Original Report| Volume 12, ISSUE 2, P222-227, February 2011

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The Influence of Non-Nociceptive Factors on Hot-Plate Latency in Rats

Published:August 27, 2010DOI:


      The hot plate is a widely used test to assess nociception. The effect of non-nociceptive factors (weight, sex, activity, habituation, and repeated testing) on hot-plate latency was examined. Comparison of body weight and hot-plate latency revealed a small but significant inverse correlation (light rats had longer latencies). Habituating rats to the test room for 1 hour prior to testing did not decrease hot-plate latency except for female rats tested on days 2 to 4. Hot-plate latency decreased with repeated daily testing, but this was not caused by a decrease in locomotor activity or learning to respond. Activity on the hot plate was consistent across all 4 trials, and prior exposure to a room-temperature plate caused a similar decrease in latency as rats tested repeatedly on the hot plate. Despite this decrease in baseline hot-plate latency, there was no difference in morphine antinociceptive potency. The present study shows that weight, habituation to the test room, and repeated testing can alter baseline hot-plate latency, but these effects are small and have relatively little impact on morphine antinociception.


      This manuscript shows that non-nociceptive factors such as body weight, habituation, and repeated testing can alter hot-plate latency, but these factors do not alter morphine potency. In sum, the hot-plate test is an easy to use and reliable method to assess supraspinally organized nociceptive responses.

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        • Ankier S.I.
        New hot plate tests to quantify antinociceptive and narcotic antagonist activities.
        Eur J Pharmacol. 1974; 27: 1-4
      1. Bannon AW, Malmberg AB: Models of nociception: Hot-plate, tail-flick, and formalin tests in rodents. Curr Protoc Neurosci:Chapter 8:Unit 8.9, 2007

        • Bardo M.T.
        • Hughes R.A.
        Exposure to a nonfunctional hot plate as a factor in the assessment of morphine-induced analgesia and analgesic tolerance in rats.
        Pharmacol Biochem Behav. 1979; 10: 481-485
        • Chesler E.J.
        • Wilson S.G.
        • Lariviere W.R.
        • Rodriguez-Zas S.L.
        • Mogil J.S.
        Identification and ranking of genetic and laboratory environment factors influencing a behavioral trait, thermal nociception, via computational analysis of a large data archive.
        Neurosci Biobehav Rev. 2002; 26: 907-923
        • Christina A.
        • Merlin N.
        • Vijaya C.
        Jayaprakash S Murugesh N: Daily rhythm of nociception in rats.
        J Circadian Rhythms. 2004; 2: 2
        • Eddy N.B.
        • Leimbach D.
        Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines.
        J Pharmacol Exp Ther. 1953; 107: 385-393
        • Gamble G.D.
        • Milne R.J.
        Repeated exposure to sham testing procedures reduces reflex withdrawal and hot-plate latencies: Attenuation of tonic descending inhibition?.
        Neurosci Lett. 1989; 96: 312-317
        • Gebhart G.F.
        • Mitchell C.L.
        Further studies on the development of tolerance to the analgesic effect of morphine: The role played by the cylinder in the hot plate testing procedure.
        Arch Int Pharmacodyn Ther. 1971; 191: 96-103
        • Gebhart G.F.
        • Mitchell C.L.
        The relative contributions of the testing cylinder and the heated plate in the hot plate procedure to the development of tolerance to morphine in rats.
        Eur J Pharmacol. 1972; 18: 56-62
        • Hunskaar S.
        • Berge O.G.
        • Hole K.
        A modified hot-plate test sensitive to mild analgesics.
        Behav Brain Res. 1986; 21: 101-108
        • Ingram S.L.
        • Fossum E.N.
        • Morgan M.M.
        Behavioral and electrophysiological evidence for opioid tolerance in adolescent rats.
        Neuropsychopharmacology. 2007; 32: 600-606
        • Jacob J.
        Some effects of morphine adaptive and learning behavior.
        in: Votava Z. Psychopharmacological Methods. Macmillan, New York, NY1963: 70-79
        • Knoll J.
        • Kelemen K.
        • Knoll B.
        Experimental studies on the higher nervous activity of animals: I. A method for the eleboration of a non-extinguishable conditioned reflex in the rat.
        Acta Physiol Hung. 1955; 8: 327-344
        • Lai Y.Y.
        • Chan S.H.
        Shortened pain response time following repeated algesiometric tests in rats.
        Physiol Behav. 1982; 28: 1111-1113
        • Lane D.A.
        • Morgan M.M.
        Antinociceptive tolerance to morphine from repeated nociceptive testing in the rat.
        Brain Res. 2005; 1047: 65-71
        • Le Bars D.
        • Gozariu M.
        • Cadden S.W.
        Animal models of nociception.
        Pharmacol Rev. 2001; 53: 597-652
        • Milne R.J.
        • Gamble G.D.
        • Holford N.H.
        Behavioural tolerance to morphine analgesia is supraspinally mediated: A quantitative analysis of dose-response relationships.
        Brain Res. 1989; 491: 316-327
        • Morgan M.M.
        • Fossum E.N.
        • Levine C.S.
        • Ingram S.L.
        Antinociceptive tolerance revealed by cumulative intracranial microinjections of morphine into the periaqueductal gray in the rat.
        Pharmacol Biochem Behav. 2006; 85: 214-219
        • Morgan M.M.
        • Fossum E.N.
        • Stalding B.M.
        • King M.M.
        Morphine antinociceptive potency on chemical, mechanical, and thermal nociceptive tests in the rat.
        J Pain. 2006; 7: 358-366
        • Morgan M.M.
        • Sohn J.H.
        • Liebeskind J.C.
        Stimulation of the periaqueductal gray matter inhibits nociception at the supraspinal as well as spinal level.
        Brain Res. 1989; 502: 61-66
        • O'Callaghan J.P.
        • Holtzman S.G.
        Quantification of the analgesic activity of narcotic antagonists by a modified hot-plate procedure.
        J Pharmacol Exp Ther. 1975; 192: 497-505
        • Plone M.A.
        • Emerich D.F.
        • Lindner M.D.
        Individual differences in the hotplate test and effects of habituation on sensitivity to morphine.
        Pain. 1996; 66: 265-270
        • Romero A.
        • Miranda H.F.
        • Puig M.M.
        Analysis of the Opioid-Opioid Combinations According to the Nociceptive Stimulus in Mice.
        Pharmacol Res. 2010; 61: 511-518
        • Stoffel E.C.
        • Ulibarri C.M.
        • Craft R.M.
        Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats.
        Pain. 2003; 103: 285-302
        • Suh H.H.
        • Fujimoto J.M.
        • Tseng L.F.
        Different radiant heat intensities differentiate intracerebroventricular morphine- from beta-endorphin-induced inhibition of the tail-flick response in the mouse.
        Eur J Pharmacol. 1992; 213: 337-341
      2. Taber RI: Predictive value of analgesic assays in mice and rats. Adv Biochem Psychopharmacol 8:191-211, 1973

        • Van Ree J.M.
        • Leys A.
        Behavioral effects of morphine and phencyclidine in rats: The influence of repeated testing before and after single treatment.
        Eur J Pharmacol. 1985; 113: 353-362
        • Van Waas M.
        • Soffie M.
        Differential environmental modulations on locomotor activity, exploration and spatial behaviour in young and old rats.
        Physiol Behav. 1996; 59: 265-271
        • Woolf G.
        • MacDonald A.L.
        The evaluation of the analgesic action of pethidine hydrochloride (Demerol).
        J Pharmacol Exp Ther. 1944; 80: 300-307