Designer Drugs and Neuron Transplants: Potential Treatments for Pathologic Chronic Pruritus

Writing this post made me itchy, read with caution.

Itches are a curious and strange phenomenon. While conducting observational research on zoo animals, I noticed many of them displaying similar scratching behaviors to what humans have when we feel a sudden, random itch. After thinking for a while, I wondered if perhaps non-pathologic itches maintained some physiological or evolutionary purpose, and thought maybe idiopathic, non-pathologic itches are one way that our nervous systems might perform “maintenance” on our nerve function and our bodies, or bring our attention to parts of our body. But beyond this little idea is the real issue of pathologic itching, or pruritus, in clinical settings.

Pathologic itching is currently a major clinical challenge that severely decreases the quality of life for around 1/5th of patients suffering from various systemic disorders, including ESRD, chronic liver disease, atopic dermatitis, MS, and neuropathy (Garibyan, Rheingold, & Lerner, 2013) (Callahan and Lio, 2012). This is an issue because the presence of co-morbid pruritus is linked to an increase in mortality rates compared to non-itching populations with these disorders (Garibyan, Rheingold, & Lerner, 2013). According to a paper by Callahan and Lio, pathologic itching can be classified as either acute or chronic. Currently, antihistamine treatments are effective in treating acute itching, working to counteract histamine-mediated responses transmitted by C-fibers in the skin. The real issue lies in chronic itching, which anti-histamines (and practically all other treatments) are ineffective in treating long term. There is very little understanding of the physiological mechanisms of chronic pruritus, but a recent study may shine a light in the right direction. Researchers Kanehisa et Al. found that when a population of mice was low in BHLBH5 transcription factor, they displayed increased chronic itch-behavior phenotypes. This suggests that chronic itch may result from a loss of SDH (neuronal circuit) inhibitory interneurons caused by this deficiency. In this study, these mice populations received transplants of embryonic γ-aminobutyric acid (GABA)-ergic precursor neurons that expressed hM3Dq receptors into their SDH. Using DREADD designer drug technology, the researchers used CNO, or clozapine-N-oxide, to activate the hM3Dq receptors in the neuronal cells, enabling a release of GABA that suppressed the itching behaviors in the mice. These is still much unknown about how chronic pruritus works, but this research is a strong step in understanding how pathologic itching works and may lead to potential treatments. Further research is needed before any treatments can be brought into clinical settings.

Cited Sources:

Callahan, S. W., & Lio, P. A. (2012). Current Therapies and Approaches to the Treatment of Chronic Itch. Current Medical Literature: Dermatology, 17(2), 29–40. Retrieved from http://dml.regis.edu/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=aph&AN=77950126&site=ehost-live&scope=site

Garibyan, L., Rheingold, C. G., & Lerner, E. A. (2013). Understanding the pathophysiology of itch. Dermatologic therapy, 26(2), 84-91.

Kanehisa, K., Shiratori-Hayashi, M., Koga, K., Tozaki-Saitoh, H., Kohro, Y., Takamori, K., & Tsuda, M. (2017). Specific activation of inhibitory interneurons in the spinal dorsal horn suppresses repetitive scratching in mouse models of chronic itch. Journal of Dermatological Science, 88(2), 251-254. doi:10.1016/j.jdermsci.2017.05.017