Canadian Journal of Anaesthesia

, Volume 47, Issue 3, pp 273–279 | Cite as

Propofol directly depresses lumbar dorsal horn neuronal responses to noxious stimulation in goats

  • Joseph F. Antognini
  • Xiao Wei Wang
  • Marla Piercy
  • Earl Carstens
Laboratory Investigations


Purpose: We tested the hypothesis that propofol, acting in the brain, would either enhance, or have no effect, on lumbar dorsal horn neuronal responses to a noxious mechanical stimulus applied to the hindlimb. We recorded the response of lumbar dorsal horn neurons during differential delivery of propofol to the brain and torso of goats.

Methods: Goats were anesthetized with isoflurane and neck dissections performed which permitted cranial bypass. A laminectomy was made to allow microelectrode recording of lumbar dorsal horn neuronal activity. Isoflurane was maintained at 0.8±0.1 % to both head and torso throughout the study. During cranial bypass propofol was separately administered to the torso (1 mg·kg−1, n=7; 3.75 mg·kg−1, n=8) or cranial (0.04 mg·kg−1, n=7; 0.14 mg·kg−1, n=8) circulations.

Results: Propofol administered to the torso depressed dorsal horn neuronal responses to noxious stimulation: low dose: 500±243 to 174±240 impulses·min−1 at one minute post-injection,P<0.001; high dose: 478 ± 204 to 91±138 impulses·min−1 at one minute post-injection,P<0.05). Propofol administered to the cranial circulation had no effect: low dose: 315±150 to 410±272 impulses·min−1,P>0.05; high dose: 462±261 to 371±196 impulses·min−1,P>0.05.

Conclusions: These data indicate that propofol has a direct depressant effect on dorsal horn neuronal responses to noxious stimulation, with little or no indirect supraspinal effect.


Dorsal Horn Noxious Stimulation Spinal Dorsal Horn Neuron Minute Postinjection Lumbar Dorsal Horn 


Objectif: Vérifier si le propofol, qui agit sur le cerveau, stimulera les réponses neuronales de la corne supérieure lombaire, ou n’aura aucun effet, après l’application d’un stimulus mécanique nocif aux pattes arrières des chèvres. Les réponses ont été enregistrées pendant l’administration différentielle de propofol au cerveau et à la région thoracique.

Méthode: Les chèvres ont été anesthésiées avec de l’isoflurane et la dissection du cou a été réalisée pour permettre une dérivation crânienne. Une laminectomie a été faite pour faciliter l’enregistrement de l’activité neuronale de la corne supérieure lombaire par microélectrode. L’isoflurane a été maintenu à 0,8±0,1 % à la tête et au tronc tout au long de l’étude. Pendant la dérivation crânienne, le propofol a été administré séparément dans la circulation thoracique (l mg·kg−1, n=7; 3,75 mg·kg−1, n=8) ou à la tête (0,04 mg·kg−1, n=7; 0,14 mg·kg−1, n=8).

Résultats: Le propofol administré au niveau thoracique a réduit les réponses neuronales à un stimulus nocif: faible dose: 500±243 à 174±240 impulsions·min−1 à une minute postinjection,P<0.001; forte dose: 478±204 à 91±138 impulsions·min−1 à une minute postinjection,P<0,05). Le propofol dans la circulation crânienne n’a pas eu d’effet: faible dose: 315±150 à 410±272 impulsions·min−1,P>0.05; forte dose: 462±261 à 371±196 impulsions·min−1,P>0,05.

Conclusion: Ces données indiquent que le propofol a un effet dépresseur direct sur les réponses neuronales de la corne supérieure à une stimulation nocive, avec un léger effet supraspinal indirect ou sans effet supraspinal.


