Abstract ID: A5
Abstract Title: Gabapentin increases cerebrospinal fluid concentrations of norepinephrine in humans
Authors: De Goes S1, Eisenach J2, Curry R3
Wake Forest University Baptist Medical Center Winston Salem NC USA1, Wake Forest University Baptist Medical Center Winston Salem NC USA2, Wake Forest University Baptist Medical Center Winston Salem NC USA3
Poster Type: Poster
ABSTRACT BODY
Introduction: Gabapentin, originally developed to treat epilepsy and spasticity, has since received approval in the treatment of chronic pain. Despite intense research, gabapentin's mechanism for inducing analgesia remains unknown. Gabapentin does not interact with GABA receptors or alter GABA synthesis. It binds to the α2δ accessory protein of voltage-gated calcium channels; studies support its action on this target in the spinal cord and peripheral nerves. Recent evidence suggests a supraspinal mechanism of gabapentin in animals, by which it activates descending noradrenergic inhibition. The purpose of the current study was to determine whether this mechanism was present in humans, as evidenced by increases in cerebrospinal fluid (CSF) concentrations of norepinephrine after gabapentin administration.
Methods: Following human studies committee approval and written informed consent, 34 patients in this ongoing study scheduled for elective surgery under spinal anesthesia were recruited. Exclusion criteria included renal failure, leukopenia, and allergy to or current use of gabapentin. On the day of surgery, patients were randomized to receive either oral gabapentin, 1200 mg, or a placebo at least 90 min prior to spinal anesthesia. After insertion of the spinal needle, 3 ml CSF was withdrawn for norepinephrine analysis by HPLC. Pain scores using an 11 point Likert scale were obtained before surgery and on the first postoperative day, and opioid use in morphine equivalents for the first 24 hr measured. Groups were compared by Student’s t test or Mann Whitney U test as appropriate.
Results. Patients underwent abdominal, pelvic, or orthopedic surgery, with a similar proportion of procedures between groups. Preoperative pain was present in all but one patient, averaging 6.4 ± 0.5. CSF concentration of norepinephrine was 449 [348-528] (median [25th-75th percentiles]) in the gabapentin group compared to 361 [242-450] pg/ml in the placebo group (P=0.08). Of the 16 subjects receiving gabapentin and the 18 subjects receiving placebo, 4 in each group received Depodur for postoperative analgesia. Excluding these subjects, the 24 hr opioid consumption was 26 ± 6.7 (mean ± SEM) in the gabapentin group and 52 ± 13 mg in the placebo group (P=0.09). The groups did not differ in postoperative pain scores.
Discussion: The study will be completed in February, with a total enrollment of 50 subjects. Should current trends continue, we will observe statistically significant differences in CSF norepinephrine for the entire population (greater in gabapentin group) and postoperative opioid consumption in those not receiving Depodur/epidural postop (less in gabapentin group). These data are consistent with previous reports of opioid sparing from pre-operative gabapentin in surgical patients. In addition, the results indicate that gabapentin triggers descending noradrenergic inhibition in patients with preoperative pain and suggest that gabapentin’s effect may be enhanced by treatments which further augment this pathway.
Supported in part by NIH grant NS41386
ATTACHED FILES
Reg Anesth Pain Med 2005; 30(3):A5