Abstract
The present experiment investigated the possibility that endogenous opioids attenuate aversive experience in humans. Two experimental pain procedures—cold pressor pain, and ischemic pain produced by the submaximal effort tourniquet technique—were administered on each of 2 consecutive experimental days. Seven subjects received double-blind infusions of the opiate antagonist naloxone on Day 1 and saline on Day 2; for seven other subjects, the order was reversed. Based on earlier studies of exogenous opiate analgesics, the present experiment was designed to maximize subject anxiety and the “disturbingness” of the ischemic pain. Under these conditions, opiate receptor blockade significantly affected ratings and tolerance times for ischemic pain, anxiety, and mood. These results contrast with those of recent studies in which naloxone effects on experimental pain in humans were subtle or indiscernible, and suggest that psychological factors will have to be controlled and studied in the investigation of physiological bases of pain and other psychological states.
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Rozin, P., Ebert, L., & Schull, J. The liking for chili pepper: A temporal analysis of the hedonic response. Manuscript submitted for publication.
References
Adler, R., & Lomazzi, F. Mild analgesics evaluated with the submaximum effort tourniquet technique. Psychopharmacologia, 1974, 38, 351–362.
Akil, H., Mayer, D. J., & Liebeskind, J. C. Antagonism of stimulation-produced analgesia by naloxone, a narcotic antagonist. Science, 1976, 189, 961–962.
Akil, H., Richardson, D. E., Hughes, J., & Barchas, J. D. Enkephalin-like material elevated in ventricular cerebrospinal fluid of pain patients after analgetic focal stimulation. Science, 1978, 201, 463–465.
Amir, S., & Amit, Z. The pituitary gland mediates acute and chronic pain responsiveness in stressed and non-stressed rats. Life Sciences, 1979, 24, 439–448.
Amir, S., & Amit, Z. Endogenous opioid ligands may mediate stress-induced changes in the affective properties of pain behavior in rats. Life Sciences, 1978, 23, 1143–1152.
Beecher, H. K. Measurement of subjective responses. New York: Oxford University Press, 1959.
Bolles, R. C., & Fanselow, M. S. A perceptual-defensive-recuperative model of fear and pain. Behavioral and Brain Sciences, 1980, 3, 121–131.
Buchsbaum, M. D., Davis, G. C., & Bunney, W. E., Jr. Naloxone alters pain perception and somatosensory evoked potentials in normal subjects. Nature, 1977, 270, 620–622.
Chapman, C. R., & Feather, W. Effects of diazepam on human pain tolerance and pain sensitivity. Psychosomatic Medicine, 1973, 35, 330–339.
Davis, G. C., Buchsbaum, M. D., & Bunney, W. F., Jr. Naloxone decreases diurnal variation in pain sensitivity and somatosensory evoked potentials. Life Sciences, 1978, 23, 1449–1460.
Davis, M. Morphine and naloxone: Effects on conditioned fear as measured with the potentiated startle paradigm. European Journal of Pharmacology, 1979, 54, 341–347.
El-Sobky, A., Dostrovsky, J. O., & Wall, P. D. Lack of effect of naloxone on pain perception in humans. Nature, 1976, 263, 783–784.
Fanselow, M. S. Naloxone and Pavlovian fear conditioning. Learning and Motivation, in press.
Fanselow, M. S., & Bolles, R. C. Naloxone and shock-elicited freezing in the rat. Journal of Comparative and Physiological Psychology, 1979, 93, 736–744.
Frid, M., Singer, G., & Rana, C. Interactions between personal expectations and naloxone: Effects on tolerance to ischemic pain. Psychopharmacology, 1979, 65, 225–231.
A. Goldstein, & Grevert, P. Placebo analgesia, endorphins, and naloxone. Lancet, 1978, 654, 1385.
Gracely, R. H., McGrath, P., & Dubner, R. Validity and sensitivity of ratio scales of sensory and affective pain descriptors: Manipulation of affect by diazepam. Pain, 1978, 5, 19–29.
Gracely, R. H., Dubner, R., & McGrath, P. A. Narcotic analgesia: Fentanyl reduces the intensity but not the unpleasantness of painful tooth pulp sensation. Science, 1979, 203, 1261–1263.
Grevert, P., & Goldstein, A. Effects of naloxone on experimentally induced ischemic pain and on mood in humans. Proceedings of the National Academy of Science U.S.A., 1977, 74, 1291–1294.
Grevert, P., & Goldstein, A. Endorphins: Naloxone fails to alter experimental pain or mood in humans. Science, 1978, 199, 1093–1095.
Hardy, J. D., Wolff, H. G., & Goodell, H. Pain sensations and reactions. Baltimore: Williams and Wilkins, 1952.
Hill, H. E., Belleville, R. E., & Wikler, A. Studies on anxiety associated with anticipation of pain. Archives of Neurological Psychiatry, 1955, 73, 602.
Hill, H. E., Kornetsky, C. H., Flanary, H. G., & Wikler, A. Effects of anxiety and morphine on discrimination of painful stimuli. Federation Proceedings, 1951, 10, 309.
Hill, H. E., Kornetsky, C. H., Flanary, H. G., & Wikler, A. Studies on anxiety associated with anticipation of pain: I. Effect of morphine. AMA Archives of Neurology and Psychiatry, 1952, 67, 612–619. (a)
Hill, H. E., Kornetsky, C. H., Flanary, H. G., & Wikler, A. Effects of anxiety and morphine on discrimination of intensities of painful stimuli. Journal of Clinical Investigation, 1952, 31, 473–480. (b)
Hosobuchi, Y., Adams, J. E., & Linchitz, R. Pain relief by electrical stimulation of the central gray matter in humans and its reversal by naloxone. Science, 1977, 197, 183–185.
