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.

CHRONIC ETHANOL EXPOSURE INDUCES NEUROPATHIC PAIN IN MICE BY PROMOTING NEUROINFLAMMATION / Vittoria Borgonetti, Amanda Roberts, Nicoletta Galeotti, Marisa Roberto. - In: PHARMADVANCES. - STAMPA. - (2021), pp. 50-51. ((Intervento presentato al convegno The 40th Congress of the Italian Pharmacological Society (SIF)-THE SCIENTIFIC VALUE AND APPROPRIATE USE OF DRUGS.

CHRONIC ETHANOL EXPOSURE INDUCES NEUROPATHIC PAIN IN MICE BY PROMOTING NEUROINFLAMMATION

Vittoria Borgonetti;Nicoletta Galeotti;
2021

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.
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The 40th Congress of the Italian Pharmacological Society (SIF)-THE SCIENTIFIC VALUE AND APPROPRIATE USE OF DRUGS
Vittoria Borgonetti, Amanda Roberts, Nicoletta Galeotti, Marisa Roberto
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/1281447
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