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

[La pré-administration intrathécale de fentanyl supprime efficacement l'expression de c-Fos provoquée par le formol dans la moelle épinière du rat]

From the Department of Anesthesiology, Miyazaki Medical College, Miyazaki, Japan.

Dr. Tadashi Nakamura, Department of Anesthesiology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. Phone: 81-985-85-2970; Fax: 81-985-85-7179; E-mail: zenigata{at}post1.miyazaki-med.ac.jp

Purpose: To investigate whether the timing of intrathecal administration of the opioid analgesic fentanyl, alters noxious stimulus-evoked neuronal activity in the rat spinal cord.

Methods: A 5% formalin solution was used as the noxious stimulant. For the pretreatment group, a dose of 0.001 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.

Results: Pretreatment and early post-treatment groups showed suppression of c-Fos activity compared to the vehicle (P <0.01). 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 <0.01). 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.

Conclusion: 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.

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