Abstract: The present invention is directed to analgesic Clostridial neurotoxin derivatives comprising polypeptides having a long-lasting SNARE protein-selective endopeptidase activity. These derivatives selectively bind to and are internalized by non-neuronal cells secreting cytokines or sensory neurons in preference to motor neurons or autonomic neurons. The invention is also directed to nucleic acid constructs encoding such polypeptides, and methods of making such derivatives and nucleic acid constructs, and methods of treating pain, such as chronic pain, by administering such derivatives to a patient suffering from, or at risk of suffering from such pain.