Parvalbumin gates chronic pain through the modulation of firing patterns in inhibitory neurons

• 成果类型: Article
• 署名作者: Qiu, Haoyi; Miraucourt, Lois S.; Petitjean, Hugues; Xu, Mengyi; Theriault, Catherine; Davidova, Albena; Soubeyre, Vanessa; Poulen, Gaetan; Lonjon, Nicolas; Vachiery-Lahaye, Florence; Bauchet, Luc; Levesque-Damphousse, Philipa; Estall, Jennifer L.; Bourinet, Emmanuel; Sharif-Naeini, Reza
• 署名单位: McGill University; McGill University; Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Montpellier; CHU de Montpellier; Universite de Montpellier; Universite de Montreal; Institut de Recherche Clinique de Montreal (IRCM)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11146
• DOI: 10.1073/pnas.2403777121
• 发表日期: 2024-07-02
• 关键词: peripheral-nerve injury; dorsal-horn contributes; spinal-cord; neuropathic pain; gamma-oscillations; expression; interneurons; pgc-1-alpha; activation; circuits

摘要

Spinal cord dorsal horn inhibition is critical to the processing of sensory inputs, and its impairment leads to mechanical allodynia. How this decreased inhibition occurs and whether its restoration alleviates allodynic pain are poorly understood. Here, we show that a critical step in the loss of inhibitory tone is the change in the firing pattern of inhibitory parvalbumin (PV)- expressing neurons (PVNs). Our results show that PV, a calcium- binding protein, controls the firing activity of PVNs by enabling them to sustain high- frequency tonic firing patterns. Upon nerve injury, PVNs transition to adaptive firing and decrease their PV expression. Interestingly, decreased PV is necessary and sufficient for the development of mechanical allodynia and the transition of PVNs to adaptive firing. This transition of the firing pattern is due to the recruitment of calcium- activated potassium (SK) channels, and blocking them during chronic pain restores normal tonic firing and alleviates chronic pain. Our findings indicate that PV is essential for controlling the firing pattern of PVNs and for preventing allodynia. Developing approaches to manipulate these mechanisms may lead to different strategies for chronic pain relief.