Milnacipran for Chronic Pain in Knee Osteoarthritis

Inclusion Criteria: * Knee pain and osteophytes on radiographs OR * Knee pain plus patient age of 40 years or older, morning stiffness lasting 30 minutes or less, and crepitus (cracking sound) during motion * Experiences chronic pain for 6 months or longer * Average pain rating of worse knee is equal to 4 or greater on a 0-10 scale * If female, is not pregnant or breast feeding, and not currently attempting to conceive; if of childbearing potential, use of a highly effective method of birth control (as determined by Pl) * Able to walk at least ½ a city block a day, and agrees to try and slowly increase that over the course of study * Able to read and speak English and provide informed consent * Able to understand and comply with all data collection methodology including electronic diary * Subject agrees to 1) continue their stable drug regimen with no changes during the course of study, 2) only use Tylenol 325 mg of tablets (a maximum of 8 tablets a day) for breakthrough pain, and 3) not use Tylenol or any other pain medicines 12 hours before testing. Exclusion Criteria: * Subject takes SNRIs (Savella, Cymbalta, Venlafaxine) or other neuroamine re-uptake blockers for mood disorders * Subject is allergic to SSRIs, SNRIs, or milnacipran * Subject has severe or untreated psychiatric disturbance (e.g. mania, depression, anxiety, substance dependence) * Subject is medicated with 'triptans, MAOIs, SSRIs, other SNRIs, tricyclic or heterocyclic antidepressants, lithium, epinephrine, norepinephrine, clonidine or digoxin during the trial * Subject has a clinical diagnosis of fibromyalgia * Subject has severe ongoing or unaddressed medical conditions (e.g. Renal or Hepatic disease \[creatinine\>1.5 ml/dl; AST or ALT\> 3x normal limit\], uncontrolled hypertension, severe cardiac rate or rhythm disorders, rheumatologic disease (e.g. polymyalgia rheumatica), narrow angle glaucoma, hyponatremia, clotting disorders, uncontrolled seizure disorder or urinary retention) * Subject has cardiac implants * Subject has a knee replacement * Subject plans to start new pain treatments or therapies during the study (e.g. new pain medication, injections, PT, surgery)