A mouse model for chronic pain-induced increase in ethanol consumption

Abstract

Chronic pain conditions are often co-morbid with alcohol abuse. "Self-medication" with alcohol introduces a host of problems associated with the abuse of alcohol which over time has the potential of exacerbating the painful condition. Despite the prevalence of chronic pain being associated with alcohol abuse, rodent models which mimic the co-morbid conditions are lacking. In the present study, we model osteoarthritis (OA) in C57BL/6J mice by surgically destabilizing the medial meniscus (DMM). Sham operated mice served as controls. Thirteen weeks after surgery, DMM but not sham operated mice exhibited pronounced incapacitance of the surgicallymanipulated hindlimb compared to the non-surgically manipulated hindlimb. At this time, the mice were exposed to the two-bottle ethanol choice, beginning with 2.5% with a gradual increasing to 20%. Compared to sham controls, DMM mice consumed more EtOH and preferred EtOH over water at the 20% EtOH concentration. Histological analysis verified that the DMM mice exhibited significant damage to the articular cartilage and osteophyte growth compared to sham controls and these measures of the severity of OA correlated with the amount of ethanol * Correspondence: Dr. George R. Breese, Bowles Center for Alcohol Studies, Thurston Bowles Building, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7178, USA. Declaration of interestThe authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. intake. Thus, the combination of the DMM model of OA with the enhanced two-bottle ethanol choice is a potential preclinical approach in mice by which the basis of the co-morbid association of alcohol abuse and chronic pain conditions can be explored. HHS Public Access

Reduced sensitivity to ethanol and excessive drinking in a mouse model of neuropathic pain

“…The first study is in agreement with our findings, reporting no alterations in alcohol intake or preference after the induction of chronic inflammatory pain in both male and female mice . Another study used a mouse model of osteoarthritis and showed increased voluntary alcohol consumption . These discrepancies in study outcome could be explained by the fact that depending on the pain condition, the prevalence of alcohol abuse ranges from 2% to 22%.…”

“…One study used a sciatic chronic pain mouse model and showed that mice drank more under intermittent ethanol intake schedule using the drinking in the dark model, while pain responses were not attenuated by ethanol consumption . Another study found also increased alcohol consumption in a model of osteoarthritis in mice . However, no increase in alcohol consumption in mice after Complete Freund's Adjuvant (CFA) injection was observed .…”

Effect Of Inflammatory Pain On Alcohol-Induced Dopamine Release In The Nucleus Accumbens: Behavioural Implications In Rat Models

“…As a consequence, pain may also, in some way, have an effect on ethanol reinforcing properties and relapse. To this extent, some preclinical research has recently shown an increase in voluntary ethanol consumption in pain-suffering male mice when compared to pain-free groups [4,39].…”

“…It also is important to note that pain-induced changes may differently affect addictive behaviors depending on the different stages of the AUD. In fact, previous studies using an intermittent two-bottle choice paradigm show that pain induction prior to alcohol exposure significantly increases total intake in male mice [4,39] and it may be plausible that pain increases alcohol intake during acquisition without modifying the magnitude of ADE. On the other hand, we have only tested male rats based in the previous data reported [4,39] and, it could be plausible that relapse-like behavior may be expressed differentially depending on the sex.…”

“…In fact, previous studies using an intermittent two-bottle choice paradigm show that pain induction prior to alcohol exposure significantly increases total intake in male mice [4,39] and it may be plausible that pain increases alcohol intake during acquisition without modifying the magnitude of ADE. On the other hand, we have only tested male rats based in the previous data reported [4,39] and, it could be plausible that relapse-like behavior may be expressed differentially depending on the sex. In any case, our data highlight the necessity of finding the appropriate animal model that reflects the existing clinical evidence and allows us to study the alcohol-related behavioral implication of pain-induced alterations of the MCLS.…”