Chronic nicotine exposure elicits pain hypersensitivity through activation of dopaminergic projections to anterior cingulate cortex.
Br J Anaesth
; 132(4): 735-745, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38336518
ABSTRACT
BACKGROUND:
Cigarette smoking is commonly reported among chronic pain patients in the clinic. Although chronic nicotine exposure is directly linked to nociceptive hypersensitivity in rodents, underlying neurobiological mechanisms remain unknown.METHODS:
Multi-tetrode recordings in freely moving mice were used to test the activity of dopaminergic projections from the ventral tegmental area (VTA) to pyramidal neurones in the anterior cingulate cortex (ACC) in chronic nicotine-treated mice. The VTAâACC dopaminergic pathway was inhibited by optogenetic manipulation to detect chronic nicotine-induced allodynia (pain attributable to a stimulus that does not normally provoke pain) assessed by von Frey monofilaments (force units in g).RESULTS:
Allodynia developed concurrently with chronic (28-day) nicotine exposure in mice (0.36 g [0.0141] vs 0.05 g [0.0018], P<0.0001). Chronic nicotine activated dopaminergic projections from the VTA to pyramidal neurones in the ACC, and optogenetic inhibition of VTA dopaminergic terminals in the ACC alleviated chronic nicotine-induced allodynia in mice (0.06 g [0.0064] vs 0.28 g [0.0428], P<0.0001). Moreover, optogenetic inhibition of Drd2 dopamine receptor signalling in the ACC attenuated nicotine-induced allodynia (0.07 g [0.0082] vs 0.27 g [0.0211], P<0.0001).CONCLUSIONS:
These findings implicate a role of Drd2-mediated dopaminergic VTAâACC pathway signalling in chronic nicotine-elicited allodynia.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Giro do Cíngulo
/
Nicotina
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article