Abstract: Inhibition of EphB receptors (e.g., EphB1) can be used in therapeutic methods for treating EphB receptor-associated conditions (e.g., pain, cancer). Demeclocycline, chlortetracycline, and minocycline are identified as EphB receptor inhibitors. Accordingly, aspects of the disclosure relate to methods for treating pain comprising providing demeclocycline, chlortetracycline, minocycline, or derivatives thereof, alone or in combination, to an individual in need thereof. Further aspects relate to pharmaceutical compositions comprising two or more of minocycline, demeclocycline, chlortetracycline, and/or derivatives thereof.