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. 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 VTA→ACC 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). Allodynia developed concurrently with chronic (28-day) nicotine exposure in mice (0.36 g [0.0141] 0.05 g [0.0018], <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] 0.28 g [0.0428], <0.0001). Moreover, optogenetic inhibition of Drd2 dopamine receptor signalling in the ACC attenuated nicotine-induced allodynia (0.07 g [0.0082] 0.27 g [0.0211], <0.0001). These findings implicate a role of Drd2-mediated dopaminergic VTA→ACC pathway signalling in chronic nicotine-elicited allodynia.

中文翻译：

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慢性尼古丁暴露通过激活前扣带皮层的多巴胺能投射而引起疼痛过敏

临床上慢性疼痛患者经常吸烟。尽管慢性尼古丁暴露与啮齿动物的伤害性超敏反应直接相关，但潜在的神经生物学机制仍然未知。使用自由活动小鼠的多四极记录来测试慢性尼古丁治疗小鼠从腹侧被盖区（VTA）到前扣带皮层（ACC）锥体神经元的多巴胺能投射的活性。通过光遗传学操作抑制 VTA→ACC 多巴胺能通路，以检测由 von Frey 单丝（力单位为 g）评估的慢性尼古丁引起的异常性疼痛（由通常不会引起疼痛的刺激引起的疼痛）。小鼠慢性（28 天）尼古丁暴露同时出现异常性疼痛（0.36 g [0.0141] 0.05 g [0.0018]，<0.0001）。慢性尼古丁激活从 VTA 到 ACC 中锥体神经元的多巴胺能投射，以及 ACC 中 VTA 多巴胺能末端的光遗传学抑制减轻了小鼠中慢性尼古丁引起的异常性疼痛（0.06 g [0.0064] 0.28 g [0.0428]，<0.0001）。此外，ACC 中 Drd2 多巴胺受体信号的光遗传学抑制可减轻尼古丁引起的异常性疼痛（0.07 g [0.0082] 0.27 g [0.0211]，<0.0001）。这些发现暗示了 Drd2 介导的多巴胺能 VTA→ACC 通路信号在慢性尼古丁引起的异常性疼痛中的作用。