Clostridial toxin derivatives able to modify peripheral sensory afferent functions

A single chain polypeptide fusion protein comprising:

• (a) a targeting moiety (TM) that binds the polypeptide to a nociceptive afferent neuron by binding of said TM directly to a nociceptive afferent neuron or by binding of said TM to a ligand or to ligands that bind to a nociceptive afferent neuron;
• (b) a clostridial neurotoxin light chain (L-chain) or fragment thereof that is selected from a first clostridial neurotoxin serotype, wherein said L-chain or fragment thereof has protease activity specific for components of the neurosecretory machinery;
• (c) a clostridial neurotoxin heavy chain (H-chain) or fragment thereof that is selected from a second clostridium neurotoxin serotype;
• and
• (d) a site for cleavage by a proteolytic enzyme, wherein said cleavage site allows proteolytic cleavage between said L-chain or fragment thereof and H-chain or fragment thereof;
• wherein said H-chain or fragment thereof introduces said L-chain or fragment thereof into the cytosol of a nociceptive afferent neuron;
• and
• wherein said H-chain or fragment thereof lacks a functional C-terminal part of a clostridial neurotoxin heavy chain designated HC from one or both of said first or second clostridial neurotoxin serotypes.