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Perioperative Pregabalin Reduces Neuropathic Pain at 6 Months after Total
Knee Arthroplasty (TKA)
Asokumar Buvanendran, MD, Scott S. Reuben, MD, Jeffrey S. Kroin, PhD., Mario Moric, PhD,
Kenneth J. Tuman, MD
Anesthesiology, Rush Medical College, Chicago, Illinois
Introduction: Pregabalin has been shown to be effective for the treatment of chronic neuropathic
pain (Pain Res Manag 2006; 11:16A; Curr Opin Anaesthesiol 2007; 20:456). This study was
designed to evaluate if pregabalin given prior to and for 14 days after total knee arthroplasty
(TKA) will reduce the prevalence of neuropathic pain at 3 and 6 months after surgery.
Methods: Following IRB approval, a total of 300 patients having primary TKA were enrolled in
this randomized, placebo-controlled, double-blind study. Patients were randomly assigned to 2
drug groups. Two hours prior to surgery, half of the patients received pregabalin 300 mg orally,
and the other half received matching placebo. In the operating room, patients were sedated with
midazolam and a combined spinal-epidural procedure performed. At completion of surgery,
epidural infusion of fentanyl/bupivacaine was initiated using continuous basal infusion with
superimposed patient-controlled bolus. Patients subsequently received repeated doses of
pregabalin 150 mg b.i.d. or placebo starting the day after surgery, with drug dosing continued
until day 14 post-surgery. The incidence of neuropathic pain was assessed by a blinded
investigator at 3 and 6 months post-surgery using the S-LANSS score, a valid diagnostic tool to
assess neuropathic pain, with patients scoring ≥12 considered to have neuropathic pain
(J Pain 2005; 6:149). The incidence of mechanical allodynia (stroking) or hyperalgesia (pressure)
was also recorded. Comparison between the 2 groups was by chi-squared test.
Results: There was no difference in demographics (age, weight, etc.) between the 2 groups. At 3
months post-TKA, the incidence of patients with neuropathic pain post-TKA was lower in the
pregabalin (1.8%) group compared to the placebo (14.2%) (P=0.0006) (fig). The incidence of
allodynia in the operated leg was also lower (P=0.020) at 3 months for the pregabalin group
(16.4%) than the placebo group (29.1%); the incidence of hyperalgesia in the operated leg was
lower (P=0.005) at 3 months for the pregabalin group (16.4%) than the placebo group (32.3%). At
6 months post-TKA, the incidence of patients with neuropathic pain post-TKA was lower in the
pregabalin (0.9%) group compared to the placebo (9.4%) (P=0.004) (fig). The incidence of
allodynia in the operated leg was also lower (P=0.004) at 6 months for the pregabalin group
(6.4%) than the placebo group (19.5%); the incidence of hyperalgesia in the operated leg was
lower (P=0.001) at 6 months for the pregabalin group (6.4%) than the placebo group (21.1%).

Discussion: Perioperative administration of pregabalin decreased the incidence of neuropathic
pain at 3 and 6 months after TKA. This suggests that pregabalin may be a useful perioperative
medication for decreasing the incidence of chronic pain for patients undergoing this surgical
procedure. [figure1]

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