BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Sufficient central nervous system drug concentrations are reached after oral administration of pregabalin, suggesting that postoperative painhypersensitivity can be reduced. Decreasing this acute brain or spinal cord excitability may prevent chronic pain from developing after surgery.
Authors: Ian Carroll; Jennifer Hah; Sean Mackey; Einar Ottestad; Jiang Ti Kong; Sam Lahidji; Vivianne Tawfik; Jarred Younger; Catherine Curtin Journal: J Reconstr Microsurg Date: 2013-03-05 Impact factor: 2.873