Prescription painkillers are the most common form of drug abuse. About 36 million people in the world are affected by opioid abuse. According to a study published in Cell Reports targeting delta opioid receptors in peripheral tissues instead of mu receptors in the brain might avoid pain killer abuse and side effects.
"People living with chronic pain have few innovative analgesic options available to them outside of systemic opioids. Prolonged use of these opioids can result in respiratory depression, tolerance, addiction, and overdose," says senior study author Nathaniel Jeske of the University of Texas Health Science Center at San Antonio. "Being able to increase the responsiveness of peripheral opioid receptor systems could lead to a reduction in systemic opioid administration, thereby reducing the incidence of side effects."
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Most clinical opioids currently available target mu opioid receptors, including those located in the brain, and therefore have a high potential for abuse. By contrast, drugs targeting delta opioid receptors in the peripheral nervous system rather than the brain and spinal cord produce fewer side effects in animals and have a much lower abuse potential. However, delta opioid receptors in peripheral tissues only become activated in the presence of inflammation. Because it has not been clear how to overcome this need for an inflammation trigger, the development of peripherally restricted drugs targeting delta opioid receptors has been limited.
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The findings expand the known function of GRK2 to include a role in inhibiting the function of delta opioid receptors in peripheral sensory neurons. Moving forward, the researchers will attempt to replicate the findings using human tissues. "By shedding light on how inflammation activates delta opioid receptors, this research could potentially lead to the development of safer, more effective opioids for the treatment of pain," Jeske says.
Source: Eurekalert
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