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CB1 expression in DRGs

CB1 expression in DRGs. (Pertwee 2009). Pharmacological tools. Selectivity and affinity of CB1 agonists are suboptimal. DRG. Spinal cord. (Agarwal et al 2007). CB1-mediated nociception. Sensory neurons specific CB1 KO. Expression in DRG. Expression in brain. (Agarwal et al 2007).

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CB1 expression in DRGs

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  1. CB1 expression in DRGs

  2. (Pertwee 2009) Pharmacological tools Selectivity and affinity of CB1 agonists are suboptimal

  3. DRG Spinal cord (Agarwal et al 2007) CB1-mediated nociception Sensory neurons specific CB1 KO

  4. Expression in DRG Expression in brain (Agarwal et al 2007) CB1-mediated nociception Sensory neurons specific CB1 KO

  5. Nociceptive response (acute pain) and locomotor performance (Agarwal et al 2007) CB1-mediated nociception

  6. Nociceptive response (inflammatory pain) (Agarwal et al 2007) CB1-mediated nociception

  7. Effect of WIN55212-2 on inflammatory pain (Agarwal et al 2007) CB1-mediated nociception

  8. Effect of intrathecal vs intraplantar administration of WIN55212-2 (Agarwal et al 2007) CB1-mediated nociception

  9. CB1-induced nociception: mechanism of action • Two potential sites of action: • DRG: nociception • CNS: processing of nociceptive information • Action on DRG blocks pain transmission to the CNS • Action on the CNS may modulate nociceptive input elaboration

  10. CB2-mediated nociception

  11. (Beltramo 2009) CB2 synthetic agonists Bicyclic cannabinoid: HU308 (1) Cannabinor (2) THC derivatives: JWH133 (3) Aminoalkylindoles: AM1241 (4) L768242 (5) A-796260 (6) Pyrimidine derivatives: GW842166X (7) Thiazole derivatives: A-836339 (8) Carboxiamide derivatives: Taisho (9) Thiazine derivatives: Shonogi (10)

  12. (Hanuš et al 1999) CB2-mediated nociception

  13. AM1241 (Ibrahim et al. 2003) CB2-mediated nociception Effect on neuropathic pain

  14. Sham-operated wt Spinal nerve ligated wt Spinal nerve ligated CB1 KO Sham-operated CB1 KO (Ibrahim et al. 2003) CB2-mediated nociception Effect on neuropathic pain

  15. Reduction of mechanical allodynia in SNL rat (Beltramo et al. 2006) CB2-mediated nociception Effect on neuropathic pain

  16. AM1241 antihyperalgesic effect in μ-opiod receptor wt and KO mice Release from paw skin (Ibrahim et al. 2006) CB2-mediated nociception:cellular mechanisms

  17. Expression in spinal cord (Zhang et al 2003) CB2 localization

  18. CB2 in situ hybridization in the dorsal horn Ipsilateral Contralateral CB2 OX42 CB2 (Zhang et al. 2003) CB2 localization

  19. Summary and perspectives • The cannabinoid system play an important role in nociception • The research to develop a cannabinoid analgesic has made significant progress • CB2 agonist and mixed peripherally restricted agonists are at present the most promising strategies • Research on the inactivation system is progressing and show interesting potential • Side effects and regulatory constrain remain important issues to be solved

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