This paper will provide a literature review focused on the use of topical analgesic agents and modulation of treatment variables to decrease pain associated with Negative Pressure Wound Therapy (NPWT) dressing changes. The following PICO question was posed: "In patients receiving NPWT (P), what modalities can be utilized (I) to improve the patient's pain experience during dressing changes (O)?" Though NPWT is very effective and beneficial, the pain that accompanies dressing changes is significant and must be properly addressed to facilitate an environment of holistic patient care. Some facilities are lacking protocols for pain management in patients with wounds who have been prescribed NPWT, including both pharmacologic and non-pharmacologic means. Medline (OVID) and EBSCO Host were searched for relevant literature using keywords, "NPWT", "VAC", "PAIN", "ANALGESIA", "MANAGEMENT." Information from RCTs as well as evidence-based guidelines was synthesized, and evidence suggests that a combination of topical analgesia and modulation of treatment variables can serve to decrease the pain experience in patients undergoing NPWT. Using this information, a multi-modal pain management protocol can be created for NWPT-related pain.