A role for the ventral hippocampal endocannabinoid system in fear-conditioned analgesia and fear responding in the presence of nociceptive tone in rats

Ford, Gemma K.; Kieran, Siobhan; Dolan, Kenneth; Harhen, Brendan; Finn, David P.

doi:10.1016/j.pain.2011.07.014

Cited by 29 publications

(44 citation statements)

References 83 publications

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“…For bilateral intra‐PrL, intra‐IfL and intra‐ACC microinjections, AM251 and URB597 were diluted to a concentration of 2 and 0.1 mM in 100% DMSO VEH, respectively, while the combination was prepared by adding equal volumes of the stock 4 mM AM251 and 0.2 mM URB597. These doses of URB597 and AM251 are based on previous work carried out by our laboratory and evidence from the literature in rat models of pain and fear (Laviolette and Grace, ; de Novellis et al ., ; Lisboa et al ., ; Ebrahimzadeh and Haghparast, ; Ford et al ., ; Olango et al ., ; Freitas et al ., ; Rea et al ., ). A solution of 2.5% formalin (Sigma‐Aldrich) was prepared from a 37% stock solution diluted with 0.9% sterile saline.…”

Section: Methodsmentioning

confidence: 98%

“…The video feed was recorded onto DVD for 30 min. The 30–60 min post‐formalin interval was chosen on the basis of previous studies demonstrating that formalin‐evoked nociceptive behaviour is stable over this time period, is endocannabinoid mediated and is subject to supraspinal modulation (Finn et al ., ; Ford et al ., ; Olango et al ., ; Rea et al ., ; Roche et al ., ).…”

Section: Methodsmentioning

confidence: 98%

“…Moreover, we and others have demonstrated a key role for the endocannabinoid system in FCA (Finn et al ., ; Finn et al ., ; Roche et al ., ; Butler et al ., ; Ford and Finn, ; Butler and Finn, ; Ford et al ., ; Olango et al ., ; Rea et al ., ; Olango et al ., ; Corcoran et al ., ) and unconditioned stress‐induced analgesia (Hohmann et al ., ; Suplita et al ., ; Connell et al ., ; Guindon and Hohmann, ). These studies have highlighted the importance of the endocannabinoid system in discrete brain regions including the amygdala (Rea et al ., ), hippocampus (Ford et al ., ) and periaqueductal grey (Olango et al ., ), all of which are connected anatomically to the mPFC. Components of the endocannabinoid system, including CB 1 receptors and the anandamide‐catabolizing enzyme fatty acid amide hydrolase (FAAH), are highly expressed in the mPFC (Herkenham et al ., ; Mailleux and Vanderhaeghen, ; Tsou et al ., ; Egertova et al ., ).…”

Section: Introductionmentioning

confidence: 98%

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

Rea

McGowan

Corcoran

et al. 2018

British J Pharmacology

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Section: Methodsmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

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

Rea

McGowan

Corcoran

et al. 2018

British J Pharmacology

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“…Brains from the young and aged, vehicle or URB597 treated rats were removed rapidly and the cerebellum was gross-dissected (average weight of tissue samples = 158.26 mg), snap-frozen on dry ice and stored at -80 0 C prior to extraction and determination of the concentrations of the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) and the related N -acylethanolamines N -palmitoyl ethanolamide (PEA) and N -oleoyl ethanolamide (OEA) by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) as described previously [29,30]. Each tissue sample was first homogenized in 400 μL 100% acetonitrile containing known fixed amounts of deuterated internal standards (0.014 nmol AEA-d8, 0.48 nmol 2-AG-d8, 0.016 nmol PEA-d4, 0.015 nmol OEA-d2).…”

Section: Methodsmentioning

confidence: 99%

The fatty acid amide hydrolase inhibitor URB597 exerts anti-inflammatory effects in hippocampus of aged rats and restores an age-related deficit in long-term potentiation

