SFI UREKA Site in Molecular Recognition
Translating Design into Application

Biological Studies

Project 11:      Investigating the Role of Endocannabinoids and their Receptor Targets in Endogenous Pain Suppression

Supervisor:     Dr. David P. Finn, Department of Pharmacology and Therapeutics

Project Summary: 

The overall objective of Dr. Finn’s research is to increase understanding of the neurobiological mechanisms underlying the development and treatment of pain, inflammation, mood disorders and impaired cognition. His work is concerned with elucidating the role of a number of different receptor types (cannabinoid, opioid, adrenoceptor, imidazoline, serotonin, vanilloid, N-type Ca ²⁺ channels) in mediating and modulating behavioural, neurochemical and neuroendocrine responses relevant to pain, anxiety, depression and cognition. Pain is the most common reason people seek medical help and has an immense impact on health, society and the economy.  Detailed understanding of the physiology of nociception and the endogenous analgesic system is essential for development of improved analgesics.  Stress exerts a potent, but complex, modulatory influence on pain. Acute, intense stress/fear, suppresses pain (fear-induced analgesia) ^2,4.  In contrast, moderate, chronic stress/anxiety enhances pain (anxiety-related hyperalgesia) ⁵.  This bidirectional effect of stress on pain is observed in humans and rodents, however, the underlying neurobiological mechanisms are poorly understood. Our recent work, and that of others, has demonstrated a key role for the brain’s endogenous cannabinoid (endocannabinoid) system during pain- and fear-related behaviour ^1,3.  We have demonstrated that endocannabinoid-CB ₁ receptor signalling mediates fear-induced analgesia in rats ^1,3.  Our pilot data implicate the amygdala, hippocampus and periaqueductal grey, but further work is required to investigate the role of these and additional brain structures and to elucidate the precise neurochemical and molecular mechanisms. Furthermore, the role of the endocannabinoid system in anxiety-related hyperalgesia has not yet been investigated.  This project will advance understanding of the neurobiology underpinning stress-induced modulation of pain and may uncover new therapeutic targets for the treatment of pain, anxiety and their co-occurrence.  All experimental procedures on living rats will be carried out under licence from the Department of Health and Children in accordance with the Cruelty to Animals Act, 1876 (SI 17/94) and EU Directive 86/609 and following approval by the Animal Care and Research Ethics Committee at NUI, Galway.

The student will work closely with a senior researcher and will be involved in all aspects of the study from experimental design and execution to data analysis and presentation. Specifically, they will gain expertise in behavioural neuropharmacology, animal husbandry, computer-assisted assessment of rodent pain- and anxiety-related behaviour, statistical analysis and oral and written presentation of data. They will be fully integrated into the research team for the duration of the project. The full repertoire of expertise and facilities in Dr Finn’s research group/lab will be at the student’s disposal and they will benefit from intensive exposure to the integrative whole-systems neuroscience approach employed in the lab.

References : [1]. Finn, et al. (2004) Eur J Neurosci 20, 848-852.; [2] Ford and Finn (2008) Pain 140(1):3-7; [3] Butler et al. (2008) Pain 140(3):491-500; [4] Butler and Finn (2009) Prog Neurobiol 88(3):184-202; [5] Imbe et al. (2006) Front Biosci. 11: 2179-2192.

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