Department of Anesthesiology, Huashan Hospital North, Fudan University, Shanghai 201907, China.
Department of Anesthesiology, Wannan Medical College First Affiliated Hospital, Yijishan Hospital, Wuhu 241004, China.
J Clin Neurosci. 2022 Jan;95:180-187. doi: 10.1016/j.jocn.2021.11.019. Epub 2021 Dec 17.
This study aims to observe the effects of direct suppression of the parabrachial nucleus (PBN) on chronic neuropathic pain (CNP) and CNP-related behaviors in mice.
A CNP model was established using partial sciatic nerve ligation (PSNL) in mice. Two groups were established: the experimental (PSNL) group and the control (sham) group. An assessment of PBN-region c-Fos expression was conducted following von Frey hair stimulation in the PSNL group and the sham group, and the effects of pain induction were detected using behavioral experiments. The PBN activity of the mice with CNP was manipulated using the designer receptors exclusively activated by designer drugs method. Effective and empty virus groups were used to study the effects of PBN activity inhibition on the pain threshold and pain-related behavior in mice with CNP.
The mechanical pain threshold (MPT) of the mice in the PSNL group was significantly lower than in the sham group. After von Frey stimulation, the c-Fos-positive, PBN-region neurons in the PSNL group were increased compared with the sham group. The central distance in the open field test and the time spent in the central area were lower in the PSNL group than in the sham group. The mice in the PSNL group had a lower duration and fewer entries in the open arm of the elevated plus-maze than the mice in the sham group. There was no difference in immobility time between the PSNL group and the sham group. PBN activity inhibition in mice with CNP did not affect their MPT or anxiety-like behavior.
CNP can induce anxiety-like behavior and increase PBN-induced pain in mice. However, direct inhibition of the PBN neuron activity alone cannot improve CNP or CNP-related behavior.
本研究旨在观察直接抑制臂旁核(PBN)对慢性神经病理性疼痛(CNP)及相关行为的影响。
采用部分坐骨神经结扎(PSNL)建立 CNP 模型,在 PSNL 组和假手术(sham)组中观察 von Frey 毛发刺激后 PBN 区 c-Fos 表达的变化,并进行行为学检测,以评估疼痛诱导的影响。采用 Designer Receptors Exclusively Activated by Designer Drugs(DREADD)技术对 CNP 小鼠的 PBN 活性进行干预,有效和空载病毒组用于研究抑制 PBN 活性对 CNP 小鼠痛阈和痛相关行为的影响。
PSNL 组小鼠的机械痛阈(MPT)明显低于 sham 组。von Frey 刺激后,PSNL 组 PBN 区 c-Fos 阳性神经元较 sham 组增加。与 sham 组相比,PSNL 组在旷场试验中的中央距离和中央区域停留时间减少,高架十字迷宫试验中进入开放臂的持续时间和次数减少,而两组的不动时间无差异。抑制 CNP 小鼠的 PBN 活性并不影响其 MPT 或焦虑样行为。
CNP 可诱导焦虑样行为并增加小鼠的 PBN 诱导性疼痛,而单独直接抑制 PBN 神经元活性不能改善 CNP 或 CNP 相关行为。