Abstract
Purpose: To seek behavioural, reflexive and histochemical evidence of long-lasting changes in nociceptive stimulus transmission induced by exposure to doses of pentobarbital that induce nocifensive hyperreflexia.
Methods: Nocifensive hyperreflexia was induced in 12 rats with 30 mg·kg−1 pentobarbitalip. Reflex latency times for withdrawal of the hind paw from noxious radiant heat were measured with an automated electronic timer. Subjective responses to noxious stimulation (licking or biting of the stimulated hindpaw) and the level of sedation were recorded. Histological sections of lumbar spinal cord were stained for immunoreactivity of the immediate-early-gene (IEG0, c-fos, in three rats that repeated threshold noxious radiant heat stimulation during the period of nocifensive hyperreflexia induced by 30 mg·kg−1 pentobarbitalip.
Results: Reflex withdrawal latency decreased by 32±8% of control values (P<0.001) following pentobarbital injection and returned to control values 120 min after drug injection. Once fully alert, pentobarbital-treated animals did not show any increase in nociceptive behaviour relative to saline-injected controls (P=0.41). Sustained noxious stimulation to the hindpaw in halothane-anesthetized animals was associated with an increase inc-fos immunoreactivity in the dorsal horn of the lumbar spinal cord ipsilateral to the stimulation (P<0.001). Threshold stimulation in the pentobarbital-treated animals was not associated with any increase inc-fos expression.
Conclusions: During pentobarbital-induced hyperreflexia, rats did not show any reflexive, behavioural, or histochemical evidence of long-lasting enhancement of nocifensive signal transmission. The results are consistent with previous observations that, in the absence of tissue injury, nocifensive hyperreflexia induced by barbiturates is a short-lived pharmacological effect.
Résumé
Ojectif: Découvrir les manifestations comportementales, réflexes et histochimiques de modifications persistantes de la transmission d’un stimulus nociceptif induit par l’exposition à des doses de pentobarbital qui provoquent une surréflectivité défensive.
Méthode: La surréflectivité défensive a été induite chez 12 rats avec 30 mg·kg−1 de pentobarbitalip. Les temps de latence réflexe nécessaire au retrait de la patte arrière d’une source de chaleur radiante ont été mesurés avec un chronomètre électronique automatisé. Les réponses subjectives à la stimulation désagréable (lécher ou mordre la patte stimulée) et le niveau de sédation ont été enregistrés. Des sections histologiques de la moelle épinière lombaire ont été colorées pour vérifier l’immunoréactivité du gène précoce une stimulation liminale novice répétée de chaleur radiante pendant la période de surréflectivité défensive induite par les 30 mg·kg−1 de pentobarbitalip.
Résultats: Le temps de latence réflexe a baissé de 32±8 % par rapport aux valeurs témoins (P<0,001) après l’injection de pentobarbital et est revenu aux valeurs témoins 120 min après l’injection du médicament. Une fois complètement réveillés, les animaux traités au pentobarbital n’ont pas affiché de comportement nociceptif accru comparés aux animaux témonis à qui on a injecté une solution salée (P=0,41). La stimulation nocive à la patte arrière, subie par les animaux anesthésiés à l’halothane, a été associée avec un accroissement de l’immunoréactivité au gènec-fos dans la corne supérieure de la moelle épinière lombaire homolatérale à la stimulation (P<0,001). La stimulation liminale chez les animaux traités au pentobarbital n’était pas accompagnée d’une augmentation de l7rsexpression dec-fos.
Conclusion: Pendant la surréflectivité liée au pentobarbital, les rats n’ont pas donné de signe réflexe, comportemental ou histochimique d’une augmentation persistante de la transmission du signal défensif. Ces résultats confirment des observations antérieures qui montraient qu’en l’absence de l’sion aux tissus la surréflectivité défensive induite par les barbituriques présente un effet pharmacologique de courte durée.
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This study was supported by the Medical Research Council of Canada (S.H.R.) and by the Canadian Anaesthetists’ Society — Burroughs-Wellcome Research Award (D.P.A.).
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Archer, D.P., Samanani, N. & Roth, S.H. Pentobarbital induces nocifensive hyperrflexia, not hyperalgesia in rats. Can J Anaesth 47, 687–692 (2000). https://doi.org/10.1007/BF03019003
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DOI: https://doi.org/10.1007/BF03019003