Patients with chronic wounds may experience persistent, debilitating pain that cannot be adequately managed with analgesics and that negatively impacts their quality of life. In this case series, three painful chronic and ischemic wounds that were caused by polyarteritis nodosa vasculitis (n = 1) and peripheral arterial disease (PAD) (n = 2) were successfully treated with cryopreserved umbilical cord tissue and/or amniotic membrane and umbilical cord particulate, resulting in notable reduction in pain within 7 days followed by expedited wound closure. No adverse events related to these tissue products were observed. These preliminary data demonstrate its safety and efficacy in reducing pain and promoting wound healing in painful chronic and ischemic wounds.