Effects of Oral Pregabalin on Spinal Neurotransmitters in Patients Undergoing Total Knee Replacement (TKA)

Gabapentin and the related more potent compound pregabalin have been shown to reduce postoperative pain in animal models (1). Pregabalin given before and after surgery reduced opioid use following spinal fusion surgery (2). Studies have identified the alpha 2 delta auxiliary subunit of voltage-gated calcium channels as the molecular target of pregabalin (and gabapentin), although the specific spinal site of action (presynaptic, postsynaptic) is not known.

Total knee arthroplasty (TKA) has proved to be a successful surgical treatment of knee joints affected by osteoarthritis. Currently in the United States, more than 400,000 TKAs are performed every year with reported success rates ranging from 85% to 90% (American Academy). In an aging population, the number of annual TKA procedures is expected to reach 3.48 million by the year 2030 (3).

TKA is associated with considerable postoperative pain which if unrelieved may result in prolonged hospital stay, inability to participate in rehabilitation programs, poor outcomes, and greater use of health-care resources. Perioperative pregabalin improves postoperative outcomes after TKA (4). This study examines the effect of pregabalin administered perioperatively for TKA on pain-related neurotransmitter concentrations, intrathecal analgesic consumption and range of motion (ROM). Pregabalin effects on neurotransmitter concentrations may identify pathways by which α2δ binding by pregabalin reduces postoperative pain.

Objectives:

Primary Endpoint: Measure effect of pregabalin on spinal neurotransmitters after TKA Secondary Endpoint: Correlate changes in spinal neurotransmitters with pregabalin to improvements in patient outcomes after TKA (e.g. ROM).