Perceptual and Motor Skills, 1979, 48, 687-690. @ Perceptual and Motor Skills 1979 PAIN THRESHOLDS I N RATS DURING RECOVERY FROM REM SLEEP DEPRIVATION ROBERT A. HICKS, DAVID D. COLEMAN, FELICE FERRANTE, MANIK SAHATJIAN, AND JAMES HAWKINS Sun Jose State University Summary.-Using 30 Sprague-Dawley female rats, threshold to pain was measured over the course of recovery from REM sleep deprivation. Relative to the untreated controls and to their own pretreatment thresholds, the REM-deprived animals showed significantly reduced pain thresholds which were still evident 96 hours after the termination of the REM deprivation. Possible implications of these data for research with analgesic drugs were noted. In a recent study Hicks and his colleagues (Hicks, Moore, Findley, Hirshfield, & Humphrey, 1978) reported reduced pain thresholds in rats for at least a 24-ht. period subsequent to the termination of REM sleep deprivation. In that paper, they speculated that REMd might produce reductions in pain threshold that extended well beyond the time, i.e., a 24-hr. period, considered in that study. The purpose of this research was twofold, to serve as a replication of the Hicks, ec al. ( 1978) study and to extend the post-REMd testing to 96 hr. so the possibility of relatively long-term REMd effects on pain threshold could be checked. Our animals were 30 Sprague-Dawley female rats that were 45 days old (mean weight = 158 gm.) at the time of the pretest. These animals were divided into two groups, i.e., a four-day small platform REMd group, and an untreated control group. The control group was further divided into two groups, i.e., a dry control ( n = 7 ) and a wet large-platform control ( n = 8). The large and small platform diameters were 16.5 and 6 cm., respectively. REMd was achieved using a modification (see Hicks & Moore, 1978, for a complete description) of the water-tank method (Jouvet, Vimont, Delorme, 8: Jouvet, 1964) and is identical to the method used by Hicks, et al. (1978). All the animals spent the same amount of time in confinement in the REMd apparatus and the conuols served as checks on the effects of confinement in a novel environment and exposure to a wet environment which are inescapable concomitants of the water-tank method. The procedure used to measure sensitivity to pain was similar to the one used by Paalzow and Paalzow ( 1975 ) . Using this procedure, first a pre-experimental pain threshold was established for each animal. To do this the animal was restrained and electrodes were attached to the upper part of the tail. hen using the dial settings on a Grason-Stadler (Model 700) Shock Generator as intervals, an ascending series of .5-sec. stimulations was run until the animal
PAIN, REM SLEEP DEPRIVATION
689
REMd reduces threshold to pain and that this reduction in threshold persists well beyond the termination of REMd. In concluding, we should like to call attention to certain general implications that these data may have for pain research. Some analgesic drugs have been shown to have selective effects on REM sleep. For example, Kay (1975) demonstrated that during chronic administration of morphine REM sleep time persistently decreased. That is, the chronic use of this analgesic produced REMd. Thus, the tolerances (and/or the need to increase therapeutic dosages) which occur with the chronic use of some analgesics may be mediated, in part, by REMd-induced reductions in pain threshold. In an earlier study, Hicks, Paulus, and Johnson (1973) reported that REMd increased threshold to (painful) electric shock. This finding is not conuadictory to the data presented here, but rather is further evidence for the importance of establishing the relationship between analgesic drugs and REM sleep. T o explain, Hicks, et al. ( 1973) used Evans' ( 1961) "flinch-jump" technique to establish threshold. This response has been used (e.g., see Winter, 1965) as a method of measuring the analgesic power of drugs. This method seems to be a poor choice if the drug in question produces REMd, in that the Evans method requires the animal to learn a response (jumping) to terminate the painful shock, and it is a well-documented fact (e.g., Greenberg & Pearlman, 1974) that REMd interferes with this form of learning. That is, in this study the response used to measure pain sensitivity was probably inappropriate because REMd may have interfered with these animals' ability to acquire the response and, as a consequence, masked their actual pain thresholds. Hence the increases in pain threshold thar Hicks, et al. (1973) observed as a function of REMd were probably the result of a treatment X task confounding rather than a REMd-induced decrease in sensitivity to painful stimulation. It would seem prudent for researchers interested in studying the analgesic effects of drugs to consider first the effects that these drugs might have on REM sleep. REFERENCES
EVANS,W. 0. A new technique for the investigation of some analgesic drugs on a reflexive behavior in the rat.
I'~vchopharraco~ogia,1961, 2, 318-325.
