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

  title={Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors},
  author={Nitin Kumar Agarwal and P{\'a}l Pacher and Irmgard Tegeder and Fumimasa Amaya and Cristina E. Constantin and Gary J Brenner and Tiziana Rubino and Christoph W Michalski and Giovanni Marsicano and Krisztina Monory and Ken Mackie and Claudiu Marian and Sandor Batkai and Daniela Parolaro and Michael J. M. Fischer and Peter W. Reeh and George Kunos and Michaela Kress and Beat Lutz and Clifford J. Woolf and Rohini Kuner},
  journal={Nature Neuroscience},
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… 
Mode of action of cannabinoids on nociceptive nerve endings
The cannabinoid receptor family currently includes two cloned metabotropic receptors: CB1, CB2 and possibly GPR55 which are distributed widely across many key loci in pain-modulating pathways, including the peripheral terminals of primary afferents.
Targeting the cannabinoid system to produce analgesia.
In addition to targeting cannabinoid receptors directly, protection of endocannabinoids (eCBs) from metabolism also produces analgesic effects, and reports that noxious stimulation elevates levels of eCBs in the spinal cord and brain provide further rationale for this approach.
Cannabinoid Receptor Mediated Analgesia: Novel Targets for Chronic Pain States
Reports that noxious stimulation elevates levels of endocannabinoids in the spinal cord and brain provide further rationale for this approach, and the effects of inhibition of fatty acid amide hydrolase on nociceptive responses in models of inflammatory and neuropathic pain are discussed.
The cannabinoid agonist CB-13 produces peripherally mediated analgesia in mice but elicits tolerance and signs of CNS activity with repeated dosing
Significant caution is warranted regarding therapeutic use of CB-13 with the goal of avoiding CNS side effects, but the clear analgesic effect of acute peripheral CB1 receptor activation suggests that peripherally restricted cannabinoids are a viable target for novel analgesic development.
The endocannabinoid system and pain.
The roles of anandamide and 2-arachidonoylglycerol, released under physiological conditions, in modulating nociceptive responding at different levels of the neuraxis will be emphasized in this review.
Involvement of cannabinoid type 1 receptor in fasting-induced analgesia
The results suggest that both peripheral and central CB1Rs contribute to fasting-induced analgesic effects and the CB1R in the GI system which transmit fasting signals to the brain, rather than those in the peripheral sensory neurons, may contribute to fasted-induced opioid effects.
Targeting the cannabinoid system for pain relief?
  • L. Chiou, S. Hu, Y. Ho
  • Biology, Chemistry
    Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists
  • 2013
Endocannabinoid metabolism and uptake: novel targets for neuropathic and inflammatory pain
Recent studies of the effects of inhibition of metabolism of endocannabinoids versus uptake of endOCannabinoids on nociceptive processing in models of inflammatory and neuropathic pain are reviewed.


An analgesia circuit activated by cannabinoids
It is shown that a brainstem circuit that contributes to the pain-suppressing effects of morphine is also required for the analgesic effects of cannabinoids, and that cannabinoids are indeed centrally acting analgesics with a new mechanism of action.
Cannabinoid mechanisms of pain suppression.
Evidence supporting a role for cannabinoids in suppressing pain at spinal, supraspinal, and peripheral levels is examined and the potential of exploiting cannabinoid antinociceptive mechanisms in novel pharmacotherapies for pain is discussed.
Inhibition of Inflammatory Hyperalgesia by Activation of Peripheral CB2 Cannabinoid Receptors
The results suggest that peripheral CB2 receptors may be an appropriate target for eliciting relief of inflammatory pain without the CNS effects of nonselective cannabinoid receptor agonists.
The role of central and peripheral Cannabinoid1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain.
Cannabinoids are highly potent and efficacious antihyperalgesic agents in a model of neuropathic pain and are likely to be mediated via an action in the CNS and in the periphery.
Topical cannabinoid antinociception: synergy with spinal sites
Role of endogenous cannabinoids in synaptic signaling.
The synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation, and the fine-grain anatomical distribution of the neuronal cannabinoid receptor CB1 is described in most brain areas, emphasizing its general presynaptic localization and role in controlling neurotransmitter release.
Peripheral opioid analgesia.