Opioid Receptor Populations In Tolerance To Opiate Analgesia
Reference : PhD Claire GAVERIAUX-RUFF
Offer publication : April 5, 2016
Background: Opiates are potent analgesics used to treat severe pain. Opiates like morphine act through the activation of mu opioid receptor. The use of mu receptor-targeted opiates is often dampened by their side effects including tolerance to analgesia or dependence. A second opioid receptor, delta receptor, is presently under study for the development of novel analgesics and anxiolytics. Opioid receptors expressed by peripheral neurons were shown implicated in endogenous pain control and opiate analgesia, but the receptor populations that participate in analgesic tolerance have not been identified at the cellular level. Glial cells such as microglia and astrocytes are key cells for the development and maintenance of chronic pain. However the role of the opioid receptors expressed by glial cells in tolerance to opiate analgesia and opiate-induced hyperalgesia has
not been determined yet. Also, the role of glial opioid receptors in the control of social interactions or cognitive responses is unknown. More generally, the study of the role of genes in social behaviors in mice is still in its infancy.
Project: the project aims at investigating the role of the mu or delta opioid receptors expressed by glial cells (astrocytes and microglia) in the control of chronic pain, opiate analgesia and analgesic tolerance. The respective contributions of these receptor populations will be evaluated by the conditional
inactivation of these genes in mice. Novel mouse lines are generated to inactivate mu and delta opioid receptor genes in glial cells. Control global knockout and ‘floxed’ mouse lines have been characterized and are available in the laboratory. Analgesia and hyperalgesia will be measured in nociceptive tests on animals with or without induced inflammation or neuropathy. The comparison of analgesic responses in the different mouse lines
will enable to explore the contribution of these opioid receptor populations in the development and persistence of chronic pain, opiate analgesia and tolerance to analgesia.
The roles of glial opioid receptors in the control of social interactions or cognitive responses will be evaluated with behavioral tests already established or that will be developed. The student will be able to participate to the study of the role of other genes in these cognitive or social responses.
- WISHED SKILLS : The student will be highly motivated for the study of neuroscience and inflammatory pathologies. He/she must have a strong knowledge in cellular and molecular biology, in pharmacology as well as a basic knowledge on mouse behavioral responses. He/she will be interested in developing novel animal models, and more generally by genetic approaches in vivo. The student must show his/her interest for models of pathology and likes to work in a regular and organized manner.
- EXPERTISES WHICH WILL BE ACQUIRED DURING THE TRAINING : During his/her PhD training, the student will strengthen his/her skills in molecular biology, mouse genetics, pharmacology and neuroscience. He/she will acquire expertise in behavioural analysis of genetically modified animals. He/she will get familiar in cellular imaging and pharmacology of pain. He/she will benefit from a rich scientific and technical environment that
will help him/her develop his/her potential as a researcher and his/her communication skills.
Application Deadline : Dec. 31, 2016