A single chain, polypeptide fusion protein, comprising: a non-cytotoxic
protease, or a fragment thereof, which protease or protease fragment is
capable of cleaving a protein of the exocytic fusion apparatus of a
nociceptive sensory afferent; a Targeting Moiety that is capable of
binding to a Binding Site on the nociceptive sensory afferent, which
Binding Site is capable of undergoing endocytosis to be incorporated into
an endosome within the nociceptive sensory afferent; 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; and a translocation domain
that is capable of translocating the protease or protease fragment from
within an endosome, across the endosomal membrane and into the cytosol of
the nociceptive sensory afferent. Nucleic acid sequences encoding the
polypeptide fusion proteins, methods of preparing same and uses thereof
are also described.