Experimental studies on the central analgesic effect of the non-steroidal anti-inflammatory drug carprofen in a sheep model - Preliminary results

Objective: 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 1) and surgically stimulated (Part 11) sheep. Methods: 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/kufentanyl (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). Results: CSF concentrations of NA (NaCl: 170.23+/-16.86 pg/ml [x+/-SEM], CARP: 200.79+/-28.94 palmi, 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 (mNaCl: 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 5-HT, no significant changes in mean CSF-NA were recorded neither within nor between the two treatment groups. Conclusion: 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.