Funding

To study the etiology and the epigenetic pathways leading to and regulating chronic itch. Similarly, to examine the mechanisms underlying skin changes, including epigenetic alterations while also testing the efficacy of medications, especially topical intervention. In this study, the investigators aim to examine chronic sensory disorder mechanisms related to chronic itch.

Itch was recently identified as one of the top three priority topics in dermatology at a Research Agenda Conference sponsored by the American Academy of Dermatology in 2012. Chronic itch is a complex phenomenon, involving the skin, immune and nervous systems to various degrees. Therefore, focusing on a particular pruritic disease will enable us to work out the underlying pathophysiological mechanisms that occur between the skin and the brain to establish a rational treatment approach.

Atopic Dermatitis (AD) is defined as a chronic inflammatory dermatological disease characterized by immunological and neurological cutaneous hyperreactivity with ongoing itch and inflammation. It is linked to an atopic predisposition with skin barrier abnormalities, recurrent delayed-type inflammations; frequently the development of IgE-mediated inhalant and gastrointestinal-related immediate type reactions. It is estimated that the prevalence for AD is at least 17% of the population lifetime worldwide with some reports of increasing prevalence in the last decades. It is also increasingly being observed in the aging population with dry, itchy skin.

Various topical and systemic therapies are available and choices are based on disease extent, presence of acute flare, and age of the patient. Unfortunately, itch in AD can be challenging to control; although multiple topical and systemic treatments are available, to date no universally accepted treatment exists.

The investigators have previously shown that opioid receptors play an important role in pruritus. Therefore, the investigators plan on expanding on previous and ongoing experiences with opioid antagonists and study the epigenetic and molecular mechanisms behind. Moreover, the investigators have recently discovered that the endogenous opioid ligand Met-Enkephalin influences circadian rhythm by binding directly to CLOCK gene promoters in the nucleus, which then change the amplitude and phase-shift these genes in keratinocytes.

Ultimately, the investigators would like to evaluate the effectiveness of topical application of Naltrexone in an effort to potentially help to treat chronic, untreatable itch and learn more about peripheral disorders of sensation (itch and pain).

Inclusion Criteria:

• Diagnosis of AD via simplified UK Working Group Criteria and a baseline PSGA score of 2 or greater
• Subjects taking hormone-containing medications must be on a stable dose for 6 months prior to study start to avoid any confounding influence on sensory and pain perception

Exclusion Criteria:

• Use of topical or oral anti-inflammatory medications for 2 weeks prior to the study start
• Use of topical or oral anti-histamines for 2 weeks prior to the study start
• Use of topical or oral anti-pruritic agents for 2 weeks prior to the study start
• Use of oral neuromodulatory agents for 2 months prior to study start
• Current use of chronic pain medications (including opioids, antidepressants and anti-epileptic drugs)
• Use of nicotine-containing products for the past 6 months prior to study start
• History of radiation or chemotherapy
• History of traumatic injury on prospective test sites
• Unstable thyroid function within the past 6 months prior to study start to exclude thyroid-related neuropathy (Duyff et al, 2000)
• Known history of central or peripheral nervous system dysfunction
• History of acute hepatitis, chronic liver disease or end stage liver disease
• History of human immunodeficiency virus (HIV) or acquired immune deficiency syndrome
• History of neuropathy associated with chronic obstructive pulmonary disease, diabetes mellitus, documented exposure to organophosphates or heavy metals or polychlorinated biphenyls
• Known nutritional deficiency (vitamin B12, vitamin D, iron or zinc) within 3 months prior to the study start
• Use of illicit drugs within the past 6 months prior to study start
• History of daily use of power tools
• Lyme disease, porphyria, rheumatoid arthritis, Hansen's disease (leprosy) or use of antineoplastic chemotherapeutic agents
• Subject has any medical condition that, in the judgment of the Investigator, would jeopardize the subject's safety following exposure to the administered medications