Fusion proteins

A method of treating or ameliorating pain in a subject, comprising administering to said subject a therapeutically effective amount of a polypeptide fusion protein comprising:

• a. a non cytotoxic protease, or a fragment thereof, which protease or protease fragment cleaves a protein of the exocytic fusion apparatus of a nociceptive sensory afferent;
• b. a Targeting Moiety that binds to a Binding Site on the nociceptive sensory afferent, which Binding Site endocytoses to be incorporated into an endosome within the nociceptive sensory afferent;
• c. a protease cleavage site at which site the fusion protein is cleavable by a protease,
• wherein the protease cleavage site is located between the non cytotoxic protease or fragment thereof and the Targeting Moiety;
• d. a translocation domain that translocates the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent;
• wherein the Targeting Moiety is selected from the group consisting of BAM, β endorphin, bradykinin, substance P, dynorphin and/or nociception;
• wherein said polypeptide fusion protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
• 24, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 111, 112, 113, 115, 116, 120, 121, 124, 125, 126, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, and/or 157.