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Diurnal rhythms in nociceptive thresholds of rats
Physiology & Behavior, Vol. 23, pp. 419-420. PergamonPress and Brain Research Publ., 1979.Printed in the U.S.A.
Diurnal Rhythms in Nociceptive Thresholds of Rats J. P E T E R R O S E N F E L D
A N D P E T E R E. R I C E
D e p a r t m e n t s o f Psychiatry and Psychology N o r t h w e s t e r n University Evanston-Chicago, IL R e c e i v e d 10 F e b r u a r y 1979 ROSENFELD, J. P. AND P. E. RICE. Diurnal rhythms in nociceptive thresholds of rats. PHYSIOL. BEHAV. 23: (2) 419-420, 1979.--Paw lick, tail flick, and other nociceptive reaction latencies were observed in rats to be longer in the evening than in the daytime, suggesting an endogenous opiate mediated decrease in pain sensitivity in the evening in comparison with the daytime. Naloxone
Endorphin
Enkephalin
Nociception
F R E D E R I C K S O N et al. [1] reviewed and helped resolve the controversy over the direct (hyperalgesic) action of naloxone by noting a diurnal rhythm in nociceptive sensiti~;ity of mice: If naloxone's opiate antagonism is mediated by opiate receptor blockage, the endogenous opiate action should also be subject to block, resulting in direct hyperalgesic effects of naloxone. If, however, endogenous opioid levels follow a diurnal rhythm such that during morning and afternoon hours (when most studies are done) the nociceptive thresholds are maximally depressed, a further depression by naloxone might go undetected. Frederickson et al. [1] noted a diurnal rhythm in hot-plate jump latency but not in pawlick latency in mice. The present study was undertaken to see if diurnal phenomena were observable in rats. Three nociceptive latencies were observed: (1) paw-lick latency (any paw) and (2) latency to nociceptive reaction [2] on a 49°C hotplate, and (3) tail flick latency. In the paw lick test, animals are placed on a 49°C hotplate and a stopwatch is started. It is stopped when any paw is licked in response to the nociceptive heat level being reached. The second latency involves an orientation response or a flinch/jump or a sudden scampering escape attempt, whichever comes first. In the tail flick test, a beam of intense light is focused on the tip of the rat's tail. A stopwatch is started when the light is turned on and stopped when the tail is flicked in response; this also turns off the light. Twenty male albino rats (400-450 g) were tested on the hot plate measures 4 times a day for 7 days each. A subsample of 9 of these was given tail-flick testing also. Testing times were 11 a.m., 4 p.m., 7 p.m. and 11 p.m.. The rats were housed on a lighting schedule which had lights on from 8 a.m. to 8 p.m. and off otherwise. Food and water were available ad lib. Means over the 7 days were determined for each of the 4 test times for each rat, and then the two earlier times and the two later times were separately averaged within rats to yield one early and one late test latency. The results are given in Table 1 in terms of
Diurnal
Pain
mean -4- standard deviation. Within-subject (correlated), two-tailed t-tests were done on each pair of means in the 3 rows above. The significant t-values for the 3 rows were 2.69 (p<0.02), 2.27 (p<0.05), and 2.74 (p<0.05), respectively. The results in rats agree with the earlier results of Frederickson et al. [1] in mice to the effect that nociceptive sensitivity varies during the day, peaking in the morning and afternoon and falling later on. A difference between present and previous results involves the failure of the earlier report to find the effect in paw-lick latency (only jump latency varied diurnally) whereas all our measures (including paw lick) showed greater sensitivity in the daytime. This difference may be attributed to species differences. The increased sensitivity in the daytime is probably not due to arousal effects since rats are more active (aroused) at night; i.e., if greater arousal led to heightened nociceptive sensitivity, one would expect to see shorter latencies at night. The notion of diurnally varying endogenous opiate levels, as proposed by Frederickson et al. [1], is more consistent with the results.
TABLE 1
Measure
early mean
late mean
nociceptive 2.17 +_ 0.29 reaction latency(sec) n=20
2.40 _+ 0.52
paw lick latency (sec) n=20
4.05 -+ 1.36
4.92 +_ 2.92
tailflick latency
15.22 -+ 1.62
16.01 _+ 1.99
C o p y r i g h t © 1979 Brain Re s e a r c h Publications I n c . n 0 0 3 1 - 9 3 84/79/080419-02500.70/0
420
ROSENFELD AND RICE ACKNOWLEDGEMENTS This study was supported by NIH Grant GM-23696 to J. P. Rosenfeld.
REFERENCES Frederickson, R. C. A., V. Burgis and J. D. Edwards. Hyperalgesla induced by naloxone follows diurnal rhythm in responsitivity to painful stimuli. Science 198: 756, 1977.
