Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors.
Nat Neurosci. 2007-06-10; 10(7): 870-879
DOI: 10.1038/nn1916
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1. Nat Neurosci. 2007 Jul;10(7):870-9. Epub 2007 Jun 10.
Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid
receptors in nociceptors.
Agarwal N(1), Pacher P, Tegeder I, Amaya F, Constantin CE, Brenner GJ, Rubino T,
Michalski CW, Marsicano G, Monory K, Mackie K, Marian C, Batkai S, Parolaro D,
Fischer MJ, Reeh P, Kunos G, Kress M, Lutz B, Woolf CJ, Kuner R.
Author information:
(1)Institute for Pharmacology, University of Heidelberg, Im Neuenheimer Feld,
Heidelberg, 69120 Germany.
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.
DOI: 10.1038/nn1916
PMCID: PMC2234438
PMID: 17558404 [Indexed for MEDLINE]