GREENBERG, R.. & PEARLMAN, C. Cutting the REM nerve: an approach to the adaptive
role of REM sleep. Perspectives i n Biology and Medicine, 1974, 17, 513-521. HICKS,R. A., & MOORE,J. D. REM sleep deprivation diminishes fear in rats. Physiology and Behaoior, 1979, in press. HICKS,R. A., MOORE,J. D., FINDI-EY, P., H~RSHFIELD, C., & HUMPHREY, V. REM sleep deprivation and pain thresholds in rats. Perceptual and Motor Skills, 1978, 47, 848-850. HICKS,R. A., PAULUS.M. J.. & JOHNSON, J. C. Effect of REM sleep deprivation on electric shock threshold in rats. Psychologicd Reports, 1973, 32, 1242. J o w ~ r D., , VIMONT, P., DELORME, F., & JOUVET. M. Etude de la privation sCleccive de la phase paradoxal de sommeil chez 1e chat. Comptes R s n d t ~ sd e la Sociitd d e Biologie (Paris), 1964, 158, 756-759.
690
R. A. HICKS, ET AL.
KAY, D. C. Human sleep during chronic morphine intoxication. Psychopharmacologia, 1975, 44, 117-124. PAALZOW,G., & PAALZOW,L. Morphine-induced inhibition of different pain responses in relation to the regional turnover of rat brain noradrenaline and dopamine. Psychopharmacologia, 1975, 45, 9-20. WINTER,C. A. The physiology and pharmacology of pain and its relief. In G. deStevens (Ed.), Anulgetics. New York: Academic Press, 1965. Pp. 9-74.
Accepted March 30, 1979.
PAIN, REM SLEEP DEPRIVATION
689
REMd reduces threshold to pain and that this reduction in threshold persists well beyond the termination of REMd. In concluding, we should like to call attention to certain general implications that these data may have for pain research. Some analgesic drugs have been shown to have selective effects on REM sleep. For example, Kay (1975) demonstrated that during chronic administration of morphine REM sleep time persistently decreased. That is, the chronic use of this analgesic produced REMd. Thus, the tolerances (and/or the need to increase therapeutic dosages) which occur with the chronic use of some analgesics may be mediated, in part, by REMd-induced reductions in pain threshold. In an earlier study, Hicks, Paulus, and Johnson (1973) reported that REMd increased threshold to (painful) electric shock. This finding is not conuadictory to the data presented here, but rather is further evidence for the importance of establishing the relationship between analgesic drugs and REM sleep. T o explain, Hicks, et al. ( 1973) used Evans' ( 1961) "flinch-jump" technique to establish threshold. This response has been used (e.g., see Winter, 1965) as a method of measuring the analgesic power of drugs. This method seems to be a poor choice if the drug in question produces REMd, in that the Evans method requires the animal to learn a response (jumping) to terminate the painful shock, and it is a well-documented fact (e.g., Greenberg & Pearlman, 1974) that REMd interferes with this form of learning. That is, in this study the response used to measure pain sensitivity was probably inappropriate because REMd may have interfered with these animals' ability to acquire the response and, as a consequence, masked their actual pain thresholds. Hence the increases in pain threshold thar Hicks, et al. (1973) observed as a function of REMd were probably the result of a treatment X task confounding rather than a REMd-induced decrease in sensitivity to painful stimulation. It would seem prudent for researchers interested in studying the analgesic effects of drugs to consider first the effects that these drugs might have on REM sleep. REFERENCES
EVANS,W. 0. A new technique for the investigation of some analgesic drugs on a reflexive behavior in the rat.
I'~vchopharraco~ogia,1961, 2, 318-325.
GREENBERG, R.. & PEARLMAN, C. Cutting the REM nerve: an approach to the adaptive
role of REM sleep. Perspectives i n Biology and Medicine, 1974, 17, 513-521. HICKS,R. A., & MOORE,J. D. REM sleep deprivation diminishes fear in rats. Physiology and Behaoior, 1979, in press. HICKS,R. A., MOORE,J. D., FINDI-EY, P., H~RSHFIELD, C., & HUMPHREY, V. REM sleep deprivation and pain thresholds in rats. Perceptual and Motor Skills, 1978, 47, 848-850. HICKS,R. A., PAULUS.M. J.. & JOHNSON, J. C. Effect of REM sleep deprivation on electric shock threshold in rats. Psychologicd Reports, 1973, 32, 1242. J o w ~ r D., , VIMONT, P., DELORME, F., & JOUVET. M. Etude de la privation sCleccive de la phase paradoxal de sommeil chez 1e chat. Comptes R s n d t ~ sd e la Sociitd d e Biologie (Paris), 1964, 158, 756-759.
690
R. A. HICKS, ET AL.
KAY, D. C. Human sleep during chronic morphine intoxication. Psychopharmacologia, 1975, 44, 117-124. PAALZOW,G., & PAALZOW,L. Morphine-induced inhibition of different pain responses in relation to the regional turnover of rat brain noradrenaline and dopamine. Psychopharmacologia, 1975, 45, 9-20. WINTER,C. A. The physiology and pharmacology of pain and its relief. In G. deStevens (Ed.), Anulgetics. New York: Academic Press, 1965. Pp. 9-74.
Accepted March 30, 1979.
