Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice DOI Creative Commons
Cristina Miliano, Yan Dong,

M Proffit

и другие.

Опубликована: Ноя. 11, 2024

Abstract Alcohol use disorder (AUD) affects millions of people and represents a significant health economic burden. Pain frequently under-treated aspect hyperkatifeia during alcohol withdrawal, yet to date no drugs have received FDA approval for the treatment this indication in AUD patients. This study aims evaluate potential targeting bioactive lipid signaling pathways as therapeutic approach treating withdrawal-related pain. We utilized chronic intermittent ethanol (CIE) vapor exposure model C57BL/6J mice both sexes establish dependence, demonstrated that CIE developed robust tactile allodynia thermal hyperalgesia withdrawal was independent prior blood levels. Next, we evaluated four their efficacy reversing abstinence from using cross-over design included FDA-approved naltrexone well commercially available inhibitors inflammatory enzymes including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), 15-Lipoxygenase (LOX). None these compounds produced benefit established CIE-induced allodynia, despite attenuating pain-like behaviors at doses other pain models. Additionally, assessed plasma endocannabinoid levels withdrawal. found there is an inherent sex difference endogenous anti-inflammatory tone naive affected endocannabinoids female only. These findings underscore need better understand driving causes induced develop novel approaches mitigate

Язык: Английский

Apremilast reduces co-occurring alcohol drinking and mechanical allodynia and regulates central amygdala GABAergic transmission DOI Creative Commons
Valentina Vozella, Vittoria Borgonetti, Bryan Cruz

и другие.

JCI Insight, Год журнала: 2025, Номер 10(8)

Опубликована: Апрель 21, 2025

The FDA-approved phosphodiesterase type 4 (PDE4) inhibitor, apremilast, has been recently investigated as a pharmacotherapy for alcohol use disorder (AUD) with promising efficacy in rodent models and humans. However, apremilast's effects on mechanical allodynia associated AUD well distinct responses of this drug between males females are understudied. present study examined the behavioral electrophysiological apremilast Marchigian Sardinian alcohol-preferring (msP) rats their Wistar counterparts. We used 2-bottle choice (2-BC) drinking procedure tested sensitivity across our regimen. Spontaneous inhibitory GABA-mediated postsynaptic currents from central nucleus amygdala (CeA) following application were subset using ex vivo electrophysiology. Transcript levels Pde4a or -4b subtypes assessed modulation by alcohol. Apremilast reduced both strains rats. immediately after drinking, persisting into early late abstinence. increased GABAergic transmission CeA slices alcohol-exposed Wistars but not msP rats, suggesting neuroadaptations msPs excessive allodynia. Pde4 subtype transcript These results suggest that alleviates co-occurring pain sensitivity, they further confirm PDE4's role pain-associated AUD.

Язык: Английский

Процитировано

0
Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice DOI
Cristina Miliano,

Yanbin Dong,

M Proffit

и другие.

Neuropharmacology, Год журнала: 2025, Номер unknown, С. 110502 - 110502

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice DOI Creative Commons
Cristina Miliano, Yan Dong,

M Proffit

и другие.

Опубликована: Ноя. 11, 2024

Abstract Alcohol use disorder (AUD) affects millions of people and represents a significant health economic burden. Pain frequently under-treated aspect hyperkatifeia during alcohol withdrawal, yet to date no drugs have received FDA approval for the treatment this indication in AUD patients. This study aims evaluate potential targeting bioactive lipid signaling pathways as therapeutic approach treating withdrawal-related pain. We utilized chronic intermittent ethanol (CIE) vapor exposure model C57BL/6J mice both sexes establish dependence, demonstrated that CIE developed robust tactile allodynia thermal hyperalgesia withdrawal was independent prior blood levels. Next, we evaluated four their efficacy reversing abstinence from using cross-over design included FDA-approved naltrexone well commercially available inhibitors inflammatory enzymes including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), 15-Lipoxygenase (LOX). None these compounds produced benefit established CIE-induced allodynia, despite attenuating pain-like behaviors at doses other pain models. Additionally, assessed plasma endocannabinoid levels withdrawal. found there is an inherent sex difference endogenous anti-inflammatory tone naive affected endocannabinoids female only. These findings underscore need better understand driving causes induced develop novel approaches mitigate

Язык: Английский

Процитировано

0