Fusion proteins and methods for treating, preventing or ameliorating pain

A single chain polypeptide fusion protein, comprising:

• a non-cytotoxic protease capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent;
• a galanin-targeting moiety that binds to a binding site on the nociceptive sensory afferent, the binding site capable of incorporating into an endosome within the nociceptive sensory afferent;
• a protease cleavage site at which site the fusion protein is cleavable by a protease;
• a translocation domain capable of translocating the protease from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory
• a first spacer located between the non-cytotoxic protease and the protease cleavage site, the first spacer comprising an amino acid sequence of from 4 to 25 amino acid residues;
• and
• a second spacer located between the galanin-targeting moiety and the translocation domain, the second spacer comprising an amino acid sequence of from 4 to 35 amino acid residues;
• wherein:
• the protease cleavage site is located between the non-cytotoxic protease and the galanin-targeting moiety, and
• the galanin-targeting moiety is located between the protease cleavage site and the translocation domain.