of patients usin g APC. it, is apparent that, this medication is far more effective.
~Nuunbercf @
I-tablet doses
takev,
Numberof2-tobletdosestaken Fig.
1.
Observations.-Pain, as evidenced by the number of tablets taken per dose and by the number of doses taken, did not appear to be influenced by the amount of trauma produced by the procedure performed. Neither was there a correlation between the amount of trauma and the degree of relief given by the medication. These findings were not surprising in view of the wide variation in degree For example, a patient with of, or reaction to, pain experienced by patients. minimal trauma from the uncomplicated removal of a tooth returned six hours later complaining of agonizing pain. Another, with considerable trauma resulting from the removal of an impacted premolar and two other teeth, stated that only a moderate degree of pain ~v-as experienced. A single dose of the medication gave all of the pain control that was required. When the self-determined dosage data were broken down by sex, some interesting sidelights were noted: percentagewise, men took far more 2-tablet doses
RELIEF
than days, five, that took,
did women; of the 6 2 women took it for seven, and nine days, little or no relief was 2 were men.
OF
PAIN
FOLLOWING
ORAL
SURGERY
1379
patients who took the medication for more than three four and 1 for five days, while three men took it for respectively. Further, of the 3 patients who stated given by the single dose of the medication that they
Discussion Since the medication used in this study contained a powerful central nervous system stimulant, it was expected that a few patients would experience some Apparently the ingredients are degree of wakefulness or excess stimulation. so well balanced that none of these 96 patients noted such effects. Five patients did, however, state that the medication made them feel drowsy. One patient said that it interfered with regularity of his bowels; since he required t,he medication for less than twenty-four hours, t,his observation is questionable. It should be emphasized that this series of patients included only those who had, or might be expected to have, more than the average degree of pain. Further, they were not influenced by the suggestion that the medication would be of value. Although the medication was administered as a plain white tablet that looked like aspirin, and patient,s were not aware of its ingredients, many volunteered the information that not only did it give them more relief than any medication taken in the past., but also that it made them feel surprisingly well generally. Unless burdened by pain or rendered lethargic by medication, almost all patients are able, and prefer, to carry on their regular activities following oral surgery. This medication proved particularly suitable for use in such paGents. Despite the fact that their pain was moderately severe to severe in degree, over 93 per cent of these patients were maintained in a state of ease. Further, t,hey did not experience the depressive effects that, so often are a.ssociated with the administration of codeine. Over a period of twenty-nine years we have used a number of different, analgesics and combinations of analgesics to control postoperative pain. No one medication has, or probably will, prove completely effective in every case. But Edrisal with codeine h.as given a higher percentage of satisfact,ory results than any previously used medication. It is believed that the superior effecm demonst,rated by this medication were due to two factors: the combination of analgesics exerted a high degree of pain relief; the benzedrine component counteracted undesirable effects of the codeine and, in addition, favorably influenced mood so that patients were given a sense of energy and well-being. Thus they were less preoccupied with their sensat,ion of pain.
Summary 1. The sensation known as physical pain is believed to be the result of individual reaction to messages originating in certain nerve fiber end organs. Almost all patients suffer from some degree of pain following oral surgery. Relief should be provided for such pain. 2. A new medication supplying three time-proved analgesics and an effective antidepressant was evaluated in a group of 96 patients suffering from more than
1380
VICTOR
H.
FRANK
the average degree of postoperative pain. Each tahlet supplied : acct~lsalic~lio acid 2.5 gr.; phenacetin, 2.5 gr.; codciue sult:atc, I,!’ go”.; and hcnzedrine, 2.5 mg. 3. Most patient,s obtained relief in ihirt) minutcts; drwatiw ul’ relief varied from three to six hours. JIegrees of relief obtained 1)~ the 96 patients were as Pollows: complete, 84; almost complctc, 6; moderate, :i; slight, I ; none, 2. 4. IWiraq oi’ the medication was coi~cludcd to bc (111~to two factors : the combination of analgesics exerted a high degree of paiu relief; the bxrzedrine component antagonized letharg)- and tlepression. As a result, pain was effectiveI? controlled, a sense of well-being was engendered, and patients were enabled to carry on their normal activit,ies.
References 1. CJontrol
of Pain Stomatology
in
Dental (Appletonl
Practice: J. L.
A Symposium Conducted T.,
Editor).
Philadelphia,
by 1940,
the Academy of J.
B.
Lippincott
Company, p. 54; pp. 193.154. 2. Wolff,
H. G.. and Wolf: S. : Pain, Springfielt?. 194S, Charles C Thomas, Publisher, pp. 65-66. V. C.: The Mental and Physical Effects of Pain, Edinburgh, 1949, E. & S. Livingstone. Variations in Cutaneous ant1 Visceral Pain Sensitivity Chapman, W. P., and Jones, C. M.: in Normal Subjects, J. Clin. Investigation 23: Sl-91, 1949. Pain (Research publication, Assoc. Nerv. & Ment. Dis., vol. 23) ; Baltimore, 1943, Williams & Wilkins Company, p. 357. Burrill, D. Y., Go&xl, F. R., and Ity, h. C.: The Pain Threshold Raising Effects of Amphetamine, J. D. Res. 23: 337-344, 1944. Goodman, L., and Gilman, A.: The Pharmacological Ba.sis of Therapeutics, Sew York, 1941, The Macmillian Company, pp. 234, 244. Therapy of Pain, J. A. M. A. Fantus, B. : The Therapy of the Cook County Hospital: 103: 1939-1944, 1934.
3. Medvei, 4. 5. 6. 7. 8.
1800
PINE
ST.