Systems and methods apply a selected treatment agent or agents into contact with tissue at or in the region of a dysfunctional sphincter (in the case of GERD, fecal incontinence, or other dysfunctional sphincter disorders) to affect improved sphincter barrier function and/or to disrupt abnormal nerve pathways. The treatment agent can include at least one cytokine and/or at least one tissue bulking agent and/or at least one vanilloid compound to evoke a desired tissue response. The systems and methods can be used a primary treatment modality, or applied as a supplementary treatment before; during or after a primary intervention.