A Relation of Morphine-induced Itch and Pain Processing

A Mechanistic Study on Morphine-induced Orthogonal Neural Plasticity for Itch and Pain Processing in Humans (a Relation of Morphine-induced Itch and Pain Processing)

In This experiment, the investigators would like to test the two following hypotheses regarding the mechanisms by which opioids cause itch:

1. Opioids cause itch by a spinal disinhibition mechanism (central nervous system (CNS) effect).
2. Opioids cause itch through a mast cell-destabilizing effect leading to release of histamine and tryptase in the skin where itch is evoked (peripheral mechanism).

Intrathecal and orally administered opioids are heavily used for the treatment of several acute pain conditions. However, while opioids are effective analgesics for acute pain, they are well-known to frequently cause itch (pruritus) as a side effect according with the two hypotheses stated above. So far, these two hypotheses have never been tested in humans.The present study describes a proposed study design for the purpose of confirming these two hypotheses in parallel in human subjects.

Primary endpoints of the study:

To evaluate changes itch and pain perception, and superficial perfusion after each itch provocations.

Secondary endpoints of the study:

To evaluate the existence of a correlation between itch sensitization and analgesic efficacy.

Inclusion Criteria:

• Healthy men and women in the age of 20-65 years
• The participants must be able to speak and understand English

Exclusion Criteria:

• Participants with any clinically significant abnormalities that in the opinion of the investigator may increase the risk associated with trial participation or may interfere with the interpretation of the trial results.
• Pregnant or lactating female persons
• Drug addiction defined as the use of cannabis, opioids or other drugs
• Previous or present neurologic, musculoskeletal or mental illnesses
• Current pain and itch causing diseases or psychiatric disorders
• Participants unable to understand or follow the instructions
• Participating in another study where investigational drug is used
• Participants had known allergy/discomfort to morphine
• Lack of ability to cooperate