Functional testing and pre-to post pain measure outcomes in chronic knee osteoarthritis pain with milnacipran: interim analysis of a randomized, double-blind, placebo-controlled trial

Abstract

Knee osteoarthritis is a chronic disease that affects twenty-seven million Americans and can cause significant stiffness and pain. Chronic pain is associated with structural changes and sensitization within the peripheral and central nervous systems. Serotonin norepinephrine reuptake inhibitors (SNRIs) are thought to modulate central sensitization. Milnacipran is a SNRI with greater selectivity for norepinephrine over serotonin reuptake inhibition. The hypothesis that functional testing would show improved performance and decreased pre-to posttest pain in subjects treated with milnacipran as compared to placebo was evaluated. Interim analysis of data collected during a single-site pilot phase IV randomized, double-blind placebo-controlled trial of milnacipran in a chronic knee osteoarthritis model was performed. Twenty-five subjects with a diagnosis of knee osteoarthritis were randomly assigned to milnacipran 200mg (n=17) or placebo (n=8) in a 2:1 ratio. Subjects were interviewed and tested at their visits during enrollment, completion of placebo lead-in phase, and at conclusion of the eleven week study. Functional testing included stair climb, treadmill, sit-to-stand, and finger-to-floor testing. Pain was assessed using a numeric rating scale (NRS) before and after each functional test. Milnacipran did not show statistically significant differences from placebo in treadmill, sit-to-stand, and finger-to-floor testing throughout all three visits. A statistically significant decrease in pre-to posttest pain (p=0.026) was found with subjects taking placebo as compared to milnacipran during stair climb testing at the concluding visit; all other stair climb pain ratings showed no statistically significant differences between placebo and milnacipran. These preliminary findings suggest that milnacipran does not significantly affect functional performance or pre-to posttest pain in a chronic knee osteoarthritis model. Further study is needed on the methodology of pain ratings during functional testing and the effects of milnacipran on chronic pain conditions. Supported by a grant from Forest Research Institute.