Regulation of Kappa opioid receptor-mediated signaling and peripheral analgesia

Project: Research project

Project Details


Abstract/Summary Pain affects more Americans than does diabetes, heart disease and cancer combined. Opioids are a key
drug class for pain treatment, however, there are significant drawbacks (e.g. CNS adverse effects, social and
legal issues) that limit their use for effective management of pain. Consequently, development of novel
approaches for improved pain control is a critically important research objective. To eliminate adverse CNS-
derived effects, attention has turned to targeting peripherally located opioid receptors expressed on the pain-
sensing neurons themselves. Importantly, the regulatory mechanisms of opioid receptor systems in peripheral
sensory neurons are unique, and results obtained from studies in other systems (CNS, heterologous expression
systems, etc.) do not always translate to peripheral sensory neurons. Thus, to understand opioid receptor
function in peripheral sensory neurons, experiments must be done with peripheral sensory neurons. The goal of this project is to study the regulation of kappa opioid receptor (KOR) signaling systems in
peripheral sensory neurons, using primary cultures of adult rat sensory neurons and a behavioral model of
nociception. Our specific aims are 1) To delineate the role of ERK in regulation of KOR function in peripheral
sensory neurons; 2) To delineate the role of JNK in regulation of KOR function in peripheral sensory neurons;
and 3) To delineate the role of acute desensitization in regulating KOR agonist efficacy in peripheral sensory
neurons. Our overall goal is to increase the reliability and therapeutic efficacy of peripherally-restricted kappa
opioid analgesic drugs. By understanding the cellular mechanisms that are involved in regulating the
responsiveness of kappa opioid receptor systems on peripheral sensory neurons, improved approaches to treat
pain can be developed that have improved therapeutic efficacy and are devoid of debilitaing CNS-mediated
adverse effects. The combination of rigorous mechanistic studies using primary sensory neurons in culture
with the translational value of behavioral studies provides a powerful approach to understanding the
regulation kappa opioid receptor agonist efficacy in a physiologically relevant system and may lead to new
approaches for improved pharmacotherapy for pain.
Effective start/end date1/15/1411/30/17


  • National Institutes of Health: $279,536.00
  • National Institutes of Health: $99,640.00
  • National Institutes of Health: $279,536.00
  • National Institutes of Health: $279,536.00


  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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