The prefrontal cortical endocannabinoid system modulates fear-pain interactions in a subregion-specific manner

British Journal of Pharmacology
Kieran ReaDavid P Finn

Abstract

The emotional processing and coordination of top-down responses to noxious and conditioned aversive stimuli involves the medial prefrontal cortex (mPFC). Evidence suggests that subregions of the mPFC [infralimbic (IfL), prelimbic (PrL) and anterior cingulate (ACC) cortices] differentially alter the expression of contextually induced fear and nociceptive behaviour. We investigated the role of the endocannabinoid system in the IfL, PrL and ACC in formalin-evoked nociceptive behaviour, fear-conditioned analgesia (FCA) and conditioned fear in the presence of nociceptive tone. FCA was modelled in male Lister-hooded rats by assessing formalin-evoked nociceptive behaviour in an arena previously paired with footshock. The effects of intra-mPFC administration of AM251 [cannabinoid type 1 (CB1 ) receptor antagonist/inverse agonist], URB597 [fatty acid amide hydrolase (FAAH) inhibitor] or URB597 + AM251 on FCA and freezing behaviour were assessed. AM251 attenuated FCA when injected into the IfL or PrL and reduced contextually induced freezing behaviour when injected intra-IfL but not intra-PrL or intra-ACC. Intra-ACC administration of AM251 alone or in combination with URB597 had no effect on FCA or freezing. URB597 attenuated FCA and fre...Continue Reading

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Citations

Oct 2, 2019·Journal of Neurochemistry·Nicholas AtwalChristopher W Vaughan
Apr 30, 2019·British Journal of Pharmacology·Stephen P H Alexander, Francisco Molina-Holgado
Feb 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jessica C GasparDavid P Finn
Nov 4, 2020·Neurotoxicity Research·Karla Chavira-RamosAna Laura Colín-González
Oct 19, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jia SunDa-Wei Ye

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