Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors

6533b85bfe1ef96bd12bb669

RESEARCH PRODUCT

Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors

Tiziana Rubino Ken Mackie Claudiu Marian Rohini Kuner Sandor Batkai Gary J. Brenner Krisztina Monory Cristina E. Constantin Beat Lutz Pal Pacher Nitin Agarwal Peter W. Reeh Christoph W. Michalski Fumimasa Amaya Daniela Parolaro Michaela Kress Irmgard Tegeder Giovanni Marsicano Clifford J. Woolf Michael Fischer George Kunos

subject

Central Nervous System Cannabinoid receptor Cannabinoid Receptor Modulators medicine.medical_treatment Central nervous system Pharmacology Biology Article Mice Receptor Cannabinoid CB1 Ganglia Spinal Cannabinoid Receptor Modulators Peripheral Nervous System medicine Animals Neurons Afferent Alleles DNA Primers Mice Knockout Nerve Fibers Unmyelinated Cannabinoids General Neuroscience Nociceptors Peripheral Nervous System Diseases Endocannabinoid system Electrophysiology Mice Inbred C57BL medicine.anatomical_structure nervous system Peripheral nervous system Neuropathic pain Nociceptor lipids (amino acids peptides and proteins)Cannabinoid Analgesia Neuroscience

description

Although endocannabinoids constitute one of the first lines of defense against pain, the anatomical locus and the precise receptor mechanisms underlying cannabinergic modulation of pain are uncertain. Clinical exploitation of the system is severely hindered by the cognitive deficits, memory impairment, motor disturbances and psychotropic effects resulting from the central actions of cannabinoids. We deleted the type 1 cannabinoid receptor (CB1) specifically in nociceptive neurons localized in the peripheral nervous system of mice, preserving its expression in the CNS, and analyzed these genetically modified mice in preclinical models of inflammatory and neuropathic pain. The nociceptor-specific loss of CB1 substantially reduced the analgesia produced by local and systemic, but not intrathecal, delivery of cannabinoids. We conclude that the contribution of CB1-type receptors expressed on the peripheral terminals of nociceptors to cannabinoid-induced analgesia is paramount, which should enable the development of peripherally acting CB1 analgesic agonists without any central side effects.

year	journal	country	edition	language
2007-02-20

http://hdl.handle.net/11383/1676523