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Intrathecal neurokinin-1 receptor antagonist reduces isoflurane MAC in rats
K Ishizaki1, S Karasawa, K Takahashi
1Department of Anesthesiology and Reanimatology, Gunma University School of Medicine, Maebashi, Japan. ishizaki@news.sb.gunma-u.ac.jp
Purpose:
To study the effects of intrathecal administration of a neurokinin-I(NK-I) receptor antagonist (CP96,345) on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in anaesthetized rats, and on the locomotive activity of conscious rats.
Methods:
Wistar rats (n = 36) were fitted with indwelling intrathecal catheters, and the MAC of isoflurane was determined following the intrathecal administration of saline (control group) or the NK-I receptor antagonist CP96,345 (CP) at 1, 10 and 100 micrograms. Subsequently a reversal dose of intrathecal Substance P (SP) at 1, 10 and 100 micrograms was administered and MAC isoflurane was redetermined. Conscious rats (n = 35) were also examined for the presence of locomotor dysfunction following intrathecal administration of CP and SP. Animals were randomly assigned to each treatment group and the investigators were blinded.
Results:
CP at 10 and 100 micrograms reduced MAC isoflurane by 9.9% and 15.3%, respectively (P < 0.05). Intrathecal administration of SP reversed the decreases in MAC by CP; however, locomotive activity was not changed.
Conclusion:
These results suggest that the NK-1 receptor plays an important role in determining the MAC of isoflurane by inhibition of pain transmission in the spinal cord.