Itch can be painful.

Whether the cause is fleas, allergies, or skin problems, the animal suffers.  Unlike pain, the itch sensation evokes ascratching response instead of withdrawal behavior. However, itch and pain sensations share many similarities. Like chronic pain, chronic itch is a major clinical problem that affects quality of life (Sun et al., 2007, 2009).

Two products are in the pipeline that have been published by independent researchers to eliminate itch.

Bombesin-SAP,  Bombesin peptide attached to the ribosome-inactivating protein, saporin.  Bombesin is a 14-amino-acid peptide found in frog-skin.  Bombesin-SAP specifically targets GRP receptor-positive cells (Figure 1).  All other cells are left untouched. Elimination of cells expressing GPR receptor is useful in studying the role of bombesin in itch and eating behaviors.

• Sun YG, Chen ZF (2007) A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. Nature 448(7154):700-703.
• Sun YG, Zhao ZQ, Meng XL, Yin J, Liu XY, Chen ZF
  (2009), Cellular Basis of Itch Sensation.
  Science 325(5947):1531-1534.

SSP-SAP, a conjugation of saporin and SSP, the Sar⁹, Met(O₂)¹¹ analog of Substance P.  This specific analog of Substance P resists peptidase digestion, allowing a greater diffusion from the injection site before its metabolism.  SSP-SAP eliminates cells expressing the Substance P (NK-1) receptor.

The itch signal is passed through the superficial dorsal horn.  Carstens et al. (2010) investigated whether ablation of NK-1 receptor-expressing neurons in this area would affect itch-related scratching behavior. Rats received 20 µl of 2.27-µM SSP-SAP as an intracisternal injection.  The reduction in itch response to intradermal 5-hydroxytryptamine indicates that NK-1 receptor-expressing superficial dorsal horn neurons are important for spinal itch transmission.

Chronic itch is caused by increased sensitivity of itch-signaling pathways. It can be generated by normally itchy stimuli (hyperknesis) and by normally non-itchy light touch (alloknesis).  Akiyama et al. (2015) used an ovalbumin-induced atopic dermatitis model to study chronic itch in mice.  The mice received 400-ng intrathecal injections of Bombesin-SAP, SSP-SAP, or  control.  While Bombesin-SAP significantly attenuated hyperknesis, it had no effect on spontaneous scratching or alloknesis.  SSP-SAP reduced all behavioral signs of chronic itch.

• Carstens EE, Carstens MI, Simons CT, Jinks SL (2010) Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats. Neuroreport 21:303-308.
  
• Akiyama T, Nguyen T, Curtis E, Nishida K, Devireddy J, Delahanty J, Carstens MI, Carstens E. (2015) A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch. Pain 156(7):1240-1246.