The invention provides an assay for determining whether a test agent is a COX modulator. In general terms, the assay includes: determining whether a test agent modulates binding of a PDZ-containing polypeptide to a COX PL-containing polypeptide. The PDZ-containing polypeptide may contain the PDZ domain of PDZ domain of MAGI1, TIP-1, MAST2, PSD95, or SHANK. The assays may be done in a cell-free environment or in a cellular environment, particularly using a neuronal cell. The invention finds use in a variety of therapeutic applications, including for identifying agents for use in treating cancer, pain, inflammation and neuronal conditions caused by acute insult, e.g., stroke.