Compositions and methods for treating and preventing headaches

A composition comprising:

• a) a target cell binding unit;
• b) a pore-forming unit,
• c) a rigid synthetic linker linking the target cell binding unit and the pore-forming unit, and
• d) a payload unit comprising the agent, wherein said payload unit binds non-covalently to a pore formed by the pore-forming unit upon activation and oligomerization of the pore-forming unit, wherein the payload unit has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:
• 2;
• wherein the pore-forming unit is a polypeptide derived from a first AB type of non-neurotoxic binary toxin, and wherein the target cell binding unit is a polypeptide derived from a second AB type of toxin, said second AB type being different from the first AB type, wherein the target cell binding unit binds to a neural cell,
• wherein the target cell binding unit and the pore-forming unit are covalently linked through the rigid synthetic linker to form a polypeptide.