Increasing 2-AG levels in the anterior cingulate cortex attenuated fear-conditioned analgesia in rats, an effect blocked by a CB2 receptor antagonist but not a CB1 antagonist.
Pain researchers, neuroscientists studying the endocannabinoid system
CB2 (not CB1) receptors mediated the 2-AG effect on fear-conditioned analgesia in the cortex
What the researchers found
MGL inhibition (increasing 2-AG) in the ACC attenuated fear-conditioned analgesia. This effect was blocked by the CB2 antagonist AM630 but not the CB1 antagonist AM251. The CB2 antagonist alone reduced pain behavior in non-fear-conditioned rats. Both CB1 and CB2 receptor mRNA were confirmed in the ACC.
Why it matters
Understanding how the brain's own pain-suppression systems work through the endocannabinoid system could reveal new therapeutic targets for pain and fear-related disorders.
The numbers in context
MJN110 increased 2-AG levels in ACC and attenuated FCA. AM630 (CB2 antagonist) blocked MJN110's effect. AM251 (CB1 antagonist) did not alter MJN110's effect. CB1 and CB2 mRNA confirmed in ACC.
How the study worked
Male rats underwent fear conditioning (arena paired with footshock) followed by formalin-evoked pain testing. Microinjection of MGL inhibitor MJN110, CB2 antagonist AM630, or CB1 antagonist AM251 into the anterior cingulate cortex. 2-AG levels confirmed via mass spectrometry.
What this study cannot tell us
Animal model; male rats only; fear-conditioned analgesia is one specific form of endogenous pain suppression; pharmacological specificity of tools used.
How to read the evidence
Single animal study with clean pharmacological dissection of receptor subtypes.
When this study was published
Published in 2020.
The bigger picture
The finding that CB2 (not CB1) receptors mediate this effect in a cortical brain region is surprising, as CB2 was traditionally considered a peripheral immune receptor. This expands understanding of CB2's role in the brain.
Questions still open
- Could CB2-targeted drugs modulate pain processing in humans? What role does 2-AG play in other cortical regions involved in pain?
Common questions
What is fear-conditioned analgesia?
Why is the CB2 receptor finding surprising?
Read the original research
Attenuation of fear-conditioned analgesia in rats by monoacylglycerol lipase inhibition in the anterior cingulate cortex: Potential role for CB2 receptors.
British journal of pharmacology, 177(10), 2240-2255
Citation
Corcoran, Louise; Mattimoe, Darragh; Roche, Michelle; Finn, David P. (2020). Attenuation of fear-conditioned analgesia in rats by monoacylglycerol lipase inhibition in the anterior cingulate cortex: Potential role for CB2 receptors.. British journal of pharmacology, 177(10), 2240-2255. https://doi.org/10.1111/bph.14976
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