Otto K, Adams H A
Zentrales Tierlaboratorium der Medizinischen Hochschule Hannover.
Anasthesiol Intensivmed Notfallmed Schmerzther. 2005 Jan;40(1):25-31. doi: 10.1055/s-2004-826201.
To evaluate the effect of the non-steroidal anti-inflammtory drug carprofen on the lumbar cerebrospinal fluid (CSF) concentration of noradrenaline (NA) and serotonin (5-HT) in non-stimulated (Part I) and surgically stimulated (Part II) sheep.
In a prospective controlled study the effects of a single intravenous (i. v.) bolus injection of 4 mg/kg carprofen (CARP; n = 14), 0.01 mg/kg fentanyl (FENT; n = 12) or 0.9 % saline solution (NaCl; n = 13) on lumbar CSF concentrations of NA and 5-HT were evaluated in non-stimulated sheep. In addition, CSF concentrations were evaluated in isoflurane-anaesthetised sheep at different time points T1 (30 min after i. v. treatment with 4 mg/kg carprofen [n = 8] or saline [n = 7], T2 (20 min of constant end-tidal isoflurane concentration of 2.4 %) and T3 (during stifle arthroscopy at 2.4 % end-tidal isoflurane).
CSF concentrations of NA (NaCl: 170.23 +/- 16.86 pg/ml [x +/- SEM], CARP: 200.79 +/- 28.94 pg/ml, FENT: 209.58 +/- 27.67 pg/ml; p = 0.524) and 5-HT (NaCl: 2752.46 +/- 413.87 pg/ml, FENT: 2969.08 +/- 684.05 pg/ml, CARP: 3232.93 +/- 713.93 pg/ml; p = 0.978) were not significantly different between the three treatment groups of non-stimulated sheep. In the anaesthetised sheep, mean CSF-5-HT at T3 (NaCl: 6670.25 +/- 313.63 pg/ml; CARP: 4080.80 +/- 539.59 pg/ml) was significantly increased compared to T1 (NaCl: 2818.4 +/- 1104.54 pg/ml, p < 0.001; CARP: 2926.13 +/- 818.66 pg/ml, p = 0.022) and T2 (NaCl: 2593.67 +/- 618.89 pg/ml, p = 0.002; CARP: 2724.13 +/- 395.39 pg/ml, p = 0.012) in both treatment groups. Moreover, mean CSF-5-HT at T3 in the saline group was significantly higher (p = 0.006) compared to the CARP-group. Unlike changes in CSF-5-HT, no significant changes in mean CSF-NA were recorded neither within nor between the two treatment groups.
During arthroscopy in isoflurane-anaesthetised sheep, surgical stimuli may significantly increase mean CSF-5-HT concentration. This effect can be attenuated by pre-treatment with 4 mg/kg carprofen intravenously. Therefore, the analgesic effects of carprofen may be at least in part mediated by central serotonergic mechanisms.
评估非甾体抗炎药卡洛芬对未受刺激（第一部分）和手术刺激（第二部分）绵羊腰椎脑脊液（CSF）中去甲肾上腺素（NA）和5-羟色胺（5-HT）浓度的影响。
在一项前瞻性对照研究中，评估单次静脉推注4mg/kg卡洛芬（CARP；n = 14）、0.01mg/kg芬太尼（FENT；n = 12）或0.9%盐溶液（NaCl；n = 13）对未受刺激绵羊腰椎CSF中NA和5-HT浓度的影响。此外，在异氟烷麻醉的绵羊中，于不同时间点T1（静脉注射4mg/kg卡洛芬[n = 8]或生理盐水[n = 7]后30分钟）、T2（呼气末异氟烷浓度恒定为2.4%持续20分钟）和T3（膝关节镜检查时呼气末异氟烷浓度为2.4%）评估CSF浓度。
未受刺激绵羊的三个治疗组之间，CSF中NA（NaCl：170.23±16.86pg/ml[x±SEM]，CARP：200.79±28.94pg/ml，FENT：209.58±27.67pg/ml；p = 0.524）和5-HT（NaCl：2752.46±413.87pg/ml，FENT：2969.08±684.05pg/ml，CARP：3232.93±713.93pg/ml；p = 0.978）浓度无显著差异。在麻醉绵羊中，与T1（NaCl：2818.4±1104.54pg/ml，p < 0.001；CARP：2926.13±818.66pg/ml，p = 0.022）和T2（NaCl：2593.67±618.89pg/ml，p = 0.002；CARP：2724.13±395.39pg/ml，p = 0.012）相比，两个治疗组在T3时的平均CSF - 5-HT均显著升高。此外，生理盐水组T3时的平均CSF - 5-HT显著高于CARP组（p = 0.006）。与CSF - 5-HT的变化不同，两个治疗组内及组间的平均CSF - NA均未记录到显著变化。
在异氟烷麻醉的绵羊进行关节镜检查期间，手术刺激可显著提高平均CSF - 5-HT浓度。静脉注射4mg/kg卡洛芬预处理可减弱这种效应。因此，卡洛芬的镇痛作用可能至少部分由中枢5-羟色胺能机制介导。
