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.