Johnson, J. E. Effects of accurate expectations about sensations on the sensations on the sensory and distress components of pain. Journal of Personality and Social Psychology, 1973, 27, 261–275.
Lasagna, L. Naloxone hyperalgesia in post operative patients. Proceedings of the Royal Society of Medicine, 1965, 58, 978–983.
Levine, J. D., Gordon, N. C., Jones, R. T., & Fields, H. L. The narcotic antagonist naloxone enhances clinical pain. Nature, 1978, 272, 826–827.
Maier, S. F., Drugan, R., Grau, J. W., Hyson, R., MacLennan, J. A., Moye, T., Madden, J., IV, & Barchas, J. D. Learned helplessness, pain inhibition, and the endogenous opiates. In M. D. Zeiler & P. Harzem (Eds.), Advances in analysis of behavior (Vol. 4). New York: Wiley, in press.
Mansky, P. A. Opiates: Human psychopharmacology. In L. L. Iversen, S. D. Iversen, & S. H. Snyder (Eds.), Handbook of psychopharmacology (Vol. 12): Drugs of abuse. New York: Plenum, 1978.
Meyer, F. P., Greksch, G., & Walther, H. Effectiveness of analgesics evaluated with the tourniquet technique. International Journal of Clinical Pharmacology, 1978, 16, 229–234.
Parry, W. L. The evaluation of analgesic drugs: The case for experimental methods. Anesthesia, 1979, 34, 468–475.
Riley, A. L., Zellner, D. A., & Duncan, H. J. The role of endorphins in animal learning and behavior. Neuroscience and Biobehavioral Reviews, 1980, 4, 69–76.
Roth, K. A., Katz, R. J., Schmaltz, K., & Sibel, M. Reduced behavioral activity due to opiate blockade: Relations to stress. International Journal of Neuroscience, 1981, 12, 59–62.
Schull, J. A conditioned opponent theory of Pavlovian conditioning and habituation. In G. Bower (Ed.), The psychology of learning and motivation. New York: Academic Press, 1979.
Schull, J. Pain, pleasure, and the effects of opiate receptor blockade in humans. (Doctoral dissertation, University of Pennsylvania, 1980). Dissertation Abstracts International, 1981, 41, 4300B. (University Microfilms No. 8107798)
Sherman, J. E., & Liebeskind, J. C. An endorphinergic, centrifugal substrate of pain modulation: Recent findings, current concepts and complexities. In J. J. Bonica (Ed.), Pain. New York: Raven Press, 1980.
Smith, G. M., Lowenstein, E., Hubbard, J. H., & Beecher, H. K. Experimental pain produced by the submaximum effort tourniquet technique: Further evidence of validity. Journal of Pharmacology and Experimental Therapeutics, 1968, 163, 468–474.
Snyder, S. H. Brain peptides as neurotransmitters. Science, 1980, 209, 976–983.
Sternbach, R. Pain: A psychophysiological analysis. New York: Academic Press, 1968.
Volavka, J., Bauman, J., Pevnick, J., Reber, D., James, B., & Cho, D. Short-term hormonal effects of naloxone in man. Psychoneuroendocrinology, 1980, 5, 225–234.
Von Graffenreid, B., Adler, R., Abt, K., Nuesch, E., & Spiegel, R. The influence of anxiety and pain sensitivity on experimental pain in man. Pain, 1978, 4, 253–263.
Willer, J. C., Dehen, H., & Cambier, J. Stress-induced analgesia in humans: Endogenous opioids and naloxone-reversible depression of pain reflexes. Science, 1981, 212, 689–691.
Wolff, B. B. Behavioral measurement of human pain. In R. A. Sternbach (Ed.), The psychology of pain. New York: Raven Press, 1978.
Wolff, B. B., Kantor, T. G., Murray, M. D., Jarvick, M. E., & Laska, E. Response of experimental pain to analgesic drugs: 1. Morphine, aspirin and placebo. Clinical Pharmacology and Therapeutics, 1966, 7, 224–238.
Wolff, H. G., Hardy, J. D., & Goodell, H. Studies on pain: Measurement of the effect of morphine, codeine and other opiates on the pain threshold and an analysis of their relation to the pain experience. Journal of Clinical Investigation, 1940, 19, 659–680.
Woolf, C. J. Transcutaneous electrical nerve stimulation and the reaction to experimental pain in human subjects. Pain, 1979, 7, 115–127.
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This study was conducted in the laboratories of the Drug Dependence Treatment and Research Service of the Philadelphia VA Medical Center, and was supported by USPHS Grants DA00586 and DA01218 and a VA Medical Research Grant to Charles O’Brien, by NSF Grant BNS 76-80108 to Paul Rozin, and by an NIH predoctoral fellowship, 5-F31-DA05132-02, to Jonathan Schull. For their assistance at various stages in this research project, we thank Doris Battle, Robert Greenstein, PriscillaGrevert, Ralph Lyons, Anthony Martinez, Sam Opaku, Martin Orne, Susan Ray, Anita Roselle, Paul Rozin, Richard Solomon, Joseph Ternes, S. Wallenstein, and George Woody.
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Schull, J., Kaplan, H. & O’Brien, C.P. Naloxone can alter experimental pain and mood in humans. Psychobiology 9, 245–250 (1981). https://doi.org/10.3758/BF03326970
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DOI: https://doi.org/10.3758/BF03326970