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Hot plate test

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Thehot plate testis atest of the pain responsein animals, similar to thetail flick test.Both hot plate and tail-flick methods are used generally for centrally acting analgesic,[1]while peripherally acting drugs are ineffective in these tests but sensitive to acetic acid-inducedwrithingtest.[2]

The hot plate test is used in basicpainresearch and intestingthe effectiveness ofanalgesicsby observing the reaction to pain caused by heat. It was proposed by Eddy and Leimbach in 1953.[3]They used a behavioral model ofnociceptionwhere behaviors such as jumping and hind paw-licking are elicited following a noxious thermal stimulus. Licking is a rapid response to painful thermal stimuli that is a direct indicator ofnociceptive threshold.Jumping represents a more elaborated response, with a latency, and encompasses an emotional component of escaping.[4]

Procedure

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  • A transparent glass cylinder is used to keep the animal on the heated surface of the plate.[5]
  • The temperature of the hot plate is set using a thermoregulated water-circulated pump.
  • The time of latency is defined as the time period between the zero point, when the animal is placed on the hot plate surface, and the time when the animal licks its paw or jumps off to avoid thermal pain.[6][7]

Research findings

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Sex studies using antidepressants

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Significant differences in pain sensitivity in male and female mice have been observed in laboratory studies.[citation needed]TheSSRIantidepressantparoxetinedid not display a gender difference in antinociceptive effects in mice.[8]

Ion channels

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Voltage-gated ion channelsare implicated in pain sensation and transmission signaling mechanisms within bothperipheralnociceptors and thespinal cord.Specific ion channel isoforms such as Nav1.7 and Nav1.8sodium channelsand Cav3.2 T-typecalcium channelshave distinct pro-nociceptive roles.[9]

Opioid receptors

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Activation of theμ-opioid receptor(MOR) andnorepinephrine reuptake inhibition(NRI) are mechanisms of acute and chronic pain. OPRM1 knockout mice were used to determine the relative contribution of MOR activation totapentadolandmorphineinduced analgesia. Wild-type mice exhibited an antinociceptive effect ten times that of OPM1 knockouts. However, the OPRM1 knockouts still exhibited a slight analgesic effect to tapentadol but not to morphine. This indicated that the antinociceptive effect of tapentadol is based on a combined mechanism of action involving both MOR and NRI.[10]

Benzodiazepines and GABA receptors

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Diazepamis aGABAA receptorbenzodiazepineligandthat is ananxiety modulator.Studies using diazepam with the hot plate test showed that diazepam modified the behavioral structure of the pain response not from pain modulation but rather by reducing anxiety levels.[11]

Ethics

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Further information:Animal testing

The Ethical Committee of the International Association for the Study of Pain has developed guidelines for the ethical use of this procedure.[12]In the United States, such experiments must be approved by anInstitutional Animal Care and Use Committee.[13]

References

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  1. ^Carlsson, Karl-Heinz; Jurna, Ilmar (1987). "Depression by flupirtine, a novel analgesic agent, of motor and sensory responses of the nociceptive system in the rat spinal cord".European Journal of Pharmacology.143(1): 89–99.doi:10.1016/0014-2999(87)90738-2.ISSN0014-2999.PMID3691652.
  2. ^Matera, Carlo; Flammini, Lisa; Quadri, Marta; Vivo, Valentina; Ballabeni, Vigilio; Holzgrabe, Ulrike; Mohr, Klaus; De Amici, Marco; Barocelli, Elisabetta; Bertoni, Simona; Dallanoce, Clelia (2014). "Bis(ammonio)alkane-type agonists of muscarinic acetylcholine receptors: Synthesis, in vitro functional characterization, and in vivo evaluation of their analgesic activity".European Journal of Medicinal Chemistry.75:222–232.doi:10.1016/j.ejmech.2014.01.032.ISSN0223-5234.PMID24534538.
  3. ^Eddy, NB; Leimbach, D (1953)."Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines".J Pharmacol Exp Ther.107(3): 385–393.PMID13035677.
  4. ^ESPEJO, E; Mir, D (30 September 1993). "Structure of the rat's behaviour in the hot plate test".Behavioural Brain Research.56(2): 171–176.doi:10.1016/0166-4328(93)90035-O.PMID8240711.S2CID4022669.
  5. ^Hunskaar, Steinar; Berge, Odd-Geir; Hole, Kjell (1 August 1986). "A modified hot-plate test sensitivie to mild analgesics".Behavioural Brain Research.21(2): 101–108.doi:10.1016/0166-4328(86)90088-4.PMID3755945.S2CID3992246.
  6. ^Ripoll N, Hascoet M, Bourin M. The four-plates test: Anxiolytic or analgesic paradigm? Progress in Neuro-Psychopharmacology and Biological Psychiatry, July 2006 vol. 30 issue 5, 873-880.
  7. ^Tzschentke, T. M.; Christoph, T.; Kogel, B.; Schiene, K.; Hennies, H.-H.; Englberger, W.; Haurand, M.; Jahnel, U.; Cremers, T. I. F. H.; Friderichs, E.; De Vry, J. (23 July 2007). "( )-(1R,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol Hydrochloride (Tapentadol HCl): a Novel -Opioid Receptor Agonist/Norepinephrine Reuptake Inhibitor with Broad-Spectrum Analgesic Properties".Journal of Pharmacology and Experimental Therapeutics.323(1): 265–276.doi:10.1124/jpet.107.126052.PMID17656655.S2CID942191.
  8. ^Duman, E., Kesim, M., Kadioglu, M., Ulku, C., Kalyoncu, N., Yaris, E. 2006. Effect of gender on antinociceptive effect of paroxetine in hot plate test in mice. Progress in Neuro-Pharmacology and Biological Psychiatry. 30. 292–296.
  9. ^Hildebrand, M.; Smith, P.; Bladen, C.; Eduljee, C.; Xie, J.; Chen, L.; Fee-Maki, M.; Doering, C.; Mezeyova, J.; et al. (2011). "A novel slow-inactivation-specific ion channel modulator attenuates neuropathic pain".Pain.152(4): 833–843.doi:10.1016/j.pain.2010.12.035.hdl:1880/106710.PMID21349638.S2CID29622197.
  10. ^Kögel, B.; De Vry, J.; Tzschentke, T.; Christoph, T. (2011). "The antinociceptive and antihyperalgesic effect of tapentadol is partially retained in OPRM1 (μ-opioid receptor) knockout mice".Neuroscience Letters.491(2): 104–107.doi:10.1016/j.neulet.2011.01.014.PMID21232580.S2CID21141629.
  11. ^Casarrubea, M.; Sorbera, F.; Santangelo, A.; Crescimanno, G. (2012). "The effects of diazepam on the behavioral structure of the rat's response to pain in the hot-plate test: Anxiolysis vs. Pain modulation".Neuropharmacology.63(2): 310–321.doi:10.1016/j.neuropharm.2012.03.026.PMID22521500.S2CID21342382.
  12. ^Zimmermann, M. (1983). "Ethical guidelines for investigations of experimental pain in conscious animals".Pain.16(2): 109–10.CiteSeerX10.1.1.651.9572.doi:10.1016/0304-3959(83)90201-4.PMID6877845.S2CID38778262.
  13. ^Institutional Animal Care and Use Committee
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