Miyake Ryo, Yamanaka Manabu, Taniguchi Wataru, Nishio Naoko, Matsuyama Yuki, Ueno Takeru, Kaimochi Yuta, Nakatsuka Terumasa, Yamada Hiroshi
Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, Japan.
Pain Research Center, Kansai University of Health Sciences, Osaka, Japan.
Mol Brain. 2025 Aug 22;18(1):72. doi: 10.1186/s13041-025-01207-9.
Osteoarthritis of the knee (knee OA) causes chronic pain involving peripheral tissues, the spinal cord, and the brain. Neuropathic pain leads to changes in synaptic plasticity in the anterior cingulate cortex (ACC). However, whether such changes occur in knee OA mice and their association with exercise therapy remains unclear. Therefore, this study investigated these aspects using electrophysiological and behavioral approaches. We found no induction of pre- or post-long-term potentiation (LTP) in the ACC of knee OA mice. Application of ZD7288 and zeta inhibitory peptide (ZIP) reduced the amplitude of evoked excitatory postsynaptic currents, indicating pre-existing changes in synaptic plasticity in the ACC. Microinjection of ZD7288 and ZIP improved pain-escape and anxiety-like behaviors. Voluntary running exercise induced pre- and post-LTP and improved these behaviors in knee OA mice. Exercise therapy for knee OA may alter synaptic plasticity in the ACC, contributing to behavioral improvements.
膝关节骨关节炎（膝骨关节炎）会导致涉及外周组织、脊髓和大脑的慢性疼痛。神经性疼痛会导致前扣带回皮质（ACC）突触可塑性的变化。然而，在膝骨关节炎小鼠中是否会发生这种变化以及它们与运动疗法的关联仍不清楚。因此，本研究使用电生理和行为学方法对这些方面进行了调查。我们发现膝骨关节炎小鼠的ACC中未诱导出长时程增强（LTP）的前或后阶段。应用ZD7288和ζ抑制肽（ZIP）降低了诱发的兴奋性突触后电流的幅度，表明ACC中突触可塑性已存在变化。微量注射ZD7288和ZIP改善了逃避疼痛和焦虑样行为。自愿跑步运动诱导了LTP的前和后阶段，并改善了膝骨关节炎小鼠的这些行为。膝骨关节炎的运动疗法可能会改变ACC中的突触可塑性，从而有助于行为改善。
