Study to Evaluate the Efficacy of Milnacipran in the Treatment of Pain Due to Osteoarthritis

Inclusion Criteria: * Be 21-75 years of age and in good general medical and psychological health * Be able to speak, read, write, and understand English, understand the consent form, complete study related procedures, and communicate with the study staff * Have a negative urine pregnancy test at screening, and use appropriate birth control * Have documented painful Osteoarthritis (OA) of at least one knee for at least 6 months; OA should be of Class I-III and meet the American College of Rheumatology (ACR) clinical classification criteria, defined as: 1. Knee pain and at least 3 of the following 6: * Age \> 50 * Morning stiffness \< 30 minutes * Crepitus on active motion * Bony tenderness * Bony enlargement * No palpable warmth of synovium 2. The target joint must not contain any type of orthopedic and/or prosthetic device * Have a target joint pain average of 5 days per week and have an average pain intensity of at least 4/10 on the 0-10 NRS over the last 24 hours prior to screening * Have stable treatment modalities, e.g. acupuncture, physical therapy * Be willing to stop taking Non-steroidal Anti-inflammatory drugs (NSAIDs) and opioids for the duration of the study Exclusion Criteria: * Are allergic or intolerant to SNRI; have a previous poor response to a SNRI for OA pain; are currently taking an SNRI or tricyclic antidepressant * Have a body mass index (BMI) \>40 kg/m2 * Have an Hospital Anxiety and Depression Scale (HADS) score \>12 on either subscale or has an established history of major depressive disorder not controlled with medication * Have significant pain outside the target knee, including significant hip or back pain. (Bilateral knee OA allowed.) * Have pain affecting the target knee that is due to any other etiology than OA * Have documented history of inflammatory arthritis including rheumatoid arthritis * Have had local injections in target joint within the past 3 months prior to screening * Have had oral or intramuscular corticosteroids within the past 30 days * Have had worker's compensation claim, disability, or litigation * Have a known history of uncontrolled narrow-angle glaucoma * Have a known history of suicidal ideation * Use monoamine oxidase inhibitors (MAOI) concomitantly * Are allergic or intolerant to acetaminophen * Using opioids 4 or more days per week during the month preceding the screening visit * Have significant history or renal impairment/failure.