Miyahara Kenichiro, Nishimaru Hiroshi, Matsumoto Jumpei, Setogawa Tsuyoshi, Taguchi Toru, Ono Taketoshi, Nishijo Hisao
System Emotional Science, Faculty of Medicine, University of Toyama, Toyama, Japan.
Department of Physical Therapy, Faculty of Rehabilitation, Niigata University of Health and Welfare, Niigata, Japan.
Front Pain Res (Lausanne). 2021 Feb 26;2:627860. doi: 10.3389/fpain.2021.627860. eCollection 2021.
Fibromyalgia (FM) presents as chronic systemic pain, which might be ascribed to central sensitization, in which pain information processing is amplified in the central nervous system. Since patients with FM display elevated gamma oscillations in the pain matrix and parvalbumin (PV)-positive neurons play a critical role in induction of gamma oscillations, we hypothesized that changes in PV-positive neurons are involved in hyperalgesia in fibromyalgia. In the present study, to investigate a role of PV-positive neurons in neuropathic pain, mice received reserpine administration for 3 consecutive days as an animal model of FM (RES group), while control mice received vehicle injections in the same way (VEH group). The mice were subjected to hot-plate and forced swim tests, and immuno-stained PV-positive neurons were counted in the pain matrix. We investigated relationships between PV-positive neuron density in the pain matrix and pain avoidance behaviors. The results indicated that the mice in the RES group showed transient bodyweight loss and longer immobility time in the forced swim test than the mice in the VEH group. In the hot-plate test, the RES group showed shorter response latencies and a larger number of jumps in response to nociceptive thermal stimulus than the VEH group. Histological examination indicated an increase in the density of PV-positive neurons in the primary somatosensory cortex (S1) in the RES group. Furthermore, response latencies to the hot-plate were significantly and negatively correlated with the density of PV-positive neurons in the S1. These results suggest a critical role for PV-positive neurons in the S1 to develop hyperalgesia in FM.
纤维肌痛（FM）表现为慢性全身性疼痛，这可能归因于中枢敏化，即疼痛信息处理在中枢神经系统中被放大。由于FM患者在疼痛矩阵中显示出γ振荡升高，且小白蛋白（PV）阳性神经元在γ振荡的诱导中起关键作用，我们推测PV阳性神经元的变化与纤维肌痛的痛觉过敏有关。在本研究中，为了探究PV阳性神经元在神经性疼痛中的作用，将小鼠连续3天给予利血平作为FM动物模型（RES组），而对照小鼠以相同方式给予溶剂注射（VEH组）。对小鼠进行热板和强迫游泳试验，并对疼痛矩阵中免疫染色的PV阳性神经元进行计数。我们研究了疼痛矩阵中PV阳性神经元密度与疼痛回避行为之间的关系。结果表明，RES组小鼠在强迫游泳试验中出现短暂体重减轻，且不动时间比VEH组小鼠长。在热板试验中，RES组小鼠对伤害性热刺激的反应潜伏期更短，跳跃次数更多。组织学检查表明，RES组小鼠初级体感皮层（S1）中PV阳性神经元的密度增加。此外，热板反应潜伏期与S1中PV阳性神经元的密度呈显著负相关。这些结果表明，S1中的PV阳性神经元在FM中痛觉过敏的发生中起关键作用。
