2. Academic Validation
  3. KCNQ Channels in the Mesolimbic Reward Circuit Regulate Nociception in Chronic Pain in Mice

KCNQ Channels in the Mesolimbic Reward Circuit Regulate Nociception in Chronic Pain in Mice

  • Neurosci Bull. 2021 May;37(5):597-610. doi: 10.1007/s12264-021-00668-x.
Hao-Ran Wang  # 1 2 3,  Su-Wan Hu  # 1 2,  Song Zhang  # 1 2 4,  Yu Song 1 2,  Xiao-Yi Wang 1 2,  Lei Wang 1 2,  Yang-Yang Li 1 2,  Yu-Mei Yu 1 2,  He Liu 1 2 5,  Di Liu 1 2,  Hai-Lei Ding 1 2,  Jun-Li Cao 6 7 8
Affiliations

Affiliations

  • 1 Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, 221004, China.
  • 2 Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, 221004, China.
  • 3 Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing, 210029, China.
  • 4 Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200000, China.
  • 5 Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China.
  • 6 Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, 221004, China. [email protected].
  • 7 Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, 221004, China. [email protected].
  • 8 Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China. [email protected].
  • # Contributed equally.
PMID: 33900570 DOI: 10.1007/s12264-021-00668-x
Abstract

Mesocorticolimbic dopaminergic (DA) neurons have been implicated in regulating nociception in chronic pain, yet the mechanisms are barely understood. Here, we found that chronic constructive injury (CCI) in mice increased the firing activity and decreased the KCNQ channel-mediated M-currents in ventral tegmental area (VTA) DA neurons projecting to the nucleus accumbens (NAc). Chemogenetic inhibition of the VTA-to-NAc DA neurons alleviated CCI-induced thermal nociception. Opposite changes in the firing activity and M-currents were recorded in VTA DA neurons projecting to the medial prefrontal cortex (mPFC) but did not affect nociception. In addition, intra-VTA injection of retigabine, a KCNQ opener, while reversing the changes of the VTA-to-NAc DA neurons, alleviated CCI-induced nociception, and this was abolished by injecting exogenous BDNF into the NAc. Taken together, these findings highlight a vital role of KCNQ channel-mediated modulation of mesolimbic DA activity in regulating thermal nociception in the chronic pain state.

Keywords

Brain-derived neurotrophic factor; Chronic neuropathic pain; KCNQ; Mesocorticolimbic system; Nociception; Retigabine; Ventral tegmental area.

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