- Email: [email protected]
OPIATE ANTAGONISM FAILS TO REVERSE HYPNOTIC-INDUCED ANALGESIA
1355 decreased exocrine pancreatic and biliary secretions, the that endogenously excreted PP might serve such an in-vivo role was suggested. This hypothesis remains to be tested ; meantime we wish to note that substantial amounts of immunoreactive glucagon and insulin can also be found in human pancreatic exocrine secretions. In patients undergoing cannulation of the major pancreatic duct for diagnostic purposes, we found insulin levels in pancreatic juice ranging from 4 to 1155 U/ml and glucagon concentrations ranging from 192 to 1449 pg/ml. In pancreatic-duct-cannulated dogs, immunoreactive insulin levels rose significantly and glucagon levels dropped during glucose administration. The finding of islet-like peptides in pancreatic exocrine juice is not altogether surprising. Islet cells derive, it is believed, from exocrine ductular cells,9 and in cephalochordates, amphioxus, and mussels, which have no separate islet organ or exocrine pancreas, cells with immunohistochemical properties of insulin-secreting beta and glucagon-secreting alpha cells have been identified in the gastrointestinal mucosa. 10,11 Nevertheless, studies will have to be designed to determine the exact origin of these islet-like peptides in pancreatic juice and to determine what role they play in nutrient metabolism.
VOLUNTEER’S
causes
possibility
Departments of Medicine and Surgery, Loyola University Stritch School of Medicine, Maywood, Illinois 60153, U.S.A., and Research Service, V.A. Hospital,
Hines, Illinois
A. M. LAWRENCE R. A. PRINZ E. PALOYAN W. A. KOKAL
OPIATE ANTAGONISM FAILS TO REVERSE HYPNOTIC-INDUCED ANALGESIA
SIR,-Although the endogenous, opiate-like peptides (endorphins) have been implicated in the analgesic mechanism of various treatments, such as placebo,’ acupunctureand nitrous oxide3 their role in hypnotic analgesia is unknown. One single blind study4 indicated that naloxone, a specific opiate antagonist, at a dose of 4 mg intravenously, reversed hypnoticinduced analgesia. However, other reports5.6demonstrated that naloxone in doses of 0.4mg subcutaneously or 0.8-1 mg i.v. failed to alter the hypnotic-induced analgesia. Here, we report the failure of a much higher dose of naloxone (50 mg i.v.) to reduce or abolish hypnotic analgesia. The volunteer, a 22-year-old male, who was susceptible to hypnosis, gave informed consent to the study. He was instructed to rate the pain of the pricks of a 21-gauge needle to the back of his hand as 0 (no feeling), 1 (just touching), 2 (moderately painful pinprick), or 3 (severely painful pinprick). He was hypnotised, and glove analgesia was induced in his left hand. An i.v. injection of either 20 ml physiological saline or naloxone 50 mg in 20 ml water was given over a 10 min period before measurement of pain perception. Neither the volunteer nor the rating physician knew what was being injected. The same procedure was repeated the next day. Pain was rated by the patient in right and left hands every 3 min. The results (see table) indicate that naloxone dose not antagonise hypnotic-induced analgesia, suggesting that endorphins are probably not involved in this type of analgesia. This accords with some reports cited above, but is also consistent with the features of hypnotic-induced analgesia which are different from other types of analgesia in that it can be induced 9. Satake, K., Pairent, F. W., Romero, F. Surg. Gynec. Obstet. 1972, 134, 589. 10. Kataoka, K., Fujita, H. Arch. Histol. Jap. 1974, 36, 401. 11. Fritsch, H. A., VanNoorden, S., Pearse, A. G. Cell Tissue Res. 1976, 165, 365. 1. Levine, J. D., Gordon, N. C., Fields, H. L. Lancet, 1978, ii, 654. 2. Mayer, D. J., Price, D. D., Rafii, A., Barber, J. in Advances in Pain Research and Therapy vol. I: proceedings of First World Congress on Pain (edited by J. J. Bonica and D. Albe-Fessard); p. 751, New York, 1976. 3. Berkowitz, B. A., Ngai, S. H., Finck, A. D. Science, 1976, 194, 967 4. Stephenson, J. B. P. Lancet, 1978, ii, 991. 5. Goldstein, A., Hilgard, E. R. Proc. natn. Acad. Sci. 1975, 72, 2041. 6. Barber, J., Mayer, D.
Pain, 1977, 4, 41.
RATING OF PAIN UNDER HYPNOSIS WITH GLOVE
ANALGESIA IN THE LEFT HAND FOLLOWING ADMINSTRATION OF
NALOXONE OR PLACEBO
differentially in specific parts of the body, it can be turned off and on abruptly by suggestion (which is not concordant with the release of a substance), and it can remain effective for hours with no development of "tolerance", which is unlike the pattern seen with acupuncture or external opiate administration. The
same above arguments also apply to other mechanisms of analgesia involving the release of a substance, such as cholinomimetic agents (whose analgesic effects are also antagonised by naloxone).7 The mechanism of hypnotic-induced analgesia remains unknown, and could involve an entirely different psychophysiological or neurochemical mechanism. Research into the mechanism of hypnotic-induced analgesia is important, since it could provide insights into the neural mechanism underlying the hypnotic state itself.
Supported by Medical Research Service of the Veterans AdministraCenter, San Diego (MRIS 4576), N.I.M.H. grant 1 P50
tion Medical Tj’3rtQi
m
Department of Psychiatry, School of Medicine, University of California at San Diego, La Jolla, California 92093, U.S.A.
HENRY A. NASRALLAH THOMAS HOLLEY DAVID S. JANOWSKY
PERITONITIS IN PERITONEAL DIALYSIS
SIR,-Peritonitis is
a serious problem in chronic peritoneal The abdominal skin flora, the intestinal flora, and dialysis. contaminated dialysis fluid are generally considered the main sources of infection. 1.2 However, little is known about the rela-
7.
