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Unraveling the Potential of CB2 Receptor in Pain Management

Delve into the exploration of the CB2 receptor's role in neuronal function and pain management, presenting new avenues for therapeutic interventions and innovative research goals. Discover how cannabinoids could revolutionize pain therapies.

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Unraveling the Potential of CB2 Receptor in Pain Management

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  1. Cannabis: A journey from college to bench to bedside Ken Mackie (IUB) Michael Vasko (IUSM)

  2. Pain therapies • Inadequately-treated chronic pain is a major clinical problem • Current behavioral and pharmacological approaches: limited efficacy • Need for better therapies • Cannabinoids as novel pain therapeutics: • Cannabinoids = active components of cannabis (e.g., THC)

  3. Cannabinoids • Analgesic efficacy similar to codeine • Actions fundamentally different from opiates • Cellular site of action > 2 receptors • CB1 > well studied, analgesia, but psychoactivity • CB2 > little studied, analgesia, no psychoactivity • Therapeutic approaches: • Ligands to activate cannabinoid receptors • Enzyme inhibitors to increase endogenous ligands (endocannabinoids)

  4. Goals of our study (1) • What does CB2 do in neurons? • CB1 inhibits neurotransmitter release • Will CB2 receptors do the same? • CB2 is highly inducible • Therapeutically beneficial(?) • How to study function? • Introduce into cultured neurons • Deliverable 1: Will CB2 inhibit neurotransmission in vivo? Maresz et al. J. Neurochem. 95 (2005) 437-45

  5. Goals of our study (2) • What is the in vivo role of CB2? • Deliverable 2: Develop lentiviral tools to over express and knock down CB2 expression in sensory neurons • Deliverable 3: Will over expression of CB2 decrease pain? • Deliverable 4: Will knockdown of CB2 increase pain?

  6. Bodor et al, 2005 (layer V) Will CB2 inhibit neurotransmission in vivo? • Background: • CB1 receptors inhibit neurotransmission • Approach • Culture neurons from CB1 KO mice • Express CB2 receptors in these neurons • Examine neurotransmission • Exogenous cannabinoids • Endogenous cannabinoids

  7. Summary • CB2 receptors in neurons can inhibit neurotransmission • Presynaptic site of action • Tools have been made to over express and knockdown CB2 expression in vivo • Next – test and demonstrate efficacy with in vivo models

  8. Acknowledgements • Funding: RR025761, DA021696, and DA011322 • LMIC • Brady Atwood

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