Murphy

Cowley

Blau

et al. 2012

J Neuroinflammation

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BackgroundSeveral factors contribute to the deterioration in synaptic plasticity which accompanies age and one of these is neuroinflammation. This is characterized by increased microglial activation associated with increased production of proinflammatory cytokines like interleukin-1β (IL-1β). In aged rats these neuroinflammatory changes are associated with a decreased ability of animals to sustain long-term potentiation (LTP) in the dentate gyrus. Importantly, treatment of aged rats with agents which possess anti-inflammatory properties to decrease microglial activation, improves LTP. It is known that endocannabinoids, such as anandamide (AEA), have anti-inflammatory properties and therefore have the potential to decrease the age-related microglial activation. However, endocannabinoids are extremely labile and are hydrolyzed quickly after production. Here we investigated the possibility that inhibiting the degradation of endocannabinoids with the fatty acid amide hydrolase (FAAH) inhibitor, URB597, could ameliorate age-related increases in microglial activation and the associated decrease in LTP.MethodsYoung and aged rats received subcutaneous injections of the FAAH inhibitor URB597 every second day and controls which received subcutaneous injections of 30% DMSO-saline every second day for 28 days. Long-term potentiation was recorded on day 28 and the animals were sacrificed. Brain tissue was analyzed for markers of microglial activation by PCR and for levels of endocannabinoids by liquid chromatography coupled to tandem mass spectrometry.ResultsThe data indicate that expression of markers of microglial activation, MHCII, and CD68 mRNA, were increased in the hippocampus of aged, compared with young, rats and that these changes were associated with increased expression of the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-α (TNFα) which were attenuated by treatment with URB597. Coupled with these changes, we observed an age-related decrease in LTP in the dentate gyrus which was partially restored in URB597-treated aged rats. The data suggest that enhancement of levels of endocannabinoids in the brain by URB597 has beneficial effects on synaptic function, perhaps by modulating microglial activation.

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“…Like SIA, it has been shown that FCA in rats is fully attenuated by intra-dlPAG injection of the CB 1 receptor antagonist/inverse agonist rimonabant and is associated with increased tissue levels of AEA in this PAG column (Olango et al, 2012). The ventral hippocampus is another locus of endocannabinoid-mediated FCA in rats (Ford et al, 2011). Additional work in mice has suggested that interactions between the endocannabinoid system and the cholecystokininergic (CCK) system (particularly CCK 2 receptors) are important for expression of an opioid-dependent form of unconditioned SIA (Kurrikoff et al, 2008).…”

Section: The Ec System and Stress-induced Modulation Of Painmentioning

confidence: 99%

The cannabinoid system and pain

et al. 2017

Self Cite

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Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics, representing an enormous clinical, societal, and economic burden. Existing pain medications have significant limitations and adverse effects including tolerance, dependence, gastrointestinal dysfunction, cognitive impairment, and a narrow therapeutic window, making the search for novel analgesics ever more important. In this article, we review the role of an important endogenous pain control system, the endocannabinoid (EC) system, in the sensory, emotional, and cognitive aspects of pain. Herein, we briefly cover the discovery of the EC system and its role in pain processing pathways, before concentrating on three areas of current major interest in EC pain research; 1. Pharmacological enhancement of endocannabinoid activity (via blockade of EC metabolism or allosteric modulation of CB1 receptors); 2. The EC System and stress-induced modulation of pain; and 3. The EC system & medial prefrontal cortex (mPFC) dysfunction in pain states. Whilst we focus predominantly on the preclinical data, we also include extensive discussion of recent clinical failures of endocannabinoid-related therapies, the future potential of these approaches, and important directions for future research on the EC system and pain.

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A role for the ventral hippocampal endocannabinoid system in fear-conditioned analgesia and fear responding in the presence of nociceptive tone in rats

Cited by 29 publications

References 83 publications

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

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

The fatty acid amide hydrolase inhibitor URB597 exerts anti-inflammatory effects in hippocampus of aged rats and restores an age-related deficit in long-term potentiation

The cannabinoid system and pain

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