Anandamide deficiency and heightened neuropathic pain in aged mice

Bishay, Philipp; Häussler, Annett; Lim, Hee-Young; Oertel, B.; Galve‐Roperh, Ismael; Ferreiròs, Nerea; Tegeder, Irmgard

doi:10.1016/j.neuropharm.2013.03.021

Cited by 29 publications

(28 citation statements)

References 57 publications

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“…However, animal studies reported either no effect 13,14 or an age-related increase 13,15 in FAAH activity or protein and we did not observe a significant effect of age on In conclusion, we show for the first time that FAAH activity in brain is dependent on a common gene variant and that genotyping for FAAH rs324420 variants during [ 11 C]CURB/PET will allow better interpretation of data.…”

Section: Discussioncontrasting

confidence: 48%

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [¹¹C]CURB

Boileau

Tyndale

Williams

et al. 2015

J Cereb Blood Flow Metab

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The common functional single-nucleotide polymorphism (rs324420, C385A) of the endocannabinoid inactivating enzyme fatty acid amide hydrolase (FAAH) has been associated with anxiety disorder relevant phenotype and risk for addictions. Here, we tested whether the FAAH polymorphism affects in vivo binding of the FAAH positron emission tomography (PET) probe [11 C]CURB ([ 11 C-carbonyl]-6-hydroxy-[1,10-biphenyl]-3-yl cyclohexylcarbamate (URB694)). Participants (n = 24) completed one [ 11 C]CURB/PET scan and were genotyped for rs324420. Relative to C/C (58%), A-allele carriers (42%) had 23% lower [11 C]CURB binding (λk 3 ) in brain. We report evidence that the genetic variant rs324420 in FAAH is associated with measurable differences in brain FAAH binding as per PET [ 11 C]CURB measurement.

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Section: Discussioncontrasting

confidence: 48%

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [¹¹C]CURB

Boileau

Tyndale

Williams

et al. 2015

J Cereb Blood Flow Metab

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“…A single i.p. injection of R-flurbiprofen during the flare of EAE caused a strong rise of ethanolamide endocannabinoids in plasma, which does not occur in mice without EAE (Bishay et al, 2013) suggesting that EAE increases the endocannabinoid-rising capacity of R-flurbiprofen.…”

Section: Embo Molecular Medicinementioning

confidence: 94%

“…Analysis of anandamide (AEA), palmitoylethanolamide (PEA), 1 and 2-arachidonoylglycerol (1+2-AG) and oleoylethanolamide (OEA) was done as described (Bishay et al, 2013). Briefly, tissue pieces of approximately 2 mg were weighed, homogenized and extracted by liquid-liquid extraction, and the reconstituted samples were analyzed for endocannabinoids.…”

Section: Analysis Of Endocannabinoidsmentioning

confidence: 99%

“…Under oxidative stress conditions, it reduced nitrite/nitrate levels and lipid peroxidation in the brain and enhanced the release of the anti-inflammatory interleukin-10 (Lopez- Villodres et al, 2011Villodres et al, , 2012. The beneficial effects of the drug may be partly lost in the aging brain (Bishay et al, 2013), and ultimately, its development was discontinued for Alzheimer's disease because efficacy in clinical phase III trials was insufficient (Green et al, 2009). This also holds true for another indication, prostate cancer, for which it was studied based on pre-clinical studies in the TRAMP mouse prostate cancer model, in which R-flurbiprofen was able to reduce the incidence of prostate tumors and metastases (Wechter et al, 2000).…”

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confidence: 99%

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R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice

Schmitz

Bruin

Bishay

et al. 2014

Journal of Neuroimmunology

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“…Indeed, animal models show that aged mice are at a higher risk of developing neuropathic pain following a spared nerve injury (Bishay et al., 2013), and aged rats suffer significantly longer from injury‐induced thermal hyperalgesia (Lovell, Novak, Stuesse, Cruce, & Crisp, 2000) and tactile allodynia (Crisp, Giles, Cruce, McBurney, & Stuesse, 2003). Interestingly, some rodent pain models also point to increased pain sensitivity in midlife.…”

Section: Introductionmentioning

confidence: 99%

Differential aging‐related changes in neurophysiology and gene expression in IB4‐positive and IB4‐negative nociceptive neurons

et al. 2018

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SummaryDespite pain prevalence altering with age, the effects of aging on the properties of nociceptors are not well understood. Nociceptors, whose somas are located in dorsal root ganglia, are frequently divided into two groups based on their ability to bind isolectin B4 (IB4). Here, using cultured neurons from 1‐, 3‐, 5‐, 8‐, 12‐, and 18‐month‐old mice, we investigate age‐dependent changes in IB4‐positive and IB4‐negative neurons. Current‐clamp experiments at physiological temperature revealed nonlinear changes in firing frequency of IB4‐positive, but not IB4‐negative neurons, with a peak at 8 months. This was likely due to the presence of proexcitatory conductances activated at depolarized membrane potentials and significantly higher input resistances found in IB4‐positive neurons from 8‐month‐old mice. Repetitive firing in nociceptors is driven primarily by the TTX‐resistant sodium current, and indeed, IB4‐positive neurons from 8‐month‐old mice were found to receive larger contributions from the TTX‐resistant window current around the resting membrane potential. To further address the mechanisms behind these differences, we performed RNA‐seq experiments on IB4‐positive and IB4‐negative neurons from 1‐, 8‐, and 18‐month‐old mice. We found a larger number of genes significantly affected by age within the IB4‐positive than IB4‐negative neurons from 8‐month‐old mice, including known determinants of nociceptor excitability. The above pronounced age‐dependent changes at the cellular and molecular levels in IB4‐positive neurons point to potential mechanisms behind the reported increase in pain sensitivity in middle‐aged rodents and humans, and highlight the possibility of targeting a particular group of neurons in the development of age‐tailored pain treatments.

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Anandamide deficiency and heightened neuropathic pain in aged mice

Cited by 29 publications

References 57 publications

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [¹¹C]CURB

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [¹¹C]CURB

R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice

Differential aging‐related changes in neurophysiology and gene expression in IB4‐positive and IB4‐negative nociceptive neurons

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Anandamide deficiency and heightened neuropathic pain in aged mice

Cited by 29 publications

References 57 publications

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [11C]CURB

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [11C]CURB

R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice

Differential aging‐related changes in neurophysiology and gene expression in IB4‐positive and IB4‐negative nociceptive neurons

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The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [¹¹C]CURB

The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [¹¹C]CURB