Department of Anesthesiology, Rush Medical College at Rush University Medical Center, Chicago, IL 60612, USA.
Reg Anesth Pain Med. 2010 Nov-Dec;35(6):535-8. doi: 10.1097/AAP.0b013e3181fa6b7a.
Central spinal cord sensitization can occur during surgery and may lead to persistent pain after surgery. Pregabalin has been shown to decrease central sensitization in experimental pain paradigms, and so the same antihyperalgesic effect of pregabalin may occur during and immediately after surgery. Our study investigated whether a single 300-mg dose of pregabalin in patients has sufficient central nervous system bioavailability to be useful under acute conditions where brain or spinal cord excitability may lead to long-term disease, such as chronic pain.
Nine patients undergoing primary total knee replacement received pregabalin 300 mg orally, 1 hr before surgery. An intrathecal catheter was inserted for anesthesia, postoperative analgesic drug administration, and cerebrospinal fluid (CSF) sampling. Blood and CSF were then simultaneously sampled at 2, 4, 6, 8, and 24 hrs after oral pregabalin administration. Pregabalin concentration in plasma and CSF was measured using a validated high-pressure liquid chromatography assay.
By 2 hrs after pregabalin administration, the CSF pregabalin concentration is high enough (0.115 μg/mL) to have anticonvulsant activity, and by 6 hrs after pregabalin administration, the CSF pregabalin level is high enough (0.359 μg/mL) to reduce central nervous system hypersensitivity. The median time to peak pregabalin concentration in CSF was at 8 hrs. The pregabalin CSF/plasma based on area under the curve (AUC[0-24 hrs]) was 0.098 ± 0.016, and for AUC[0-∞], the ratio was 0.176 ± 0.064.
Sufficient central nervous system drug concentrations are reached after oral administration of pregabalin, suggesting that postoperative pain hypersensitivity can be reduced. Decreasing this acute brain or spinal cord excitability may prevent chronic pain from developing after surgery.
脊髓中枢敏化可能发生在手术过程中，并可能导致手术后持续疼痛。普瑞巴林已被证明可减少实验性疼痛模型中的中枢敏化，因此普瑞巴林可能在手术中和手术后立即产生相同的抗痛觉过敏作用。我们的研究旨在探讨在可能导致长期疾病（如慢性疼痛）的急性情况下，即大脑或脊髓兴奋性可能导致长期疾病的情况下，单次口服 300 毫克普瑞巴林是否对患者的中枢神经系统具有足够的生物利用度。
9 例接受初次全膝关节置换术的患者在手术前 1 小时口服普瑞巴林 300mg。插入鞘内导管用于麻醉、术后镇痛药物给药和脑脊液（CSF）采样。然后在口服普瑞巴林后 2、4、6、8 和 24 小时同时采集血液和 CSF。采用经验证的高压液相色谱法测定血浆和 CSF 中普瑞巴林的浓度。
普瑞巴林给药后 2 小时，CSF 中普瑞巴林的浓度足以达到抗惊厥作用（0.115μg/ml），给药后 6 小时，CSF 中普瑞巴林的浓度足以降低中枢神经系统的敏感性（0.359μg/ml）。CSF 中普瑞巴林达峰时间的中位数为 8 小时。基于 CSF 中的 AUC（0-24 小时）的普瑞巴林 CSF/血浆比值为 0.098±0.016，AUC（0-∞）比值为 0.176±0.064。
口服普瑞巴林后可达到足够的中枢神经系统药物浓度，提示术后疼痛敏化可降低。降低这种急性脑或脊髓兴奋性可能防止术后慢性疼痛的发生。
