Medications commonly used to treat osteoarthritis (OA) pain remain ineffective or poorly tolerated. Anti-depressant medications can also be used to treat pain and have recently been trialled in people with knee OA. While promising, the specific medication tested (Duloxetine) is not subsidised in New Zealand and its effects are not consistent across individuals – some people experience substantial pain relief while others receive no benefit. This study aims to compare the effectiveness of Duloxetine to a similar, cheaper medication called Venlafaxine for the treatment of knee OA pain. In addition, we will test the function of specific pain pathways before treatment, to see if we can predict which individuals will benefit most from these medications. Findings from this research may provide evidence for a new medication in the treatment of OA pain and allow doctors to better individualise pain treatment, matching medications to the underlying cause of a person's pain.