Chronic Ethanol Exposure Induces Neuropathic Pain in Mice by Promoting Neuroinflammation
Year: 2021
Type: conference-paper
Abstract: ACKGROUND: Alcohol use disorder (AUD) is defined by the emergence of negative affective symptoms during withdrawal. In particular, chronic or excessive alcohol consumption results in a hypersensitivity condition, that is considered a negative reinforcement process, facilitating AUD progression. The mechanisms responsible for the observed increasing of chronic pain associated with chronic alcohol consumption are still unknown. Neuroinflammation is a key contributor to alcohol reinforcement and it is well known to play a key role also in the pathogenesis of neuropath- ic pain. Thus, the aim of this project was to evaluate the development of neuropathy in a mouse model of alcohol dependence, and to investigate the role of neuroinflammation in this chronic condition. METHODS: We used the chronic-intermit- tent ethanol two-bottle choice (2BC-CIE) par- adigm to generate ethanol-dependent (Dep) mice exhibiting escalations in alcohol drink- ing after CIE vapor exposure, non-dependent (Non-Dep) mice with the same voluntary alco- hol drinking history and ethanol-naive (naive) control C57bl/6J mice. Von Frey filaments were used to measure the mechanical allodynia in naive, Non-Dep and Dep mice during the 72 h of withdrawal and immediately after 2-bottle choice test. In vitro evaluations of microglia ac- tivation in spinal cord tissue of mice were also conducted. RESULTS: A significant drinking escalation in the Dep group was observed in both sexes, compared to Non-Dep mice. Both male and female Dep mice developed a strong mechan- ical allodynia during the 72 h of withdrawal, which was completely reverted immediately after voluntary 2BC test. Also, the Non-Dep group showed a long-lasting increase of sensitivity compared to the naive group, which was not reverted by self-alcohol administration. An increase of microglia activation markers in the spinal cord tissue of 2BC-CIE were observed. CONCLUSIONS: These results suggested that chronic alcohol exposure induced abstinencerelated hyperalgesia in Dep mice, com- pared to Non-Dep and naive mice. Moreover, in our model we observed that increased hypersensitivity occurs in 40% and 50% of Dep male and female mice, respectively, compared to the naive group, highlighting that the chronic consumption of alcohol may also induces a direct alcohol-related neuropathy. Neuroinflammation, and in particular the role of microglia activation, may represent an interesting target for the management of this chronic pain condition.
Authors: Vittoria Borgonetti, Amanda Roberts, Nicoletta Galeotti, Marisa Roberto
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6980585488