Patient case (clinical description): A 47-year-old woman comes to the office complaining of pain in the calf and knee when she bends down. The pain limits her activity. Her medical history is significant for osteoarthritis, for which she uses nonsteroidal anti-inflammatory drugs (NSAIDs) for the past two years. She is living with her husband and has 3 children. She doesn't smoke but drinks alcohol occasionally. Her vital signs are normal. On physical examination, there is a small effusion in the right knee. The effusion grew a little larger and she developed a tender swelling in the popliteal fossa and calf. Both the pain and swelling worsened as she bent and straightened her knee.

Patient's own account: I'm a 47-year-old woman, married with 3 kids. I don't smoke and I drink occasionally. I went to the doctor because of pain in my calf and knee when I was bending down. This has been limiting my daily activities. I have been diagnosed with osteoarthritis for which I have taken anti-inflammatory drugs for the past 2 years. The doctor saw a small fluid buildup in my right knee. This buildup became a bit bigger and I have a swollen calf. The pain is worse when I bend and straighten my knee.

Clinical trial: Milnacipran for Chronic Pain in Knee Osteoarthritis

Eligibility criteria:
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)
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 90 Years

Eligibility (NLI label): Entailment