Pedigo, N. W., Dewey, W. L., Harris, L. S. J. Pharmac. exp. Ther. 1975, 193, 845. 1. Black, H. R., Finkelstein, F. O., Lee, R. V. Trans. Am. Soc. artif. intern. Organs, 1974, 20, 115. 2. Kolmos, H. J., Andersen, K. E. H. Scand. J. infect. Dis (in the press). CAUSATIVE MICROORGANISMS AND PROBABLE SOURCES OF PERITONITIS
VOLUNTEER’S
causes
possibility
Departments of Medicine and Surgery, Loyola University Stritch School of Medicine, Maywood, Illinois 60153, U.S.A., and Research Service, V.A. Hospital,
Hines, Illinois
A. M. LAWRENCE R. A. PRINZ E. PALOYAN W. A. KOKAL
OPIATE ANTAGONISM FAILS TO REVERSE HYPNOTIC-INDUCED ANALGESIA
SIR,-Although the endogenous, opiate-like peptides (endorphins) have been implicated in the analgesic mechanism of various treatments, such as placebo,’ acupunctureand nitrous oxide3 their role in hypnotic analgesia is unknown. One single blind study4 indicated that naloxone, a specific opiate antagonist, at a dose of 4 mg intravenously, reversed hypnoticinduced analgesia. However, other reports5.6demonstrated that naloxone in doses of 0.4mg subcutaneously or 0.8-1 mg i.v. failed to alter the hypnotic-induced analgesia. Here, we report the failure of a much higher dose of naloxone (50 mg i.v.) to reduce or abolish hypnotic analgesia. The volunteer, a 22-year-old male, who was susceptible to hypnosis, gave informed consent to the study. He was instructed to rate the pain of the pricks of a 21-gauge needle to the back of his hand as 0 (no feeling), 1 (just touching), 2 (moderately painful pinprick), or 3 (severely painful pinprick). He was hypnotised, and glove analgesia was induced in his left hand. An i.v. injection of either 20 ml physiological saline or naloxone 50 mg in 20 ml water was given over a 10 min period before measurement of pain perception. Neither the volunteer nor the rating physician knew what was being injected. The same procedure was repeated the next day. Pain was rated by the patient in right and left hands every 3 min. The results (see table) indicate that naloxone dose not antagonise hypnotic-induced analgesia, suggesting that endorphins are probably not involved in this type of analgesia. This accords with some reports cited above, but is also consistent with the features of hypnotic-induced analgesia which are different from other types of analgesia in that it can be induced 9. Satake, K., Pairent, F. W., Romero, F. Surg. Gynec. Obstet. 1972, 134, 589. 10. Kataoka, K., Fujita, H. Arch. Histol. Jap. 1974, 36, 401. 11. Fritsch, H. A., VanNoorden, S., Pearse, A. G. Cell Tissue Res. 1976, 165, 365. 1. Levine, J. D., Gordon, N. C., Fields, H. L. Lancet, 1978, ii, 654. 2. Mayer, D. J., Price, D. D., Rafii, A., Barber, J. in Advances in Pain Research and Therapy vol. I: proceedings of First World Congress on Pain (edited by J. J. Bonica and D. Albe-Fessard); p. 751, New York, 1976. 3. Berkowitz, B. A., Ngai, S. H., Finck, A. D. Science, 1976, 194, 967 4. Stephenson, J. B. P. Lancet, 1978, ii, 991. 5. Goldstein, A., Hilgard, E. R. Proc. natn. Acad. Sci. 1975, 72, 2041. 6. Barber, J., Mayer, D.
Pain, 1977, 4, 41.
RATING OF PAIN UNDER HYPNOSIS WITH GLOVE
ANALGESIA IN THE LEFT HAND FOLLOWING ADMINSTRATION OF
NALOXONE OR PLACEBO
differentially in specific parts of the body, it can be turned off and on abruptly by suggestion (which is not concordant with the release of a substance), and it can remain effective for hours with no development of "tolerance", which is unlike the pattern seen with acupuncture or external opiate administration. The
same above arguments also apply to other mechanisms of analgesia involving the release of a substance, such as cholinomimetic agents (whose analgesic effects are also antagonised by naloxone).7 The mechanism of hypnotic-induced analgesia remains unknown, and could involve an entirely different psychophysiological or neurochemical mechanism. Research into the mechanism of hypnotic-induced analgesia is important, since it could provide insights into the neural mechanism underlying the hypnotic state itself.
Supported by Medical Research Service of the Veterans AdministraCenter, San Diego (MRIS 4576), N.I.M.H. grant 1 P50
tion Medical Tj’3rtQi
m
Department of Psychiatry, School of Medicine, University of California at San Diego, La Jolla, California 92093, U.S.A.
HENRY A. NASRALLAH THOMAS HOLLEY DAVID S. JANOWSKY
PERITONITIS IN PERITONEAL DIALYSIS
SIR,-Peritonitis is
a serious problem in chronic peritoneal The abdominal skin flora, the intestinal flora, and dialysis. contaminated dialysis fluid are generally considered the main sources of infection. 1.2 However, little is known about the rela-
7.
Pedigo, N. W., Dewey, W. L., Harris, L. S. J. Pharmac. exp. Ther. 1975, 193, 845. 1. Black, H. R., Finkelstein, F. O., Lee, R. V. Trans. Am. Soc. artif. intern. Organs, 1974, 20, 115. 2. Kolmos, H. J., Andersen, K. E. H. Scand. J. infect. Dis (in the press). CAUSATIVE MICROORGANISMS AND PROBABLE SOURCES OF PERITONITIS