正、负性情绪分别发挥抑制和促进疼痛的作用，而情绪与奖赏密切相关。实际奖赏>预期（正性奖赏预测误差）和无预期奖赏，实际奖赏<预期（负性奖赏预测误差）和无预期厌恶刺激可分别引起正、负性情绪。但对奖赏中心VTA及其神经通路对痛感觉及相关负性情绪的影响各报道不一，对负性事件引起抗奖赏中心外侧缰核LHb高活性的机制亦不清楚。课题组预实验发现无预期奖赏减轻炎症热痛敏行为；慢性痛降低LHb中GABA递质含量，核团注射其受体激动剂减轻痛感觉及相关负性情绪。据此我们提出假说：内、外侧VTA亚区以通路特异的方式影响痛感觉及相关负性情绪；去抑制机制参与LHb高活性并促进疼痛，通过加强其抑制性输入，可达到镇痛目的。我们将围绕上述假说，综合应用在体钙成像，光遗传学等方法，阐明VTA和LHb及其相关神经通路在痛感觉及相关负性情绪中的作用。该研究对阐明情绪调控疼痛的生物学机制，发掘新的促痛或抑痛的中枢通路具有重要意义。

Positive and negative emotions can facilitate and inhibit pain transmission, respectively. Reward is closely related to the production of positive and negative emotions. When actual reward is better than expected or unexpected rewarding stimuli were received, positive emotions were produced. On the contrary, when actual reward is worse than expected or unexpected aversive stimuli were received, negative emotions were produced. Ventral tegmental area (VTA) is activated by the rewarding stimuli and is regarded as the reward center. However, there is no consensus on the role of VTA and the connected-neural circuits on nociceptive processing and pain-related negative emotions. On the other hand, lateral habenua (LHb) is activated by the aversive stimuli and is regarded as the anti-reward center. The mechanisms of LHb hyperactivity during negative events remain unknown. Our preliminary data indicate that thermal hyperalgesia is attenuated when rats received unexpected rewarding stimuli during inflammatory pain. The content of inhibitory neurotransmitter GABA in LHb is reduced during inflammatory pain. Intra-LHb injection of muscimol, a GABAa receptor agonist, alleviates pain-like behavior, and reduces formalin-induced conditioned place aversion (CPA) and anxiety-like behavior. Based on these data, we propose the following hypothesis. The medial and lateral VTA modulate the nociceptive processing and pain-related negative emotions in a neural circuit-specific pathway. Disinhibition contributes to the hyperactivity of LHb and is involved in the facilitation of pain transmission by LHb. Thus, enhancing the inhibitory input of LHb can inhibit the activation of LHb and subsequently obtain the analgesic effect. Our study will focus on the above hypothesis and elucidate the role of VTA and LHb and the-related neural circuits in nociceptive processing and pain-related negative emotions using combined approaches, including in vivo calcium imaging technique, optogenetics, morphological and electrophysiological methods and behavioral tests. This project is of significance for elucidating the biological mechanisms for the modulation of pain by emotions and helps to identify the new neural circuits facilitating or inhibiting pain transmission in the brain.