Effective treatments of acute pain for extended periods of time are provided. The treatments include the administration of one or more drug depots at or near a target site wherein the drug depots include an effective amount of clonidine formulated within a polyorthoester. By administration of one or more drug depots at or near the target site, one can relieve pain caused by diverse sources, including but not limited to spinal disc herniation (i.e. sciatica), spondilothesis, stenosis, discongenic back pain and joint pain, as well as pain that is incidental to surgery. In some embodiments, the relief can be for at least twenty-five days, at least fifty days, at least one hundred days or at least one hundred and thirty-five days.