Canadian Journal of Anaesthesia

, Volume 48, Issue 10, pp 993–999 | Cite as

Intrathecal pre-administration of fentanyl effectively suppresses formalin evoked c-Fos expression in spinal cord of rat

  • Tadashi NakamuraEmail author
  • Mayumi Takasaki
Regional Anesthesia and Pain



To investigate whether the timing of intrathecal administration of the opioid analgesic fentanyl, alters noxious stimulusevoked neuronal activity in the rat spinal cord.


A 5% formalin solution was used as the noxious stimulant. For the pretreatment group, adose of 0.00l to 0.5 μg of fentanyl was injected intrathecally ten minutes prior to formalin injection. Early and late post-treatment groups received 0.01 to 0.5 μg fentanyl, five and 60 min after formalin injection respectively. The effect of fentanyl was confirmed with naloxone. The level of c-Fos expression was determined in each treatment group to indicate neuronal activity.


Pretreatment and early post-treatment groups showed suppression of c-Fos activity compared to the vehicle (P < 0.0l). The late post-treatment group showed no difference in c-Fos activity compared to the vehicle (P = NS). Pretreatment with fentanyl showed the most profound suppression of c-Fos expression (P < 0.0l). In addition, pretreatment injection showed a greater suppression of c-Fos activity in the deep (14.6% of control) compared to the superficial laminae (32.7% of control;P < 0.01), whereas the early post-treatment group showed a universal decrease in c-Fos activity (49.2% of control in laminae I and II, 50.4% of control in laminae III and IV and 51.8% of control in laminae V and VI). Naloxone reversed the action of fentanyl on c-Fos activity.


Inasmuch as: 1) c-Fos expression can be equated with behavioural changes; 2) injection of formalin is an appropriate model of surgical trauma; and 3) animal data can be transports to humans, these results suggest that fentanyl would be an effective pre-emptive analgesic.


Fentanyl Naloxone Dorsal Horn Spinal Dorsal Horn Formalin Injection 
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La pré-administration intrathêcale de fentanyl supprime efficacement l’expression de c-Fos provoquée par le formol dans la moelle épinière du rat



Vérifier si le moment choisi pour l’administration intrathécale de l’analgésique opioïde fentanyl agit sur l’activité nerveuse induite par un stimulus nocif dans la moelle épinière du rat.


Une solution de formol à 5 % a servi de stimulus nocif Dans le groupe de prétraitement, une dose de 0,001 à 0,5 μg de fentanyl a été administrée en injection intrathécale dix minutes avant l’injection de formol. Dans les groupes de post-traitement hâtif et tardif, on a donné de 0,01 à 0,5 μg de fentanyl, cinq et 60 min après le formol, respectivement, Leffet du fentanyl a été confirmé par la naloxone. Le niveau déxpression de c-Fos a été déterminé dans chaque groupe pour indiquer l’activité neuronale.


Léxamen des rats des groupes de prétraitement et de post-traitement hâtif comparés au groupe ayant reçu l’excipient, a montré une suppression de l’activité de c-Fos (P < 0,01). Le groupe de post-traitement tardif, comparé à l’excipient, ne présentait aucune différence d’activité de c-Fos (P = NS). Le prétraitement au fentanyl a permis la suppression la plus profonde de l’expression de c-Fos (P < 0,01). De plus, l’injection de prétraitement a entraîné une suppression plus importante dans les lames profondes (14,6 % des témoins) comparées aux lames superficielles (32,7 % des témoins; P < 0,01), tandis que le post-traitement hâtif a provoqué une baisse générale de l’activité de c-Fos (49,2 % des témoins dans les lames I et II, 50,4 % des témoins dans les lames III et IV et 51,8 % des témoins dans les lames V et VI). La naloxone a renversé l’action du fentanyl sur l’activité de c-Fos.


Étant donné: 1) que l’expression de c-Fos peut être mise en équation avec les changements comportementaux; 2) que l’injection de formol constitue un modèle approprié de traumatisme chirurgical et 3) que les données animales peuvent être extrapolées à l’humain, ces résultats suggèrent que le fentanyl serait un analgésique préventif efficace.


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Copyright information

© Canadian Anesthesiologists 2001

Authors and Affiliations

  1. 1.Department of AnesthesiologyMiyazaki Medical CollegeKiyotake, MiyazakiJapan

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