  1. 1.
    Antognini JF, Schwartz K Exaggerated anesthetic requirements in the preferentially anesthetized brain. Anesthesiology 1993; 79: 1244–9.PubMedGoogle Scholar
  2. 2.
    Rampil IJ. Anesthetic potency is not altered after hypothermic spinal cord transection in rats. Anesthesiology 1994; 80: 606–10.PubMedCrossRefGoogle Scholar
  3. 3.
    Willis WD, Westlund KN. Neuroanatomy of the pain system and of the pathways that modulate pain. J Clin Neurophysiol 1997; 14: 2–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Namiki A, Collins JG, Kitahata LM, Kikuchi H, Homma E, Thalhammer JG. Effects of halothane on spinal neuronal responses to graded noxious heat stimulation in the cat. Anesthesiology 1980; 53: 475–80.PubMedCrossRefGoogle Scholar
  5. 5.
    de Jong RH, Robles R, Heavner JE. Suppression of impulse transmission in the cat’s dorsal horn by inhalation anesthetics. Anesthesiology 1970; 32: 440–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Kishikawa K, Uchida H, Yamamori Y, Collins JG. Low-threshold neuronal activity of spinal dorsal horn neurons increases during REM sleep in cats: comparison with effects of anesthesia. J Neurophysiol 1995; 74: 763–9.PubMedGoogle Scholar
  7. 7.
    Grounds RM, Lalor JM, Lumley J, Royston D, Morgan M. Propofol infusion for sedation in the intensive care unit: preliminary report. BMJ 1987; 294: 397–400.PubMedGoogle Scholar
  8. 8.
    Ewen A, Archer DP, Samanani N, Roth SH. Hyperalgesia during sedation: effects of barbiturates and propofol in the rat. Can J Anaesth 1995; 42: 532–40.PubMedCrossRefGoogle Scholar
  9. 9.
    Uchida H, Kishikawa K, Collins JG. Effect of propofol on spinal dorsal horn neurons. Comparison with lack of ketamine effects. Anesthesiology 1995; 83: 1312–22.PubMedCrossRefGoogle Scholar
  10. 10.
    Antognini JF, Kien ND. A method for preferential delivery of volatile anesthetics to thein situ goat brain. Anesthesiology 1994; 80: 1148–54.PubMedCrossRefGoogle Scholar
  11. 11.
    Antognini JF, Jinks S, Buzin V, Carstens E. A method for differential delivery of intravenous drugs to the head and torso of the goat. Anesth Analg 1998; 87: 1450–2.PubMedCrossRefGoogle Scholar
  12. 12.
    Forster C, Handwerker HO. Automatic classification and analysis of microneurographic spike data using a PC/AT. J Neurosci Methods 1990; 31: 109–18.PubMedCrossRefGoogle Scholar
  13. 13.
    Reid J, Nolan AM, Welsh E. Propofol as an induction agent in the goat: a pharmacokinetic study. J Vet Pharmacol Ther 1993; 16: 488–93.PubMedCrossRefGoogle Scholar
  14. 14.
    Fleetwood-Walker SM, Mitchell R, Hope PJ, Molony V, Iggo A An2 receptor mediates the selective inhibition by noradrenaline of nociceptive responses of dientified dorsal horn neurones. Brain Res 1985; 334: 243–54.PubMedCrossRefGoogle Scholar
  15. 15.
    Davies J, Quinlan JE. Selective inhibition of responses of feline dorsal horn neurones to noxious cutaneous stimuli by tizanidine (DS103-282) and noradrenaline: involvement of2-adrenoceptors. Neuroscience 1985; 16: 673–82.PubMedCrossRefGoogle Scholar
  16. 16.
    Mazzi G, Schinella M. Simple and practical high-performance liquid chromatographic assay of propofol in human blood by phenyl column chromatography with electrochemical detection. J Chromatogr A 1990; 528: 537–41.Google Scholar
  17. 17.
    Chan K, So APC. The measurement of propofol in human blood samples by liquid chromatography. Meth Find Exp Clin Pharmacol 1990; 12: 135–9.Google Scholar
  18. 18.
    Zar JH. Biostatistical Analysis, 4th ed. Upper Saddle River, NJ: Prentice-Hall, 1999: 273–81.Google Scholar
  19. 19.
    Jewett BA, Gibbs LM, Tarasiuk A, Kendig JJ. Propofol and barbiturate depression of spinal nociceptive neurotransmission. Anesthesiology 1992; 77: 1148–54.PubMedCrossRefGoogle Scholar
  20. 20.
    Petersen-Felix S, Arendt-Nielsen L, Bak P, Fisher M, Zbinden AM. Psychophysical and electrophysiological responses to experimental pain may be influenced by sedation: comparison of the effects of a hypnotic (propofol) and an analgesic (alfentanil). Br J Anaesth 1996; 77: 165–71.PubMedGoogle Scholar
  21. 21.
    Anker-Møller E, Spangsberg N, Arendt-Nielsen L, Schultz P, Kristensen MS, Bjerring P. Subhypnotic doses of thiopentone and propofol cause analgesia to experimentally induced acute pain. Br J Anaesth 1991; 66: 185–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Wilder-Smith OHG, Kolletzki M, Wilder-Smith CH. Sedation with intravenous infusions of propofol or thiopentone. Effects on pain perception. Anaesthesia 1995; 50: 218–22.PubMedCrossRefGoogle Scholar
  23. 23.
    Sanna E, Mascia MP, Klein RL, Whiting PJ, Biggio G, Harris RA. Actions of the general anesthetic propofol on recombinant human GABAA receptors: influence of receptor subunits. J Pharmacol Exp Ther 1995; 274: 353–60.PubMedGoogle Scholar
  24. 24.
    Nadeson R, Goodchild CS. Antinociceptive properties of propofol: involvement of spinal cord —aminobutyric acidA receptors. J Pharmacol Exp Ther 1997; 283: 1181–6.Google Scholar
  25. 25.
    Rebberg B, Duch DS. Suppression of central nervous system sodium channels by propofol. Anesthesiology 1999; 91: 512–20.CrossRefGoogle Scholar
  26. 26.
    Jinks S, Antognini JF, Carstens E, Buzin V, Simons C. Isoflurane can indirectly depress lumbar dorsal horn activity in the goat via action within the brain. Br J Anaesth 1999; 82: 244–9.PubMedGoogle Scholar
  27. 27.
    Carstens E, Gilly H, Schreiber H, Zimmermann M. Effects of midbrain stimulation and iontophoretic application of serotonin, noradrenaline, morphine and GABA on electrical thresholds of afferent C- and A- fibre terminals in cat spinal cord. Neuroscience 1987; 21: 395–406.PubMedCrossRefGoogle Scholar
  28. 28.
    Carstens E. Inhibition of rat spinothalamic tract neuronal responses to noxious skin heating by stimulation in midbrain periaqueductal gray or lateral reticular formation. Pain 1988; 33: 215–24.PubMedCrossRefGoogle Scholar
  29. 29.
    Hori Y, Lee KH, Chung JM, Endo K, Willis WD. The effects of small doses of barbiturate on the activity of primate nociceptive tract cells. Brain Res 1984; 307: 9–15.PubMedCrossRefGoogle Scholar

Copyright information

© Canadian Anesthesiologists 2000

Authors and Affiliations

  • Joseph F. Antognini
    • 1
  • Xiao Wei Wang
    • 1
  • Marla Piercy
    • 1
  • Earl Carstens
    • 2
  1. 1.From the Department of Anesthesiology and Pain ManagementUniversity of California, DavisDavisUSA
  2. 2.Section of Neurobiology, Physiology and, and BehaviorUniversity of California, DavisDavisUSA

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