Rosenfeld, J. P. and B. S. Holzman. Differential: effect of morphine on stimulation of primary versus higher order trigeminal terminals. Brain Res. 124: 367, 1977.
Diurnal Rhythms in Nociceptive Thresholds of Rats J. P E T E R R O S E N F E L D
A N D P E T E R E. R I C E
D e p a r t m e n t s o f Psychiatry and Psychology N o r t h w e s t e r n University Evanston-Chicago, IL R e c e i v e d 10 F e b r u a r y 1979 ROSENFELD, J. P. AND P. E. RICE. Diurnal rhythms in nociceptive thresholds of rats. PHYSIOL. BEHAV. 23: (2) 419-420, 1979.--Paw lick, tail flick, and other nociceptive reaction latencies were observed in rats to be longer in the evening than in the daytime, suggesting an endogenous opiate mediated decrease in pain sensitivity in the evening in comparison with the daytime. Naloxone
Endorphin
Enkephalin
Nociception
F R E D E R I C K S O N et al. [1] reviewed and helped resolve the controversy over the direct (hyperalgesic) action of naloxone by noting a diurnal rhythm in nociceptive sensiti~;ity of mice: If naloxone's opiate antagonism is mediated by opiate receptor blockage, the endogenous opiate action should also be subject to block, resulting in direct hyperalgesic effects of naloxone. If, however, endogenous opioid levels follow a diurnal rhythm such that during morning and afternoon hours (when most studies are done) the nociceptive thresholds are maximally depressed, a further depression by naloxone might go undetected. Frederickson et al. [1] noted a diurnal rhythm in hot-plate jump latency but not in pawlick latency in mice. The present study was undertaken to see if diurnal phenomena were observable in rats. Three nociceptive latencies were observed: (1) paw-lick latency (any paw) and (2) latency to nociceptive reaction [2] on a 49°C hotplate, and (3) tail flick latency. In the paw lick test, animals are placed on a 49°C hotplate and a stopwatch is started. It is stopped when any paw is licked in response to the nociceptive heat level being reached. The second latency involves an orientation response or a flinch/jump or a sudden scampering escape attempt, whichever comes first. In the tail flick test, a beam of intense light is focused on the tip of the rat's tail. A stopwatch is started when the light is turned on and stopped when the tail is flicked in response; this also turns off the light. Twenty male albino rats (400-450 g) were tested on the hot plate measures 4 times a day for 7 days each. A subsample of 9 of these was given tail-flick testing also. Testing times were 11 a.m., 4 p.m., 7 p.m. and 11 p.m.. The rats were housed on a lighting schedule which had lights on from 8 a.m. to 8 p.m. and off otherwise. Food and water were available ad lib. Means over the 7 days were determined for each of the 4 test times for each rat, and then the two earlier times and the two later times were separately averaged within rats to yield one early and one late test latency. The results are given in Table 1 in terms of
Diurnal
Pain
mean -4- standard deviation. Within-subject (correlated), two-tailed t-tests were done on each pair of means in the 3 rows above. The significant t-values for the 3 rows were 2.69 (p<0.02), 2.27 (p<0.05), and 2.74 (p<0.05), respectively. The results in rats agree with the earlier results of Frederickson et al. [1] in mice to the effect that nociceptive sensitivity varies during the day, peaking in the morning and afternoon and falling later on. A difference between present and previous results involves the failure of the earlier report to find the effect in paw-lick latency (only jump latency varied diurnally) whereas all our measures (including paw lick) showed greater sensitivity in the daytime. This difference may be attributed to species differences. The increased sensitivity in the daytime is probably not due to arousal effects since rats are more active (aroused) at night; i.e., if greater arousal led to heightened nociceptive sensitivity, one would expect to see shorter latencies at night. The notion of diurnally varying endogenous opiate levels, as proposed by Frederickson et al. [1], is more consistent with the results.
TABLE 1
Measure
early mean
late mean
nociceptive 2.17 +_ 0.29 reaction latency(sec) n=20
2.40 _+ 0.52
paw lick latency (sec) n=20
4.05 -+ 1.36
4.92 +_ 2.92
tailflick latency
15.22 -+ 1.62
16.01 _+ 1.99
C o p y r i g h t © 1979 Brain Re s e a r c h Publications I n c . n 0 0 3 1 - 9 3 84/79/080419-02500.70/0
420
ROSENFELD AND RICE ACKNOWLEDGEMENTS This study was supported by NIH Grant GM-23696 to J. P. Rosenfeld.
REFERENCES Frederickson, R. C. A., V. Burgis and J. D. Edwards. Hyperalgesla induced by naloxone follows diurnal rhythm in responsitivity to painful stimuli. Science 198: 756, 1977.
Rosenfeld, J. P. and B. S. Holzman. Differential: effect of morphine on stimulation of primary versus higher order trigeminal terminals. Brain Res. 124: 367, 1977.